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Life (Basel, Switzerland) Jan 2024Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it...
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, to some extent, a process of exclusion. AOSD has life-threating complications ranging from asymptomatic to severe, such as macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with cytokine storm production and monocyte/macrophage overactivation and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. For the treatment of MAS-HLH, the Histiocyte Society currently suggests high-dose corticosteroids, with the possible addition of cyclosporine A, anti-interleukin (IL)-1, or IL-6 biological drugs; the inclusion of etoposide is recommended for the most severe conditions. In all cases, a multidisciplinary collaboration involving the resources and expertise of several specialists (e.g., rheumatologist, infectiologist, critical care medicine specialist) is advised. Herein, we provide a detailed description of the clinical case of a previously healthy young woman in which MAS developed as a dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge; the condition was finally resolved by applying the HLH-94 protocol (i.e., etoposide in combination with dexamethasone).
PubMed: 38398704
DOI: 10.3390/life14020195 -
Pathogens (Basel, Switzerland) Jan 2024Shortly after the establishment of African swine fever virus (ASFV) genotype II in 2007, cases of acute fatal infection were observed. However, after several years of...
Shortly after the establishment of African swine fever virus (ASFV) genotype II in 2007, cases of acute fatal infection were observed. However, after several years of circulation in the Eurasian region, the clinical signs of the disease changed. Currently, this disease can occur acutely, subclinically, chronically, or asymptomatically. Cases of the complete recovery of infected pigs, and the disappearance of ASFV from their tissues and secretions have been described. This form of the disease first appeared in Armenia at the end of 2011. This virus was described and identified as the Dilijan2011IMB strain. The goal of our research was to study the main features of clinical, pathological, immunological, virological, and genetic parameters involved in the development of new forms of African swine fever (ASF). Chronic ASF was characterized with low titers of the virus and a decrease in the intensity of hemadsorption. Additionally, a reduced intensity in clinical symptoms and pathoanatomical results was noted. The absolute, but not the relative number of immune cells changes; the neutropenia (in bone marrow and spleen), lymphopenia (in bone marrow), lymphocytosis (only in spleen), lymphoid cell depletion (in bone marrow), and pancytopenia (in bone marrow) observed in the chronic form of ASF were less pronounced compared to in the acute form. When comparing the late stage of chronic ASF to the acute form, the key cytological indicators in the spleen, lymph nodes, and blood were less severe in the chronic stage. Bone marrow failure in the chronic form, expressed in a pronounced decrease in all cell types, generally coincided with the data in the acute form of ASF. The same data were obtained after assessing serum TNF-alpha levels. Thus, we can conclude that the chronic form of ASF occurs due to a less pronounced immune response, as well as a decrease in virus titers in the blood and tissues of infected pigs.
PubMed: 38392868
DOI: 10.3390/pathogens13020130 -
Indian Journal of Pathology &... Apr 2024Hemophagocytic lymphohistiocytosis (HLH) is a severe and frequently underdiagnosed disorder of systemic immune dysregulation resulting in hypercytokinemia and...
Hemophagocytic lymphohistiocytosis (HLH) is a severe and frequently underdiagnosed disorder of systemic immune dysregulation resulting in hypercytokinemia and histologically evident hemophagocytosis, We report a case of a 34-year-old man who presented with breathlessness, generalized weakness, and fever of unknown origin with pancytopenia. Clinically the patient was admitted for febrile illness, and treated symptomatically but his general condition worsened leading to death within 21 hours of admission. A complete autopsy was performed. The deceased had a significant past history of repeated episodes of fever, weight loss, and axillary lymphadenopathy over a period of 8 months with multiple hospital admissions. He was also diagnosed with enteric fever (Widal test and Typhi IgM positive) at the start of these episodes. Hemogram during this period revealed persistent pancytopenia. Serum ferritin, serum triglycerides, and liver function tests were consistently deranged. Investigations for the etiology of fever and blood cultures were negative while the bone marrow aspirate revealed a normocellular marrow. CT abdomen-pelvis showed mild hepatomegaly with enlarged retroperitoneal lymph nodes. Infective endocarditis, lymphoma, and bronchopneumonia were being considered the clinical diagnoses. The significant autopsy findings were hepatosplenomegaly with retroperitoneal lymphadenopathy and multiple gastric ulcers. On microscopy, the liver, spleen, bone marrow, and lymph nodes showed characteristic hemophagocytosis. Post-mortem histopathological examination clinched the diagnosis of HLH and fulfilled six out of eight diagnostic criteria of the HLH-2004 protocol. We discuss the clinical course and diagnosis of this unique case and strive to create awareness about secondary HLH induced by common diseases, such as enteric fever.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Adult; Autopsy; Typhoid Fever; Fatal Outcome; Bone Marrow; Lymph Nodes; Liver; Spleen; Hepatomegaly
PubMed: 38391303
DOI: 10.4103/ijpm.ijpm_162_22 -
Respirology Case Reports Feb 2024In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis....
Steroid reduction-resistant pulmonary involvement with Sweet's syndrome suspected of being vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome: A case report.
In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis. A 67-year-old man who was taking prednisolone for a fever of unknown origin and Sweet's syndrome was referred to us because of an abnormal chest shadow. Computed tomography revealed a nonfibrotic hypersensitivity pneumonitis-like opacity, and blood test results indicated macrocytic anaemia. His pulmonary symptoms spontaneously improved but again exacerbated approximately 1 month later. Methylprednisolone pulse therapy improved his condition, but he had recurring fever flare and pulmonary involvement post-treatment. A peripheral blood gene test planned at a specialized institution was not performed, making the diagnosis difficult. We attempted careful tapering of methylprednisolone, but his macrocytic anaemia led to pancytopenia and he unfortunately died of sepsis due to neutropenia.
PubMed: 38384745
DOI: 10.1002/rcr2.1288 -
Journal of Cancer Research and... Oct 2023Metastatic salivary duct carcinomas (SDC) are rare tumors and evidence-based guidelines for their treatment have not yet been established. Reports of such cases like...
Metastatic salivary duct carcinomas (SDC) are rare tumors and evidence-based guidelines for their treatment have not yet been established. Reports of such cases like ours could be beneficial in the decision-making in the similar clinical circumstances. Here we present the 64-year-old Caucasian man with bone pain and pancytopenia two years after local treatment of SDC, in whom a bone marrow biopsy revealed poorly differentiated carcinoma of salivary origin with nuclear androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2/neu) positivity. Clinical response was achieved with cis-platin based cytotoxic therapy and maintenance hormonal treatment. At progression after 12 months, he was treated with anti-HER2 therapy combined with taxanes. The response lasted for 14 months. Then palliative therapy with capecitabine was introduced. With a relatively sustained quality of life, the response lasted for 15 months.
Topics: Male; Humans; Middle Aged; Receptors, Androgen; Capecitabine; Quality of Life; Salivary Ducts; Salivary Gland Neoplasms; Carcinoma
PubMed: 38376316
DOI: 10.4103/jcrt.jcrt_373_22 -
Annals of African Medicine 2023Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit...
BACKGROUND
Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit myelopoiesis and are major mediators of tissue damage. The primary goal of this study was to determine the IL-6 and IL-8 levels in children with AA, as well as their relationship to illness severity and immunosuppressive medication response.
MATERIALS AND METHODS
The IL-6 and IL-8 levels were tested in 50 children aged 3-18 years who had AA. As controls, 50 healthy age and sex matched individuals were used. A sandwich enzyme-linked immunosorbent assay kit (solid-phase) was used to measure IL-6 and IL-8 levels quantitatively. The concentrations of IL-6 and IL-8 in pg/mL were used to represent the results. Immunosuppressive medication was given to the patients in accordance with the British Committee for Standards in Haematology Guidelines 2009.
RESULTS
The patients' average age was 11.3 ± 3.7 years. Patients with AA had significantly higher IL-6 and IL-8 levels than controls (278.88 ± 216.03 vs. 4.51 ± 3.26; P < 0.001) and (120.28 ± 94.98 vs. 1.79 ± 0.78; P < 0.001), respectively. The IL-6 and IL-8 levels were also investigated with respect to AA severity, with statistically significant differences (P < 0.01) between different grading strata. Patients with very severe AA (VSAA) had the highest IL-6 levels (499.52 ± 66.19), followed by severe AA (SAA) (201.28 ± 157.77) and non-SAA (NSAA) (22.62 ± 14.63). For IL-8 levels, a similar trend (P < 0.01) was detected, with values of 209.81 ± 38.85, 92.12 ± 78.0, and 9.29 ± 10.68 for VSAA, SAA, and NSAA, respectively. After 6 months of immunosuppressive treatment (IST), mean levels of IL-6 and IL-8 in responders and nonresponders were again assessed. The mean IL-6 level in the responders' group (46.50 ± 45.41) was significantly lower, when compared to the nonresponders' group (145.76 ± 116.32) (P < 0.001). Similarly, the mean IL-8 level in the responder's group (33.57 ± 27.14) was significantly lower, compared to the nonresponder's group (97.49 ± 69.00) (P < 0.001).
CONCLUSIONS
Children with AA had higher IL-6 and IL-8 levels than normal age- and sex-matched controls. Increased levels were linked to the severity of the condition, suggesting that IL may have a role in AA. IL levels can be monitored in AA patients during IST, which can assist in predicting response to IST.
Topics: Child; Humans; Adolescent; Anemia, Aplastic; Interleukin-6; Interleukin-8; Treatment Outcome; Immunosuppressive Agents; Immunosuppression Therapy; Patient Acuity
PubMed: 38358144
DOI: 10.4103/aam.aam_106_22 -
The Journal of Veterinary Medical... Apr 2024A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically...
A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically observed. The dog had never been outside of Tokyo or Shizuoka Prefecture. Splenectomy was performed to confirm and remove the cause of splenic plasmacytosis. A histopathological diagnosis of splenic plasmacytoma was made; however, serum protein electrophoresis showed polyclonal gammopathy. Further screening was performed, and Ehrlichia canis infection was confirmed. The dog was treated with doxycycline for 5 weeks. After the antibiotic therapy, no relapse of neutropenia, thrombocytopenia, hyperglobulinemia, or positive polymerase chain reaction result of E. canis infection was observed for 3 years. Careful attention should be given to ehrlichiosis when exploring the cause of pancytopenia or hyperglobulinemia, regardless of the travel history.
Topics: Male; Dogs; Animals; Ehrlichia canis; Japan; Ehrlichiosis; Thrombocytopenia; Neutropenia; Dog Diseases; Ehrlichia
PubMed: 38355119
DOI: 10.1292/jvms.23-0486 -
Lupus Science & Medicine Feb 2024The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies...
OBJECTIVE
The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE.
METHODS
Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study.
RESULTS
(1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05).
CONCLUSIONS
(1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines.
Topics: Humans; Sirolimus; Lupus Erythematosus, Systemic; Retrospective Studies; T-Lymphocyte Subsets; Cytokines
PubMed: 38351097
DOI: 10.1136/lupus-2023-001072 -
Cureus Jan 2024Cobalamin, also known as vitamin B12, is a water-soluble vitamin. Cobalamin deficiency can be frequently seen in people all around the world. It can have non-specific... (Review)
Review
Cobalamin, also known as vitamin B12, is a water-soluble vitamin. Cobalamin deficiency can be frequently seen in people all around the world. It can have non-specific symptoms, and in patients who are in a very critical state, it can lead to neurological or hematological abnormalities. While pernicious anemia used to be the main cause, it now accounts for a smaller number of cases, with food-bound cobalamin malabsorption being more common. Early diagnosis and appropriate management are crucial to avoid severe complications like spinal cord degeneration and pancytopenia. The primary method of treatment has been injections of vitamin B12 which are given through the intramuscular route but now the oral replacement therapy has also been very effective in treating the patients. There is increasing evidence linking increased levels of vitamin B12 to hematological and hepatic disorders, particularly cancers. This review has primarily highlighted the metabolism, clinical manifestations, diagnosis, and treatment of cobalamin deficiency in the past decade.
PubMed: 38344487
DOI: 10.7759/cureus.52153 -
Proceedings (Baylor University. Medical... 2024Low-dose methotrexate has several known side effects associated with mild toxicity including nausea, oral ulcers, and anemia. However, it is rare for patients taking...
Low-dose methotrexate has several known side effects associated with mild toxicity including nausea, oral ulcers, and anemia. However, it is rare for patients taking low-dose methotrexate to present with symptoms of severe toxicity including pancytopenia, macular punctate rash, and severe stomatitis. Here we present an 83-year-old patient with a history of rheumatoid arthritis on low-dose methotrexate for 1 year presenting with 5 days of worsening facial swelling, oral lesions, and a macular rash to the extremities. Initial workup revealed severe leukopenia, thrombocytopenia, and previously undiagnosed chronic kidney injury. Computed tomography showed edema surrounding a left maxillary dental implant suggestive of infection. The patient was admitted for suspected methotrexate toxicity complicated by possible dental infection. Methotrexate was withheld. The patient's stomatitis and facial swelling improved with administration of folate, leucovorin, and piperacillin/tazobactam. The patient's severe neutropenia gradually resolved following administration of granulocyte colony-stimulating factor. Infectious workup was negative throughout admission. This case report details factors that precipitate severe methotrexate toxicity at low doses.
PubMed: 38343452
DOI: 10.1080/08998280.2023.2289299