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Background: Hereditary spherocytosis is a rare genetic disorder of the red blood cell membrane that is characterized by anemia, jaundice, and splenomegaly; however, in the absence of family history and with unusual clinical presentation, the diagnosis might not be made until later in life. Case presentation: Here, we present a challenging case of genetically proven hereditary spherocytosis that involves the SPTB gene in a 23-year-old female patient from Ethiopia who had repeated medical visits for episodic jaundice and hepatosplenomegaly, with unusual features of conjugated hyperbilirubinemia, pancytopenia, normal reticulocyte count, and lack of family history, where the delay in diagnosis led to several complications. The patient was successfully managed with simultaneous splenectomy and cholecystectomy. Conclusion: This case underscores the importance of a thorough clinical examination, spending the time to review a case periodically without assuming the initial diagnosis is correct, and maintaining a healthy skepticism of inconsistent data to prevent misdiagnosis and mistreatment. The diagnostic delay highlights the need for increased awareness and familiarity with diagnostic modalities of hereditary spherocytosis among healthcare providers in Ethiopia. [ABSTRACT FROM AUTHOR]

Seronegative antiphospholipid syndrome (SN‐APS) is uncommon and challenging condition, which should be included in the differential diagnosis of stroke in young, since it can result in arterial thrombosis.SN‐APS is typically diagnosed by exclusion; however, it is crucial to recognize it in order to choose the best antithrombotic treatment to lower the recurrence rate. [ABSTRACT FROM AUTHOR]

Background: Communities living along the shoreline and on the islands of Lake Victoria in northwestern Tanzania remain endemic for schistosomiasis and suffer from the life-threatening morbidities associated with the disease. Nevertheless, the control measures particularly the mass drug administration do not cover the adult population. The current project on Ukerewe island aims to close this gap by involving adult community members in the control program. Here we report the baseline results of S. mansoni infection and associated hepatosplenic morbidities and factors before implementing the project activities. Methods: A cross-sectional analytical study was conducted with 4,043 participants aged ≥ 18 years living in 20 villages on Ukerewe island, northwestern Tanzania. Individual stool and urine samples were collected and examined using the Kato-Katz (KK) technique and point-of-care circulating cathodic antigen testing(POC-CCA) to identify S. mansoni eggs and antigens, respectively. All study participants underwent ultrasound evaluation of S. mansoni hepatosplenic morbidities using the Niamey protocol. Rapid diagnostic tests were used to diagnose HIV infection, hepatitis C and chronic hepatitis B. A questionnaire was used to collect demographic data and reported clinical symptoms of study participants. Results: A total of 4,043 participants took part in the study, of which 49.7% (n = 2,009) and 50.3% (n = 2,035) were male and female, respectively. The overall prevalence of S. mansoni infection was 30.4% (95%CI:29.0-31.9%) and 84.7% (95%CI:83.3–85.9%), respectively, based on the KK technique and the POC-CCA test. The geometrical mean eggs per gram of faeces (GMepg) was 105.3 (95%CI:98.7-112.3% GMepg) with 53.9%, 32.4% and 13.7% of the participants having mild, had moderate and severe intensity of infection. The prevalence of hepatitis C, HIV, and hepatitis B was 0.4%, 2.2% and 4.7%, with 0.2%, 2.2% and 5.4% of the infected individuals coexisting with S. mansoni infection. The prevalence of splenomegaly, periportal fibrosis, hepatomegaly, and portal vein dilatation was 40.5%(95%CI: 38.8–42.1%), 48.1%(95%CI:64.4–49.7%), 66.2%(95%CI:4.6–67.7%) and 67.7%(95%CI:66.2–69.2%), with their prevalence varying depending on the demographic information and infection status of the participants. Other detectable ultrasound-related morbidities included ascites (1.7%), collateral veins (18.3%) and gall bladder wall thickness (40.4%). Age groups, gender, reported clinical characteristics, reported non-use of the drug praziquantel, liver imaging pattern, and place of residence remained independently associated with hepatosplenic morbidities. Conclusion: The current study setting is endemic for S. mansoni infection and the population has a high prevalence of the disease associated hepatosplenic morbidities characterized by hepatomegaly, splenomegaly, ascites, gall bladder wall thickening, periportal fibrosis and portal vein dilatation. Several demographic, clinical and epidemiological circumstances remained independently associated with S. mansoni infection and associated morbidities. These findings call for integrative intervention efforts, starting with whole community MDA that includes all out of schools community members. [ABSTRACT FROM AUTHOR]

Abstract Background Hereditary spherocytosis is a rare genetic disorder of the red blood cell membrane that is characterized by anemia, jaundice, and splenomegaly; however, in the absence of family history and with unusual clinical presentation, the diagnosis might not be made until later in life. Case presentation Here, we present a challenging case of genetically proven hereditary spherocytosis that involves the SPTB gene in a 23-year-old female patient from Ethiopia who had repeated medical visits for episodic jaundice and hepatosplenomegaly, with unusual features of conjugated hyperbilirubinemia, pancytopenia, normal reticulocyte count, and lack of family history, where the delay in diagnosis led to several complications. The patient was successfully managed with simultaneous splenectomy and cholecystectomy. Conclusion This case underscores the importance of a thorough clinical examination, spending the time to review a case periodically without assuming the initial diagnosis is correct, and maintaining a healthy skepticism of inconsistent data to prevent misdiagnosis and mistreatment. The diagnostic delay highlights the need for increased awareness and familiarity with diagnostic modalities of hereditary spherocytosis among healthcare providers in Ethiopia.

Abstract Background Communities living along the shoreline and on the islands of Lake Victoria in northwestern Tanzania remain endemic for schistosomiasis and suffer from the life-threatening morbidities associated with the disease. Nevertheless, the control measures particularly the mass drug administration do not cover the adult population. The current project on Ukerewe island aims to close this gap by involving adult community members in the control program. Here we report the baseline results of S. mansoni infection and associated hepatosplenic morbidities and factors before implementing the project activities. Methods A cross-sectional analytical study was conducted with 4,043 participants aged ≥ 18 years living in 20 villages on Ukerewe island, northwestern Tanzania. Individual stool and urine samples were collected and examined using the Kato-Katz (KK) technique and point-of-care circulating cathodic antigen testing(POC-CCA) to identify S. mansoni eggs and antigens, respectively. All study participants underwent ultrasound evaluation of S. mansoni hepatosplenic morbidities using the Niamey protocol. Rapid diagnostic tests were used to diagnose HIV infection, hepatitis C and chronic hepatitis B. A questionnaire was used to collect demographic data and reported clinical symptoms of study participants. Results A total of 4,043 participants took part in the study, of which 49.7% (n = 2,009) and 50.3% (n = 2,035) were male and female, respectively. The overall prevalence of S. mansoni infection was 30.4% (95%CI:29.0-31.9%) and 84.7% (95%CI:83.3–85.9%), respectively, based on the KK technique and the POC-CCA test. The geometrical mean eggs per gram of faeces (GMepg) was 105.3 (95%CI:98.7-112.3% GMepg) with 53.9%, 32.4% and 13.7% of the participants having mild, had moderate and severe intensity of infection. The prevalence of hepatitis C, HIV, and hepatitis B was 0.4%, 2.2% and 4.7%, with 0.2%, 2.2% and 5.4% of the infected individuals coexisting with S. mansoni infection. The prevalence of splenomegaly, periportal fibrosis, hepatomegaly, and portal vein dilatation was 40.5%(95%CI: 38.8–42.1%), 48.1%(95%CI:64.4–49.7%), 66.2%(95%CI:4.6–67.7%) and 67.7%(95%CI:66.2–69.2%), with their prevalence varying depending on the demographic information and infection status of the participants. Other detectable ultrasound-related morbidities included ascites (1.7%), collateral veins (18.3%) and gall bladder wall thickness (40.4%). Age groups, gender, reported clinical characteristics, reported non-use of the drug praziquantel, liver imaging pattern, and place of residence remained independently associated with hepatosplenic morbidities. Conclusion The current study setting is endemic for S. mansoni infection and the population has a high prevalence of the disease associated hepatosplenic morbidities characterized by hepatomegaly, splenomegaly, ascites, gall bladder wall thickening, periportal fibrosis and portal vein dilatation. Several demographic, clinical and epidemiological circumstances remained independently associated with S. mansoni infection and associated morbidities. These findings call for integrative intervention efforts, starting with whole community MDA that includes all out of schools community members.

Background. Niemann-Pick disease, type A is a rare hereditary disease from the group of lysosomal storage diseases, it is characterized by early onset and progressive course. Description of this disease’s clinical cases is crucial for early diagnosis and adequate management due to its rarity, rapid progression, and the development of new pathogenetic therapy methods.Clinical case description. The disease manifested on the second month of the patient’s life with poor weight gain, frequent pneumonia, hepatosplenomegaly, diffuse muscular hypotonia, delayed motor development, and progressive neurological symptoms. Laboratory testing has revealed significant decrease in sphingomyelinase activity in blood. The heterozygous deletion c.996del in exon 2 of the SMPD1 gene has been revealed via direct automatic sequencing; it leads to frameshifting p.F333Sfs*52 (inherited from mother). Moreover, the previously described pathogenic nucleotide variant c.1252C>T (heterozygous) has been revealed in exon 3 of the SMPD1 gene; it leads to translation arrest p.Arg418* (inherited from father). Cherry-red spots were diagnosed at fundospcopy. The diagnosis of Niemann-Pick disease, type А was established according to clinical signs and molecular genetic testing results.Conclusion. The detection of physical and motor development delay, diffuse muscular hypotonia, hepatosplenomegaly, cherry-red spots at ophthalmological examination, lung involvement, recurrent pneumonia, and progressive neurological symptoms in a child during the first months of life indicates that this patient has Niemann-Pick disease, type А. Early molecular genetic testing is crucial for timely choosing the management approach and further genetic counselling of the family.

Rationale: Lepromatous leprosy can have many atypical presentations, obscuring early diagnosis. We present a case of lepromatous leprosy, presenting with atypical features, which made a diagnostic dilemma. Patient concerns: A 48-year-old man presented with bilateral lower limb oedema and scaly “ichthyosis like” skin rash in both hands and feet, hepatosplenomegaly and pancytopenia, over a course of three months, without any classical features of leprosy. A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy. Diagnosis: Lepromatous leprosy. Interventions: Multi-drug regimen treatment with rifampicin, dapsone and clofazimine for lepromatous leprosy. Outcomes: The patient made a good clinical recovery. Lessons: In endemic settings, clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease.

Adrianus Surya Wira Rajasa,1 Wahyu Hidayat2 1Oral Medicine Residency Program, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia; 2Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, Bandung, IndonesiaCorrespondence: Adrianus Surya Wira Rajasa, Padjadjaran University, Jl. Sekeloa Selatan No. 1, Bandung, West Java, 40132, Indonesia, Tel +62222533044, Email adrianus21001@mail.unpad.ac.idBackground: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unknown etiology resulting in chronic multi-organ inflammation. Juvenile Systemic Lupus Erythematosus (JSLE) is a specific diagnosis of SLE in juvenile, characterized by oral ulceration.Purpose: This case report attempts to provide information for oral medicine specialists in managing JSLE patients with hepatosplenomegaly.Case Presentation: A 17-year-old female patient was referred from the Pediatrics Department with mouth ulcers accompanied by dry lips and a tendency to bleed. The most concerning lesion was located on the left buccal mucosa, a single ulceration measuring 5x6mm. Multiple ulcerations spread over the upper and lower labial mucosa, with haemorrhagic crusts on the lips. Painful ulceration can lead to difficulties in mouth opening and impaired function in eating and drinking. Central erythema was seen on the palate. Pseudomembranous candidiasis was also seen on the patient’s tongue. The hepatosplenomegaly was confirmed by CT scan, with enzyme values of SGPT (386 U/L) and SGOT (504 U/L).Case Management: Administration of 0.9% NaCl was instructed to the patient to maintain oral hygiene and help moisturize lips in order to remove haemorrhagic crusts. Administration of 0.025% hyaluronic acid mouthwash and topical steroid ointment mixture for ulcerated and inflammatory conditions. Drug adjustments were made based on laboratory tests and the patient’s clinical condition was improving.Conclusion: Managing oral symptoms helps reduce morbidity in JSLE patients. Topical corticosteroids are considered the first line in controlling oral inflammation. Dentists play a role in improving patients’ oral hygiene with the aim of reducing the risk of other opportunistic infections.Keywords: hepatosplenomegaly, juvenile SLE, SLE, oral ulcer

Non-resolving consolidation refers to the persistence of radiographic abnormalities beyond the anticipated timeframe. Conditions such as infection, malignancy, inflammatory disorders, and connective tissue diseases can all manifest as non-resolving consolidation. We share a clinicopathological case study involving a 30-year-old male who exhibits nonresolving consolidation accompanied by hepatosplenomegaly. [ABSTRACT FROM AUTHOR]

ABSTRACT Seronegative antiphospholipid syndrome (SN‐APS) is uncommon and challenging condition, which should be included in the differential diagnosis of stroke in young, since it can result in arterial thrombosis.SN‐APS is typically diagnosed by exclusion; however, it is crucial to recognize it in order to choose the best antithrombotic treatment to lower the recurrence rate.

Non-resolving consolidation refers to the persistence of radiographic abnormalities beyond the anticipated timeframe. Conditions such as infection, malignancy, inflammatory disorders, and connective tissue diseases can all manifest as non-resolving consolidation. We share a clinicopathological case study involving a 30-year-old male who exhibits non-resolving consolidation accompanied by hepatosplenomegaly.

Chiari I Malformation and Intramedullary Hemorrhage in a Female Patient with Klippel Trenaunay Syndrome: A Rare Case Report Study

Background/Objectives: Gaucher disease type 1 (GD1) is characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations requiring regular MRI monitoring. The EIROS study assessed the real-world impact of velaglucerase alfa on GD1 bone disease, using MRI data collected in French clinical practice. Methods: MRIs collected retrospectively from treatment initiation and prospectively during follow-up (12-months) were analyzed centrally by a blinded expert radiologist to evaluate bone infiltration using the Bone Marrow Burden (BMB) score and a qualitative method (stable, improved or worsened for the spine and femur). Abdominal MRIs were also centrally analyzed to assess hepatosplenomegaly. Bone manifestations, hepatosplenomegaly, and hematologic parameters were analyzed from medical records. Results: MRI data were available for 20 patients: 6 treatment-naive patients and 14 patients who switched to velaglucerase alfa from another GD treatment. Interpretable MRIs for BMB scoring were available for seven patients for the spine and one patient for the femur. Qualitative assessments (n = 18) revealed stability in spine and femur infiltration in 100.0% and 84.6% of treatment-switched patients (n = 13), respectively, and improvements in 80.0% and 60.0% of treatment-naive patients (n = 5), respectively; no worsening of bone infiltration was observed. Liver, spleen, and hematologic parameters improved in treatment-naive patients and remained stable in treatment-switched patients. Conclusions: The qualitative real-world data support findings from clinical trials suggesting the long-term effectiveness of velaglucerase alfa on GD1 bone manifestations. When MRI assessment by radiologists with experience of GD is not possible, a simplified qualitative assessment may be sufficient in clinical practice for monitoring bone disease progression and treatment response. [ABSTRACT FROM AUTHOR]

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The megakaryocyte and platelet inhibitory receptor gene G6P (MPIG6B) is located on chromosome 6p21.33. It encodes G6b-B; an inhibitory receptor expressed on the surface of platelets. It regulates platelets production, aggregation, and activation. We describe a case of a 31-year-old man who presented with a long history of thrombocytopenia, anemia, and hepatosplenomegaly. The patient received multiple blood transfusions and his clinical course was stable. A bone marrow biopsy showed morphologic features similar to primary myelofibrosis. Whole exome sequencing study was performed and revealed homozygous pathogenic mutation in exon 2 of MPIG6B gene (c.324C > A, p.Cys108Ter) that is the second reported case in literature. In this report, we describe the main clinical and pathologic features of this disease and review the literature of previously documented cases.

Background: Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic metabolite buildup. It manifests in acute, subacute, and chronic forms, with early diagnosis and Nitisinone treatment being vital. Objectives: The study aims to highlight the different clinical presentations of Hereditary Tyrosinemia type 1 in a cohort of Pakistani children. Design: Retrospective observational study. Methodology: All patients diagnosed with HT1 at Shifa International Hospital, Islamabad and Pak Emirates Military Hospital, Rawalpindi between 2010 and 2023 were included. Information was collected regarding age, gender, symptoms, physical signs, and laboratory results. Results: The study identified 6 cases of HT1. The average age at presentation was 8 months, with a mean delay in diagnosis of 26.8 months. Males were 4 (66.7%) and 2 (33.3%) were females. All patients had underlying liver disease presenting as abdominal distension with hepatosplenomegaly and accompanying growth failure. Four cases presented with rickets, 2 of which had hypophosphatemic rickets. Urine for succinylacetone was raised in all patients. Alpha fetoprotein was raised but hepatocellular carcinoma was diagnosed in 1 patient only. Low protein diet, and vitamin supplements were used for management. Five of the 6 patients died within 2 years of diagnosis. Conclusion: Delayed referrals and unavailability of Nitisinone are the major challenges in diagnosing and treating HT1 in Pakistan. [ABSTRACT FROM AUTHOR]

Clinical findings of hepatomegaly and splenomegaly, the abnormal enlargement of the liver and spleen, respectively, should prompt a broad differential diagnosis that includes metabolic, congestive, neoplastic, infectious, toxic, and inflammatory conditions. Among the metabolic diseases, lysosomal storage diseases (LSDs) are a group of rare and ultrarare conditions with a collective incidence of 1 in 5000 live births. LSDs are caused by genetic variants affecting the lysosomal enzymes, transporters, or integral membrane proteins. As a result, abnormal metabolites accumulate in the organelle, leading to dysfunction. Therapeutic advances, including early diagnosis and disease-targeted management, have improved the life expectancy and quality of life of people affected by certain LSDs. To access these new interventions, LSDs must be considered in patients presenting with hepatomegaly and splenomegaly throughout the lifespan. This review article navigates the diagnostic approach for individuals with hepatosplenomegaly particularly focusing on LSDs. We provide hints in the history, physical exam, laboratories, and imaging that may identify LSDs. Additionally, we discuss molecular testing, arguably the preferred confirmatory test (over biopsy), accompanied by enzymatic testing when feasible. [ABSTRACT FROM AUTHOR]

Klippel Trenaunay Syndrome (KTS) is a rare vascular disorder characterized by a triad of symptoms including capillary malformations known as port-wine stains, venous varicosities, and osseous- or soft-tissue hypertrophy of the affected extremity. The etiology remains ambiguous, although genetic factors have been implicated. We present a case of a 27-year-old female with KTS who presented with progressive right sided paresis. An intramedullary hemorrhage and syringomyelia of the cervical spine, along with a Chiari I malformation were identified in brain and cervical spine MRI. Her laboratory tests revealed significant coagulopathy. Our patient was initially treated conservatively before she discharged for both a scheduled neurosurgical procedure and splenectomy. [ABSTRACT FROM AUTHOR]

We report a 7-month-old Thai girl diagnosed with a Niemann-Pick Disease (NPD) Type A. Hepatosplenomegaly was initially noticed at the age of 2 months. She developed progressive neurodevelopmental delay at 5 months. Other typical manifestations include coarse facies, cherry red spot of macula, hypotonia, and failure to thrive. A liver biopsy demonstrated an accumulation of enlarged histiocytes with foamy appearance in hepatic sinusoids. An acid sphingomyelinase activity from dried blood spot showed low activity. A novel c.1241T>C variant in SMPD1 was identified. The patient died at 4 years of age due to neurological decline and respiratory failure. Even in type A, onset of systemic symptoms occurs before neurodevelopmental delay. NPD type A is exceptionally rare in Thailand. Infantile neurovisceral ASMD prognosis is poor, often fatal by age 3. No specific NPD type A treatment exists; supportive care is offered. Therefore, the case reveals a novel SMPD1 variant in typical NPD type A symptoms. Early progressive neurodevelopmental delay challenges treatment study.

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematologic disorder resulting from an ineffective and pathologic activation of the immune response system that may mimic common emergency department presentations, including sepsis, acute liver failure, disseminated intravascular coagulation, and flu-like illnesses such as coronavirus disease 2019 (COVID-19).ObjectiveThis narrative review provides a summary of the disease and recommendations for the recognition and diagnostic evaluation of HLH with a focus on the emergency clinician.DiscussionThough the condition is rare, mortality rates are high, ranging from 20% to 80% and increasing with delays in treatment. Importantly, HLH has been recognized as a severe variation of the cytokine storm associated with COVID-19. Common features include a history of infection or malignancy, fever, splenomegaly or hepatomegaly, hyperferritinemia, cytopenias, coagulopathies, abnormal liver enzymes, and hypertriglyceridemia. Using specific features of the history, physical examination, laboratory studies, and tools such as the HScore, HLH-2004/2009, and hyperferritinemia thresholds, the emergency clinician can risk-stratify patients and admit for definitive testing. Once diagnosed, disease specific treatment can be initiated.ConclusionThis review describes the relevant pathophysiology, common presentation findings, and a framework for risk stratification in the emergency department.

Background:. Hemophagocytic lymphohistosis (HLH) is a life-threatening clinical syndrome that involves liver dysfunction and can range from mild dysfunction to severe fulminant insufficiency. Cholestasis, which is a frequent finding in many severe newborn illnesses, may also be a symptom of HLH. Therefore, HLH should be considered in the differential diagnosis of all cholestatic patients with cytopenia. In this report, we identified a case of HLH with cholestasis. The patient met at least seven out of the eight requirements of the HLH-2004 criteria. The infant had a stable fever, jaundice (conjugated hyperbilirubinemia), cytopenia, elevated liver enzymes, high ferritin, low fibrinogen, and triglyceride. Although urine, blood, and cerebrospinal fluid (CSF) culture tests were negative, CSF analysis revealed 80 WBCs, including 68% polymorphonuclear neutrophils (PMNs), more than 100000 RBCs, 71 mg/dL sugar, 82 mg/dL protein and 102 U/L lactate dehydrogenase. Coagulation tests and TORCH screen were normal. We confirmed the diagnosis of HLH with a bone marrow aspiration test and started treatment with dexamethasone. An intravenous dose of dexamethasone (4 mg) was administered, followed by 1.5 mg daily with pressure control, which stopped the fever after 24 hours. Case report: The patient was a 21-day-old infant with a birth weight of 3450 g. He developed fever and jaundice 10 days after a normal delivery, and he was referred to Sarakhs Hospital when he was 14 days old and hospitalized for 3 days. Later, he was sent to Ghaem Hospital and admitted to the Neonatal Intensive Care Unit. The infant had a stable fever, jaundice (conjugated hyperbilirubinemia), cytopenia, elevated liver enzymes, high ferritin, low fibrinogen, and triglyceride. According to his mother, there was no history of any problems from birth, and the baby's jaundice started after the first week. Examinations showed abdominal distention and hepatosplenomegaly. Due to neonatal cholestasis and fever, he underwent a complete sepsis workup with vancomycin and cefotaxime. Although urine, blood, and cerebrospinal fluid (CSF) culture tests were negative, CSF analysis revealed 80 WBCs, including 68% polymorphonuclear neutrophils, more than 100000 RBCs, 71 mg/dL sugar, 82 mg/dL protein, and 102 U/L lactate dehydrogenase. Coagulation tests and TORCH screen were normal. We confirmed the diagnosis of hemophagocytic lymphohistiocytosis (HLH) with a bone marrow aspiration test and started treatment with dexamethasone. An intravenous dose of dexamethasone (4 mg) was administered, followed by 1.5 mg daily with pressure control, which stopped the fever after 24 hours. Conclusion:HLH is uncommon in the neonatal stage, and aberrant clinical and laboratory findings suggestive of HLH can be found in a variety of conditions. The severity of this condition makes it crucial to get a diagnosis as soon as possible. In the presence of additional variables, such as cytopenia and hyperferritinemia, HLH should be considered in the differential diagnosis of cholestasis in a neonate.

Disseminated Peritoneal Leiomyomatosis (DPL) is characterised by multiple smooth muscle tissues over the peritoneal surface of the pelvic and abdominal cavity. Possible causes of DPL include hormonal factors, subperitoneal mesenchymal stem cell metaplasia, genetic factors, or iatrogenic factors. Hereby, the authors represents a case of DPL in a 42-year-old female with a history of two Laparoscopic Myomectomies. She presented with complaints of abdominal distension and bilateral lower limb pain lasting eight months. She underwent a robotic hysterectomy with bilateral salpingectomy and the removal of intraperitoneal nodules. Intraoperative findings showed a mass resembling leiomyoma over the uterus, mesentery, spleen, and rectosigmoid. She was discharged on postoperative day 4 and has been asymptomatic for the past two years. Robotic surgery is an emerging surgical modality in the treatment of DPL due to its better precision and ease of accessibility to upper abdominal organs. More importantly, recovery time is enhanced, and it reduces the duration of hospital stay.

Congenital syphilis (CS) is a vertically transmitted infection caused by the spirochete Treponema pallidum. It is seen rarely due to proper antenatal screening. Signs and symptoms appear within the first 2 years of life in early CS and after 2 years in late CS. Failure to diagnose and treat CS in its early stages can result in higher morbidity and mortality. Skin manifestations can guide toward the diagnosis of CS at an early stage. Here, we report a 2‑day‑old neonate who presented with acral peeling of skin along with respiratory distress and hepatosplenomegaly. Clinical suspicion of CS was made and subsequently confirmed by a positive venereal disease research laboratory test in both mother and child. The child was treated with aqueous crystalline penicillin G as per the CDC guidelines. [ABSTRACT FROM AUTHOR]

Gray platelet syndrome (GPS) is a rare hereditary hemorrhagic disorder characterized by macrothrombocytopenia and the absence of alpha-granules in platelets. Clinically, mild-to-moderate bleeding is the main manifestation, often accompanied by thrombocytopenia, splenomegaly, and myelofibrosis. Here, we present a case of a 15-year-old male patient with a history of hepatosplenomegaly, and thrombocytopenia for 8 years, who presented with sudden generalized abdominal pain. Despite initial suspicion of gastroenteritis, diagnostic imaging revealed an extensive hemoperitoneum. Subsequent genetic testing confirmed the diagnosis of GPS, which had not been previously identified. This case highlights the importance of considering inherited platelet disorders should be considered in adolescents with long-standing thrombocytopenia, and emphasizes the need for thorough evaluation in patients with suggestive symptoms. [ABSTRACT FROM AUTHOR]

Background: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinical Description: A 2-month-old baby boy presented with features of lower respiratory tract infection, along with a swollen right upper arm due to fracture of humerus, along with signs of bicytopenia and hepatosplenomegaly. He had a history of hypocalcemic seizures at 8th day of life. Management and Outcome: Current hospitalization revealed refractory hypocalcemia and hypophosphatemia with normal to increased Vitamin D and parathormone levels and increased density of bone. Hypocalcemia was particularly refractory in nature needing multiple intravenous calcium corrections. Whole exome sequencing detected compound heterozygous variants in the T-cell immune regulator 1 pathogenic gene of IMO. Simultaneously, a heterozygous nonsense variation in exon 4 of the CHRNA4 gene was detected causing nocturnal frontal lobe epilepsy. As the infant had evidence of bone marrow failure, he was considered and referred for hematopoietic stem cell transplantation. Conclusion: Neonatal and early infantile hypocalcemia are commonly seen by pediatricians, but an etiology of IMO is rarely considered. The presence of fracture of long bones with cytopenias and hepatosplenomegaly in a young infant with recurrent hypocalcemia, without Vitamin D deficiency, should raise suspicion of this disorder and genetic analysis should be carried out for the same.

Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder that presents as an isolated polycystic renal disease in childhood, or associated with congenital hepatic fibrosis and/or Caroli disease. The spectrum of complications of ARPKD include end stage kidney disease, systemic hypertension and liver disease. Anemia in ARPKD is commonly due to be reduced erythropoietin or iron deficiency. We present a 2-year old male patient with ARPKD who presented to the emergency room by striking pallor and dark urine. Initial lab work revealed Hemoglobin level 2g/dL. Blood transfusion was challenging due to difficult typing and frequent mismatch. Other labs showed elevated urea and creatinine, positive direct Coomb’s anticoagulant test and positive urine culture. Imaging was consistent with ARPKD. The patient was resuscitated and after stabilization, he received pulsed methylprednisolone at 30 mg/day for 5 days followed by prednisone 2mg/kg/day for 4 weeks that was tapered over 2 months with marked improvement. Herein we report autoimmune hemolytic anemia as another and rare cause for anemia associated with ARPKD.

Abstract Background The differential diagnosis of multiple unexplained bone fractures in a young infant usually includes child abuse or bone disease such as osteogenesis imperfecta. Bone abnormalities can occur in 60–80% of cases with congenital syphilis and may be the sole manifestation. However, this frequent manifestation of this rare disease such as congenital syphilis is frequently disregarded. We describe a case of a young infant with multiple long bone fractures diagnosed with congenital syphilis. Case presentation This 2-month-old male patient was referred to our hospital because of fractures of the ulna and distal radius bilaterally and noisy breathing with the suspicion of osteogenesis imperfecta. After thorough examination, the infant had anemia and a palpable spleen. We performed a screen for congenital infections among other investigations, which revealed positive non-treponemal and treponemal antibodies for syphilis. Hence the diagnosis for Congenital Syphilis was made. We performed a lumbar puncture (LP) which showed mild pleocytosis. The patient was treated with intravenous aqueous penicillin G 200 000 UI/KG per day for 10 days. In addition, a single dose of intramuscular penicillin G benzathine 50 000 UI/KG was given due to the abnormal result of CSF. On follow up admission 6 months later, the new syphilis serology had much improved and the new LP revealed no abnormal findings. Conclusions We present this case report in order to remind of a common manifestation of congenital syphilis, a rare disease which needs to be included in the differential diagnosis of multiple unexplained fractures in early infancy. In our case the fractures were symmetric and bilateral and they were accompanied by anemia and mild hepatosplenomegaly which led to the investigation of congenital syphilis as a possible cause. However, two thirds of infants with congenital syphilis are asymptomatic at birth. All women should have a proper syphilis screening during pregnancy.

Background:. Hemophagocytic lymphohistosis (HLH) is a life-threatening clinical syndrome that involves liver dysfunction and can range from mild dysfunction to severe fulminant insufficiency. Cholestasis, which is a frequent finding in many severe newborn illnesses, may also be a symptom of HLH. Therefore, HLH should be considered in the differential diagnosis of all cholestatic patients with cytopenia. In this report, we identified a case of HLH with cholestasis. The patient met at least seven out of the eight requirements of the HLH-2004 criteria. The infant had a stable fever, jaundice (conjugated hyperbilirubinemia), cytopenia, elevated liver enzymes, high ferritin, low fibrinogen, and triglyceride. Although urine, blood, and cerebrospinal fluid (CSF) culture tests were negative, CSF analysis revealed 80 WBCs, including 68% polymorphonuclear neutrophils (PMNs), more than 100000 RBCs, 71 mg/dL sugar, 82 mg/dL protein and 102 U/L lactate dehydrogenase. Coagulation tests and TORCH screen were normal. We confirmed the diagnosis of HLH with a bone marrow aspiration test and started treatment with dexamethasone. An intravenous dose of dexamethasone (4 mg) was administered, followed by 1.5 mg daily with pressure control, which stopped the fever after 24 hours. Case report: The patient was a 21-day-old infant with a birth weight of 3450 g. He developed fever and jaundice 10 days after a normal delivery, and he was referred to Sarakhs Hospital when he was 14 days old and hospitalized for 3 days. Later, he was sent to Ghaem Hospital and admitted to the Neonatal Intensive Care Unit. The infant had a stable fever, jaundice (conjugated hyperbilirubinemia), cytopenia, elevated liver enzymes, high ferritin, low fibrinogen, and triglyceride. According to his mother, there was no history of any problems from birth, and the baby's jaundice started after the first week. Examinations showed abdominal distention and hepatosplenomegaly. Due to neonatal cholestasis and fever, he underwent a complete sepsis workup with vancomycin and cefotaxime. Although urine, blood, and cerebrospinal fluid (CSF) culture tests were negative, CSF analysis revealed 80 WBCs, including 68% polymorphonuclear neutrophils, more than 100000 RBCs, 71 mg/dL sugar, 82 mg/dL protein, and 102 U/L lactate dehydrogenase. Coagulation tests and TORCH screen were normal. We confirmed the diagnosis of hemophagocytic lymphohistiocytosis (HLH) with a bone marrow aspiration test and started treatment with dexamethasone. An intravenous dose of dexamethasone (4 mg) was administered, followed by 1.5 mg daily with pressure control, which stopped the fever after 24 hours. Conclusion:HLH is uncommon in the neonatal stage, and aberrant clinical and laboratory findings suggestive of HLH can be found in a variety of conditions. The severity of this condition makes it crucial to get a diagnosis as soon as possible. In the presence of additional variables, such as cytopenia and hyperferritinemia, HLH should be considered in the differential diagnosis of cholestasis in a neonate. [ABSTRACT FROM AUTHOR]

Introduction and importance: Gaucher's disease (GD) or lysosomal storage disease, is one of the rare genetic disorders resulting from glucocerebrosidase deficiency. Clinical manifestations include a swollen belly (hepatosplenomegaly), bruising due to thrombocytopenia, anemia, fatigue, bone pain, and neurological involvement. Diagnosis is made by measuring the level of glucocerebrosidase enzyme in the blood, using dual energy X-ray absorptiometry (DXA), and performing genetic tests. For some types of GD, enzyme therapy is now available. Case presentation: A 5-year-old child with a high-grade fever and splenomegaly was admitted to our teaching hospital's pediatric surgery department. The patient had genetic screening in early childhood outside the country, confirming the diagnosis of GD. Following the appropriate anti-bacterial therapy, the patient underwent splenectomy for conditions such as splenomegaly, lack of enzyme replacement therapy, and the patient's susceptibility to trauma. Clinical discussion: GD is a rare disease that is frequently confused with thalassemia. If there are no visible signs and symptoms, the disease is overlooked and left untreated. Our clinical justifications for surgical operation (splenectomy) were splenomegaly, lack of enzyme replacement therapy (an integral part of gaucher's disease treatment), and prevention of splenic rupture (as a result of falling down due to child neglect, which is common in Afghanistan). During the 1-year post-operative follow-up, our patient experienced two episodes of high-grade fever, which were treated appropriately. Conclusion: Due to the rarity of GD, the disease is left untreated and undiagnosed for a long time, mainly in developing countries where definite diagnostic modalities are not readily available. Diseases with similar symptoms should always be considered in the differential diagnosis. Early enzyme replacement therapy is the key to improve the quality of life, but it is not available in developing nations.

BackgroundBlau syndrome (BS) is a monogenic disorder caused by NOD2 gene variants characterized by the triad of granulomatous polyarthritis, rash, and uveitis. Atypical symptoms were recognized in one-third to one-half of individuals with BS. This study aims to describe the clinical features of BS patients with hypertension and digestive system involvement.MethodsThe complete clinical data of a BS patient complicated with hypertension and hepatic granulomas were collected and documented. We also performed a literature search to find all reported cases of BS with hypertension and digestive system involvement.ResultsWe reported the case of a 19-year-old man who presented with early onset symmetric polyarthritis and hypertension at age 5 and hepatic granulomas and cirrhosis at age 19. He was diagnosed with BS by the finding of a variant of the NOD2 gene (R334W). Through the literature review, 24 patients with BS were found who were reported to have hypertension, and 38 patients were found who had different digestive system manifestations such as hepatic granulomas, hepatosplenomegaly, diverticulitis, and intestinal granuloma. Among the 38 BS patients with digestive system involvement, 14 had hepatic granulomas proven by liver biopsy.ConclusionsHypertension and digestive system involvement are rare manifestations of BS. Clinicians, especially rheumatologists, must be aware of atypical symptoms of BS.

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient’s clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia.

Human Parvovirus B19 causes mild to life-threatening illnesses, especially in immunosuppressed individuals. In the immunocompetent individuals, the severe spectrum of clinical manifestations of the virus infection is not widely known. This case series presents the spectrum of clinical manifestations of serious Parvovirus B19 infection in children without any chronic haematological or immunodeficiency disease. This series is about a total of 12 children who were positive for Parvovirus Immunoglobulin M (IgM) antibody and the age range was between 1-12 years. Fever, fatigue, and arthritis were the most common manifestations. Pure red cell aplasia, the specific manifestation of Parvovirus infection, was seen only in one-third of patients. All the children were treated with Intravenous Immunoglobulin (IVIG) along with supportive therapy. All except one had a successful recovery.

Sarcoidosis is rare multi-system granulomatous inflammatory disorder. It is reported to present by two distinct presentations in childhood. Sarcoidosis presents in the second decade of life by pulmonary infiltration, lymphadenopathy and hepatosplenomegaly, and rarely before the age of 4 years by typical triad of uveitis, rash and arthritis. We report a child 1 year and 9 months with sarcoidosis who presented by one month fever, hepatosplenomegaly, uveitis, pulmonary infiltration and elevated levels of angiotensin-converting enzyme. Chest computerized tomography revealed multiple enlarged mediastinal and multiple hilar lymphadenopathy. A right inguinal lymph node biopsy showed non-caseating granuloma. Other etiologies were investigated for and ruled out. Hence, sarcoidosis can present in children before 4 years with uveitis, hepatosplenomegaly, pulmonary infiltrates, mediastinal and hilar lymphadenopathy, in the absence of rash and arthritis. Sarcoidosis in children is rare and clinical spectrum can vary considerably. Diagnosis of sarcoidosis should be suspected in any child with uveitis.

Dear Editor, Brucellosis is multi-systemic infection with varied clinical presentation. Hematological manifestation of brucella includes, anaemia, thrombocytopenia, and pancytopenia with hepatosplenomegaly, lymphadenopathy which can be misdiagnosed as leukaemia. A 65-year-old male patient, who has been complaining for a month of fever, nocturnal sweats, widespread weakness, and abdominal pain. The patient was known to have hypertension and was on tablet Amlodipine 5 mg once day for past three years. The family history was not significant. A clinical examination revealed hepatosplenomegaly and anaemia (Hb 8.7 g/dL) (organs palpable 4 cm and 5 cm below the costal margins respectively) Leucopenia (1×109/L) was detected in the laboratory tests (neutrophils 33%, lymphocytes 60%, monocytes 5%, eosinophils and basophils 0%). Human Immunodeficiency Virus (HIV) and hepatitis B and C were ruled out by serological assays (HIV). The Antinuclear Antibody (ANA), anti-double stranded Deoxyribonucleic Acid (antidsDNA), direct and indirect Coombs tests returned negative results. Epstein-Barr virus and Cytomegalovirus (CMV) serological tests came out negative. The serological test for enteric fever came back negative, A bone marrow aspiration was done because of his ongoing cytopenia and fever, and the results revealed trilineage hyperplasia with the left shift. Due to the persistent clinical symptoms (mainly fever), the patient was interviewed again and then his profession was revealed to be a sheep herder. Thus, a provisional diagnosis of brucellosis was considered. The serological test for brucellosis sent. Brucella abortus and Brucella melitensis both had titers of >1:640 and C- reactive protein was >6 mg/mL. The blood cultures showed Gram-negative cocci growth and after fifteen days confirmed the abortus, melitensis. Thus, a diagnosis of brucella infection was finalized. The World Health Organization suggests a six-week course of doxycycline and rifampin medication for six weeks, as in present case, patient had treatment with Doxycycline 100 mg BD and Rifampicin 600 mg OD [1]. The patient was admitted for one week in our ward, and his hemogram showed improvement with treatment. After one month of treatment, his counts became normal, showing White Blood Cells (WBC) 6.5×109/L, hemoglobin (Hb) 12.5 g/dL, Mean Corpuscular Volume (MCV) 90 fl, platelets 213×109/l, and the size of his spleen and liver shrank. The fever went away, and his follow-up was still positive. The most prevalent zoonotic disease worldwide is human brucellosis. The Gram-negative coccobacillus Brucella is the culprit. In the Middle East, sub-Saharan Africa, India, and Central and South America, brucellosis is a major cause of morbidity and mortality [2,3]. Humans in endemic nations are typically exposed to the disease through eating tainted meats and unpasteurized dairy products. It primarily presents as an occupational danger in wealthy nations. Night sweats, myalgia, malaise, protracted, undulating fevers, and hepatosplenomegaly are all symptoms of brucellosis [4,5]. It primarily affects the reticuloendothelial system more than other tissues. The infection also affects other organ, heart, central nervous system, kidneys, genitourinary, cardiovascular, gastrointestinal, and cardiovascular system. In one of Turkish study of 484 cases of brucellosis, anaemia, thrombocytopenia, and leucopenia seen in 21.5%, 18.8%, 14.5% respectively. Pancytopenia observed in 2-14% patients. Lymphadenopathies are found in 10%-20% patients of brucellosis, and cervical lymph node is commonly affected [4,5]. There are no disease specific findings to differentiate between brucellosis induced cytopenia from non-infectious causes, and therefore, brucellosis infection misdiagnosed as leukaemia, lymphoma [5,6]. All these cytopenia and lymphadenopathy due to brucellosis infection responds very well to treatment. In an endemic location, a thorough patient history aids in the early identification and treatment of the patient. When a patient exhibits hepatosplenomegaly, pancytopenia, and fever, it is important to consider the differential diagnosis of brucellosis.

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well.

Background: The differential diagnosis of multiple unexplained bone fractures in a young infant usually includes child abuse or bone disease such as osteogenesis imperfecta. Bone abnormalities can occur in 60–80% of cases with congenital syphilis and may be the sole manifestation. However, this frequent manifestation of this rare disease such as congenital syphilis is frequently disregarded. We describe a case of a young infant with multiple long bone fractures diagnosed with congenital syphilis. Case presentation: This 2-month-old male patient was referred to our hospital because of fractures of the ulna and distal radius bilaterally and noisy breathing with the suspicion of osteogenesis imperfecta. After thorough examination, the infant had anemia and a palpable spleen. We performed a screen for congenital infections among other investigations, which revealed positive non-treponemal and treponemal antibodies for syphilis. Hence the diagnosis for Congenital Syphilis was made. We performed a lumbar puncture (LP) which showed mild pleocytosis. The patient was treated with intravenous aqueous penicillin G 200 000 UI/KG per day for 10 days. In addition, a single dose of intramuscular penicillin G benzathine 50 000 UI/KG was given due to the abnormal result of CSF. On follow up admission 6 months later, the new syphilis serology had much improved and the new LP revealed no abnormal findings. Conclusions: We present this case report in order to remind of a common manifestation of congenital syphilis, a rare disease which needs to be included in the differential diagnosis of multiple unexplained fractures in early infancy. In our case the fractures were symmetric and bilateral and they were accompanied by anemia and mild hepatosplenomegaly which led to the investigation of congenital syphilis as a possible cause. However, two thirds of infants with congenital syphilis are asymptomatic at birth. All women should have a proper syphilis screening during pregnancy. [ABSTRACT FROM AUTHOR]

Here we provide clinical evaluation of lymphadenopathy guided by the probability of the underlying disease to assist clinicians in establishing the proper cause and hence provide appropriate management. Both the case histories provided a common history of prolonged fever with generalized lymphadenopathy. Case 1 of adult man had additional feature of hepatosplenomegaly with pancytopenia and involvement of generalised lymphadenopathy. The order of differentials kept were disseminated tuberculosis, lymphoreticular malignancy, autoimmune disease, and metastatic malignant tumor. Case 2 of young man had additional feature of ascites without anasarca. The order of differentials kept were peritonitis (bacterial, tubercular, malignant, spontaneous), liver cirrhosis, lymphoreticular malignancy, disseminated tuberculosis, intraabdominal malignancy, others like Budd Chiari syndrome, portal vein thrombosis, pancreatic ascites at the end. The systemic approach guided us to the final diagnosis of Hodgkin lymphoma in the 1st case and non-Hodgkin lymphoma in 2nd case. Case of fever with lymphadenopathy is approached methodologically and disclosed with accurate diagnosis with minimal discomfort to the patient in a short time. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare clonal plasma cell disease associated with multisystem involvement. We reported a case of 48‐year‐old woman with large volume of exudative ascites with an increased level of λ‐light chain and hepatosplenomegaly. The patient was treated with thalidomide and dexamethasone and showed a good clinical response. [ABSTRACT FROM AUTHOR]

Abstract POEMS syndrome is a rare clonal plasma cell disease associated with multisystem involvement. We reported a case of 48‐year‐old woman with large volume of exudative ascites with an increased level of λ‐light chain and hepatosplenomegaly. The patient was treated with thalidomide and dexamethasone and showed a good clinical response.

Infantile malignant osteopetrosis (IMOP) is a rare bone resorptive disorder with an autosomal recessive inheritance pattern. It is characterized by increased bone density due to osteoclastic failure in differentiation or function. The clinical manifestations of IMOP start at birth or infancy with varied rings according to the type and degree of osteopetrosis. We presented a 3-year-old female patient referred to us due to chronic anaemia six months ago. The physical examination revealed hepatosplenomegaly, axial hypotonia, and visual impairment. Blood investigation revealed pancytopenia and hypocalcemia. Radiologic studies revealed a generalized increase in bone density, abnormal metaphyseal remodelling, and rain atrophy. The bone marrow aspiration (BMA) shows dry tap and hypocellularity of all cell lines. IMOP was diagnosed depending on clinical, radiologic, and BMA results. In conclusion, IMOP is relatively uncommon. Accurate diagnosis should be made through clinical, BMA, and radiologic investigations, especially in a resource-limited setting, as performed in our case. [ABSTRACT FROM AUTHOR]

Abstract Background Niemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in these genes are associated with abnormal endosomal–lysosomal trafficking, resulting in the accumulation of tissue-specific lipids in lysosomes. Methods We described sixteen patients with NPC diagnosed between the age of 1 month and 30 years at two tertiary care centers in Palestine. The clinical phenotype, brain magnetic resonance imaging (MRI), and molecular genetic analysis data were reviewed. Results The diagnosis was confirmed by molecular analysis in all patients. Fourteen out of sixteen patients were homozygous for the NPC1 p.G992W variant. Among them, most were categorized as having the late-infantile neurological form of disease onset. They predominantly manifested with early-onset visceral manifestations in the form of hepatosplenomegaly and prolonged neonatal jaundice, and late-onset neuropsychiatric manifestations in the form of vertical supranuclear gaze palsy (VSGP), ataxia, cognitive impairment and seizures. Brain MRI in 6 patients was normal in 5 or consistent with cerebellar hemisphere atrophy in 1 of them. Two other mutations were identified in the NPC1 gene, of which p.V845Cfs*24 was novel. Conclusions Our results revealed phenotypic heterogeneity of NPC even within the same genotype, and add to the increasingly recognized evidence that cholestatic jaundice and hepatosplenomegaly during infancy, should alert the physician for the possibility of NPC. We reported a novel mutation in the NPC1 gene further expanding its genotype.

The aim was to study the mechanisms of immunological dysregulation of cytokine and immunoglobulin production, changes in the CD expression of T and B lymphocyte subpopulations in patients with hepatosplenomegaly of different etiology. Materials and methods. We examined 73 patients with liver cirrhosis complicated by portal hypertension, hepatosplenomegaly, and bleeding from phlebectasia. We identified three groups of patients depending on the triggering factors of cirrhosis: the first (I) group – HBV/HCV; the second (II) group – CMV/VEB; the third (III) group – hereditary enzymopathies. The study material was lymphocytes and blood serum. We used the methods of ELISA, immunofluorescence and flow cytometry. Results. An increase in the concentration of IgA and IgM was revealed against the background of normal number of CD22+ B lymphocytes with HBV/HCV (I group), high level of IgM and their producers, B lymphocytes, with CMV/VEB (II group), in group III with hereditary enzymopathies, the concentration of all immunoglobulins was normal with an increased content of B lymphocytes. Multidirectional changes in the content of cytokines were revealed: in group I the synthesis of anti-inflammatory cytokines IL-4, IL-10 and in group II – pro-inflammatory IL-1β, INF-γ, TNF-α dominated; in group III the concentration of IL-6 and vascular growth factor (VEGF) was maximally increased. The number of activated CD3+CD4+CD25+ T cells was reduced in groups I and II – by 2.3 and 2.0 times respectively, in group III – increased by 1.2 times. The number of regulatory T lymphocytes CD3+CD4+CD25+CD127neg was reduced by half in I and II groups. Expression of co-stimulatory molecules CD3+CD4+CD28+ was low in all groups and the maximum decrease was in group III. In patients with HCV/HBV, an increase in the expression of the late activation marker of lymphocytes CD3+HLA-DR+ by an average of 63 % was noted. Conclusions. The revealed immune disorders in hepatosplenomegaly of different etiology are characterized by multidirectional changes. Approaches to the treatment of these patients should be complex, taking into account the trigger factors that cause dysregulation of immune responses, which leads to further destruction, and focuses at remodeling target organs.

Various factors of infectious and toxic genesis can lead to the liver cirrhosis, often accompanied by complications such as recurrent bleeding due to portal hypertension against the background of hepatosplenomegaly. Metabolic changes and disturbances in immunoreactivity occur in the liver and spleen. To substantiate the choice of personalized treatment tactics for patients with hepatosplenomegaly, we investigated individual metabolic predictors and immunopathological processes in patients with: liver cirrhosis and hepatitis B (HBV) and/or hepatitis C (HCV) viruses (I group, n = 52); with herpes viruses CMV (cytomegalovirus) and EBV (Epstein-Barr virus) (II group, n = 48), and with splenomegaly and frequent recurrent bleeding associated with hereditary enzymopathies (III group, n = 15). We used the methods of immunoturbidimetry; enzyme immunoassay; light, fluorescence and confocal microscopy. In group I (HBV/HCV), we revealed a decrease in the C4 component; a significant increase in the phagocytic index and phagocytic number, a reduced number of active phagocytes and the digestion index; a decrease in the IL-1β content and an increase in IL-18 and IL-6. In group II (CMV/EBV), we revealed a high activity of the C3 and a low activity of the C4 component against the background of a high level of ROS in neutrophils; the antineutrophil antibodies (ANCA) formation in 85.7% of patients (71.4% –perinuclear antibodies (pANCA) to myeloperoxidase; 14.3% – cytoplasmic antibodies (CANCA) to proteinase 3). Also, in group II, an increased level of pro-inflammatory cytokines IFN-γ, IL-1β, TNF-α, IL-18 and anti-inflammatory IL-6 was detected. Changes in links of immunity in II group led to the formation of autoimmune reactions in 64.7% of patients, which was expressed in the development of a broad range of antinuclear antibodies ANA (11 specificities, including ANA to chromatin and chromatin-associated proteins, to proteins cytoskeleton, enzymes and enzyme complexes). In group III, we revealed a low absorption capacity of neutrophils, a high frequency of antineutrophil antibodies pANCA occurrence and cANCA (in 67.2% of the examined), and low concentration of TNF-α. The developed model of the stepwise change of immunological markers makes it possible to substantiate the choice of a complex targeted treatment, including antiviral and immunotropic therapy.

Histoplasma capsulatum, a thermal dimorphic fungus, is the agent of histoplasmosis. It is a common cause of endemic mycosis. We report the case of a 64-year-old female, a known case of diabetes mellitus, hypertension, beta-thalassemia trait who presented with persistent fever, decreased appetite and weight loss for a period of 1 month and found to have anaemia and hepatosplenomegaly. She was diagnosed with histoplasmosis on liver biopsy. She was started on amphotericin 'B' liposomal for 14 days. She showed marked improvement symptomatically and later put on tablet itraconazole 200 mg twice a day for 1 year and was advised for follow-up.

Niemann-pick disease is a severe disorder in sphingolipid metabolism and esterification of cholesterol which results in accumulations of sphingomyelin in different tissues. This disease is characterized with hepatosplenomegaly, fever and foam cell appearance in microscopic examination of bone marrow, liver and spleen. The case presented in this study is a four-month-old female infant with chief complaint of fever, pancytopenia, and severe abdominal distension, and anemia since 10 days before admission to our hospital. The case was the third child of the family born with cesarian section and without any significant health problems before hospitalization. Her siblings had both died in the hospital, but the cause of death is unknown. Significant laboratory findings include WBC=1500 (neutrophil 70%), RBC=2,000,000, Hb=5.5 g/dl, Plt= 30,000, CRP=3+, ESR=45, ALT=300 IU, and AST-150 IU. No other abnormal findings were observed in laboratory report. Thoracoabdominal X-ray revealed significant hepatosplenomegaly. Her parents were cousins. Soon after admission to our hospital, she received a wide spectrum antibiotic, but underwent ventilator due to sepsis. Unfortunately, our therapeutic management was not successful, and the patient died due to septicemia the next morning. After obtaining written consent of the parents, the patient underwent necropsy, which revealed lipid storage disease, Niemann-pick disease. The purpose of our study was to emphasize the importance of necropsy and follow-up until a definite diagnosis.

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well. [ABSTRACT FROM AUTHOR]

Biallelic changes in the ZNFX1 gene have been recently reported to cause severe familial immunodeficiency. Through a search of our bio/databank with information from genetic testing of >55 000 individuals, we identified nine additional patients from seven families with six novel homozygous ZNFX1 variants. Consistent with the previously described phenotype, our patients suffered from monocytosis, thrombocytopenia, hepatosplenomegaly, recurrent infections, and lymphadenopathy. The two most severely affected probands also had renal involvement and clinical presentations compatible with hemophagocytic lymphohistiocytosis. The disease was less lethal among our patients than previously reported. We identified two missense changes, two variants predicted to result in complete protein loss through nonsense‐mediated decay, and two frameshift changes that likely introduce a truncation. Our findings (i) independently confirm the role of ZNFX1 in primary genetic immunodeficiency, (ii) expand the genetic and clinical spectrum of ZNFX1‐related disease, and (iii) illustrate the utility of large, well‐curated, and continually updated genotype–phenotype databases in resolving molecular diagnoses of patients with initially negative genetic testing findings. [ABSTRACT FROM AUTHOR]

Hepatosplenic T cell lymphoma (HSTCL) is a very rare and aggressive peripheral T cell lymphoma that comprises less than 1% of Non-Hodgkin lymphomas (NHL). It is derived from cytotoxic T-cells, usually of γδ T cell receptor type, and is characterized by primary extranodal disease with typical sinusoidal infiltration of the liver, spleen and bone marrow by medium-sized lymphoid cells. HSTCL occurs more frequently in immunocompromised patients, especially in those receiving long-term immunosuppressive therapy. The differential diagnosis is varied, and the clinical course is dismal with a poor response to currently available therapies. Herein we report a case of HSTCL in a 20-year-old immunocompetent male who presented with fever, pallor, weight loss, bicytopenia, hepatomegaly, and massive splenomegaly, highlighting the diagnostic conundrum and pointers towards an accurate diagnosis. The key role for diagnosis was the combination of morphologic finding of atypical lymphoid cells in the bone marrow, typical immunophenotypic profile on flow cytometry and the pattern of involvement of the liver and the spleen, even in the absence of full-fledged diagnostic panels and tools. The report of this case is an endeavor to emphasize the high index of suspicion for timely detection of such a rare entity. [ABSTRACT FROM AUTHOR]

Abstract Background Intravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. Case presentation A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. Conclusions We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.