Gaucher Disease: A First Reported Adult Case in Indonesia.

A 44-year-old female presented with a distended abdomen and fatigue. On physical examination, prominent splenomegaly was found. The laboratory investigations revealed pancytopenia and decreased albumin-globulin ratio. The abdominal ultrasonography revealed splenomegaly, cholelithiasis, and cystitis, and the bone survey showed osteopenia. Differential diagnoses included leukemia, multiple myeloma, and myelofibrosis therefore bone marrow puncture was performed. However, histopathologic examination found Gaucher-like cells in the bone marrow aspiration. The finding of CD68 positivity in Gaucher-like cells by using the immunohistochemistry staining supporting Gaucher disease. To confirm the diagnosis, an examination of glucocerebroside substrate from the patient's blood plasma was performed. Glucosylsphingosine, a deacylated form of glucosylceramide, was markedly elevated. Therefore, the diagnosis of Gaucher disease was confirmed. This is the first reported adult Gaucher case diagnosed in Indonesia.

Assessing Long-Term Neurologic Outcomes in SAMD9L-Related Ataxia-Pancytopenia Syndrome.

BACKGROUND: Most published reports on SAMD9L-related ataxia-pancytopenia syndrome (ATXPC) have emphasized the hematologic findings. Fewer details are known about the progression of neurologic manifestations and methods for monitoring them. CASES: We present six individuals from two families transmitting a heterozygous variant in SAMD9L, exhibiting clinical variations in their hematologic and neurologic findings. Serial motor function testing was used to monitor motor proficiency over a 2 to 3 year period in the proband and his father from Family 1. CONCLUSIONS: Our case series focuses on the neurologic progression in patients with heterozygous variants in SAMD9L. Patients with ATXPC should be followed to evaluate a wide range of neurologic manifestations. Serial motor function testing using a standardized method is helpful to track changes in balance and coordination in children and adults with ATXPC and could aid in a future extended natural history study.

Management of granulomatosis with polyangiitis complicated by intestinal perforation and pancytopenia: a case report and literature review.

Granulomatosis with polyangiitis is a systemic vasculitis. While the classic triad typically comprises otorhinolaryngologic, pulmonary, and renal manifestations, it is essential to recognize that granulomatosis with polyangiitis can affect any organ. Furthermore, reports have documented less common sites of involvement, such as the gastrointestinal tract. In this case-based review, we focus on a case of granulomatosis with polyangiitis presenting with intestinal perforation and the added challenge of concurrent pancytopenia.A 25-year-old female was diagnosed with granulomatosis with polyangiitis, with her clinical course progressing from joint pain to severe multi-organ involvement, including gastrointestinal complications. Treatment challenges emerged with the development of pancytopenia. While this may not directly result from granulomatosis with polyangiitis, it introduced an additional layer of complexity and delayed the induction of remission with immunosuppressants. Despite initial stabilization, an unexpected jejunal perforation occurred, requiring surgical intervention and subsequent postoperative care. The case underscores the complex nature of granulomatosis with polyangiitis and its potential complications. A literature search yielded discrete relevant cases in the context of our patient's intricate presentation, which has been summarized.We highlight the complexities in diagnosing and managing granulomatosis with polyangiitis-related complications, especially in uncommon presentations, and emphasize the importance of a personalized approach to patient care in these circumstances.

Gelatinous bone marrow with vivid fatty cells.

We treated a 78-year-old Japanese man with gastric diffuse large B cell lymphoma. The patient received three courses of chemotherapy and involved-field local radiation therapy to the stomach. Three years after chemotherapy, the patient become sick with anorexia and pancytopenia. He was cachexic, however, levels of vitamin B12, folate, zinc, and copper were normal. His bone marrow revealed focal eosinophilic deposit characterized by mixture of vivid atrophic fatty cells, which was pathologically diagnosed as gelatinous bone marrow. The patient's gelatinous marrow was characterized by CD68-stained vivid atrophic fatty tissue. We found that this finding is a possible alternative marker for gelatinous marrow.

Human Herpesvirus-8 (HHV-8)-Positive Human Immunodeficiency Virus (HIV)-Negative Multicentric Castleman Disease With a Fulminant Course.

Multicentric Castleman disease (MCD) is a poorly understood, heterogeneous lymphoproliferative disorder with benign hyperplastic lymph nodes and systemic inflammatory symptoms. Human herpesvirus-8 (HHV-8) may be associated with MCD, whether or not the patient is infected with the human immunodeficiency virus (HIV). A 74-year-old man presented with anaemia, thrombocytopenia and bilateral axillary adenomegaly of unknown origin. The patient was admitted to the hospital two years ago with clinical signs of weight loss, asthenia, anorexia and a maculopapular rash on the trunk and back. Blood analysis showed pancytopenia (haemoglobin 7.7 g/dL, leucocytes 2.55 x 109/L and platelets 41 x 109/L), elevated acute phase reactants (such as C-reactive protein, erythrocyte sedimentation rate, ferritin and fibrinogen), hypoalbuminemia and hypergammaglobulinemia, and HIV serology was negative. Thoracic, abdominal and pelvic axial tomography showed generalised lymphadenopathy. The bone marrow biopsy showed only reactive changes, and the histology of an excisional biopsy of the adenopathy was consistent with the plasmablastic variant of MCD associated with HHV-8. The HHV-8 viral load was 3.8 x 104 copies/mL (4.5 log). He was started on prednisolone 60 mg/day and rituximab. He had a poor response to therapy, despite a reduction in the HHV-8 viral load, with clinical deterioration, transfusion-dependent anaemia and progression to multi-organ dysfunction leading to death three weeks after starting treatment. Our patient had a fulminant course of MCD despite treatment with rituximab. Further studies are needed to validate the different treatment modalities and to better understand the prognosis of this disease.

Unusual Presentation of Corynebacterium Endocarditis in a Patient Without Conventional Risk Factors: A Case Report.

Infective endocarditis (IE) is a widespread condition marked by the infection of native or prosthetic heart valves, the endocardial surface, or an indwelling cardiac device. While native-valve IE is uncommon, patients with IE represent a diverse spectrum. Some respond well to treatment with few complications, while others face severe complications and an increased risk of mortality. Various factors contribute to this outcome, including delayed diagnosis, underlying health conditions like immunocompromised status or chronic diseases, and intravenous drug use. The most prevalent causes of IE are typically streptococci and staphylococci. IE attributed to Corynebacterium species is an exceptionally rare phenomenon, especially in individuals lacking conventional risk factors. This report presents a distinctive case involving Corynebacterium endocarditis in a 63-year-old female with a medical history encompassing intracranial aneurysm, hypothyroidism, and alcoholic cirrhosis. The patient's initial symptoms included shortness of breath, neck pain, and generalized weakness. Despite an initial focus on mild flu-like symptoms and a suspected urinary tract infection, subsequent evaluation unveiled pancytopenia and positive blood cultures for Corynebacterium striatum, culminating in the diagnosis of mitral valve endocarditis. This intricate clinical scenario, replete with numerous complications, underscores the significance of considering unusual pathogens in atypical presentations of IE. It prompts further exploration into the underlying mechanisms contributing to such infrequent occurrences.

Aplastic Anaemia Associated with Bendamustine Therapy - A Rare Side Effect.

Introduction: During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma. Case description: A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO® regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal. Conclusions: This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia. LEARNING POINTS: Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights.

Objective: The study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database. Methods: The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification. Results: The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-α and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C>T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as "Likely pathogenic". Currently, there are no reports in academic literature regarding this specific variant site. Conclusion: LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C>T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.

Pancytopenia following adjuvant therapy with interferon-gamma in a patient with disseminated nocardiosis.

A patient with disseminated nocardiosis developed pancytopenia after treatment with recombinant interferon-gamma (IFN-γ). While no previous clinical reports link pancytopenia to IFN-γ, our observations align with basic research on myelosuppressive effects of IFN-γ. Adjunctive IFN-γ may improve standard nocardiosis therapy, but vigilant monitoring of its hematologic effects is necessary.

[Bone marrow histology of cytopenias : Contribution to hematological differential diagnosis]. / Knochenmarkhistologie bei Zytopenien : Beitrag zur hämatologischen Differenzialdiagnostik.

Besides microscopic evaluation of smears, flow cytometric analysis, chromosomal and molecular studies, histological analysis of bone marrow biopsies (BMbx) is an important component of multiparameter diagnostics of cytopenias in hematology. More than in other fields of histopathology, correct interpretation of BMbx requires correlation with the results of these further studies and other clinical findings. Microcytic, normocytic and macrocytic anemia, isolated granulocytopenia and thromobocytopenia as well as pancytopenia represent frequent and recurrent diseases. With regard to aetiology, reactive and neoplastic causes must be differentiated. Reactive causes of cytopenia include substrate deficiencies, enhanced turn over and loss, and inflammatory processes. Neoplastic disorders with the exception of myeloproliferative neoplasms generally manifest as cytopenia and comprise myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and lymphoma.

Low-dose methotrexate toxicity leading to pancytopenia: leucovorin as a rescue treatment.

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.

New-Onset Monosomy 7-Induced Pancytopenia in a 66-Year-Old Woman.

Myelodysplastic syndrome (MDS) is characterized by failure to initiate hematopoiesis or impaired maturation of cells, often presenting with pancytopenias with or without associated fatigue, infections, or inappropriate bleeding and bruising. Karyotype analyses of MDS patients commonly show deletion of the q arm of chromosome 7, suggesting loss of this region is likely implicated in the insufficient hematopoiesis seen in MDS. The predisposition to deletion of 7q is commonly inherited, with clinical presentation in early childhood associated with pancytopenia or hematological malignancy. In this case, we present a 66-year-old female who was incidentally found to be pancytopenic in the emergency department while being evaluated for dyspnea, with a bone marrow biopsy later confirming a diagnosis of MDS with monosomy 7. Sporadic loss of 7q can occur at any stage in life without any family history of hematological disease. Our patient has no known personal or family history of MDS, with normal blood counts during hospitalization three years prior, suggesting de novo loss of 7q occurring at greater than 60 years of age.

The Outcome of Aplastic Anaemia Associated with Terbinafine Therapy.

Onychomycosis (OM), a widespread fungus that affects the toenails and/or fingernails, causes a large amount of morbidity and is very frequent in the general population. The best treatment is systemic antifungals. Terbinafine is a potent antifungal drug that works by targeting the keratin and lipids found in fungi. In the United States, the prevalence of this nail ailment ranges from 2% to 14%; it is 5.5% globally. Here, we describe a case of aplastic anaemia linked to oral terbinafine use. Clinicians should be aware of this rare adverse effect and early discontinuation of the treatment is required to prevent significant morbidity and mortality. LEARNING POINTS: Aplastic anaemia is a rare side effect of terbinafine.Patients should be advised about this, and serial laboratory testing can be helpful for those who are on a long-term course of terbinafine.Early diagnosis and start of treatment can lead to a favourable outcome.

Caroli disease combined with Banti syndrome in a woman: a case report.

Caroli disease is a rare congenital malformation that predisposes to segmental cystic dilatation of the intrahepatic bile ducts. Banti syndrome is characterized by persistent splenomegaly due to chronic congestion, resulting in a low hematocrit and ultimately leading to pancytopenia. In this report, we describe a 29-year-old woman who presented with a >20-year history of hepatitis B surface antigen positivity and a >1-year history of recurrent fatigue and malaise. On examination, the patient had abdominal distension with marked splenomegaly (7 cm below the ribs) and ascites with tenderness of the abdominal muscles to palpation. A complete blood count showed a low white blood cell count, red blood cell count, and hemoglobin concentration. During the course of treatment, the patient developed multiple symptoms of pancytopenia and concomitant splenomegaly, and she was discharged after total splenectomy with good recovery. The combination of Banti syndrome and Caroli disease results in severe symptoms of portal hypertension.

Graves' disease with pancytopenia: A rare case report.

Key Clinical Message: In this case report we describe a patient with Grave's disease (GD) who was first diagnosed with pancytopenia and did not have any typical symptoms of GD. His hematologic abnormalities were alleviated after treatment with an anti-thyroid drug. Hence, in patients with pancytopenia, GD should also be considered. Abstract: A variety of hematologic abnormalities can be seen in Graves' disease (GD), however; here, we describe a patient with GD and a very rare complication; pancytopenia. His hematologic abnormalities and clinical status were alleviated after treatment with an anti-thyroid drug. Hence, in patients with pancytopenia and normal bone marrow examination, GD should also be considered.

Visceral leishmaniasis misdiagnosed as an upper respiratory infection and iron-deficiency anemia in a 20-month-old male patient: a case report.

BACKGROUND: Visceral Leishmaniasis should be suspected in every patient with a history of splenomegaly, fever, and pancytopenia. It is one of the most dangerous forms of infection and prompt recognition is the key to positive outcome. CASE PRESENTATION: A 20-month-old Caucasian male patient was brought to our hospital as an outpatient with the complaint of persistent fever, which did not improve with empiric antibiotic treatment (> 96 hour after the initial dose). The antibiotic treatment had been prescribed by primary care physician at polyclinic, who also referred the patient to hematologist due to anemia, who prescribed iron supplement. Despite multiple subspecialist visits, bicytopenia was, unfortunately, left unidentified. Upon physical examination no specific signs were detected, however, spleen seemed slightly enlarged. Patient was admitted to the hospital for further work-up, management and evaluation. Abdominal ultrasound, complete blood count and c-reactive protein had been ordered. Hematologist and infectionist were involved, both advised to run serology for Epstein-Barr Virus and Visceral Leishmaniasis. The latter was positive; therefore, patient was transferred to the specialized clinic for specific management. CONCLUSION: Both in endemic and non-endemic areas the awareness about VL should be increased among the medical professionals. We also recommend that our colleagues take the same approach when dealing with bicytopenia and fever, just as with pancytopenia and fever. The medical community should make sure that none of the cases of fever and pancytopenia are overlooked, especially if we have hepatomegaly and/or splenomegaly.

Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.

Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.