ABSTRACT
BACKGROUND: Ethanol dependence is associated with a discontinuation withdrawal delirium. Chlordiazepoxide is frequently successfully used in its treatment. CASE PRESENTATION: A 27-year-old, Caucasian female with ethanol dependence who had objective symptoms of withdrawal experienced worsening of her delirium after administration of chlordiazepoxide, but improved with lorazepam and cleared with discontinuation of benzodiazepine administration. CONCLUSIONS: Worsening of delirium appears to be related to the specific use of chlordiazepoxide, but the mechanism of this effect is not clear. While this case does not alter the standard care of ethanol dependence, it does alert clinicians that our treatment approach may not be fully benign.
Subject(s)
Alcoholism , Delirium , Substance Withdrawal Syndrome , Adult , Alcoholism/complications , Chlordiazepoxide , Delirium/chemically induced , Delirium/complications , Ethanol/adverse effects , Female , Humans , Substance Withdrawal Syndrome/drug therapyABSTRACT
Primary immune thrombocytopenia is an acquired autoimmune disorder characterized by platelet count of <100 × 10(9)/l in the absence of other causes of thrombocytopenia. Primary immune thrombocytopenia is defined as 'chronic' when it has been present for more than 12 months without spontaneous remission or maintenance of complete response to therapy. Recently, thrombopoietin receptor agonists became available for treatment of chronic primary immune thrombocytopenia. Anecdotal reports have raised concerns about a possible association between therapy with thrombopoietin receptor agonists and an increase in bone marrow fibrosis. To investigate this association we studied eight patients with primary immune thrombocytopenia in detail comparing fibrosis and other morphological features in pre-therapy and on-therapy bone marrow biopsies, with the longest follow-up reported to date. A slight but significant increase to MF-1 in reticulin fibrosis was observed during therapy, but collagen was never present. On-therapy bone marrows were hypercellular due to panmyelosis with increased trilineage hematopoiesis. Megakaryocytes were increased in number, with acquisition of evident pleomorphism, nuclear hyperlobulation and tendency in some cases to form clusters. The overall picture of the on-therapy marrows was characterized by myeloproliferative neoplasm-like features, resembling essential thrombocythemia or occasionally early primary myelofibrosis. As thrombopoietin receptor agonists are becoming a mainstream treatment for primary immune thrombocytopenia, general pathologists and especially hematopathologists need to be aware of the characteristic morphological changes associated with use of these therapeutic agents, in order to avoid misdiagnosis of a myeloid neoplasm.
Subject(s)
Bone Marrow Cells/drug effects , Immunologic Factors/adverse effects , Primary Myelofibrosis/chemically induced , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Receptors, Thrombopoietin/agonists , Reticulin/analysis , Stromal Cells/drug effects , Adolescent , Adult , Aged , Biomarkers/analysis , Biopsy , Bone Marrow Cells/chemistry , Bone Marrow Cells/pathology , Bone Marrow Examination , Child, Preschool , Extracellular Matrix Proteins/analysis , Female , Humans , Immunohistochemistry , Male , Megakaryocytes/chemistry , Megakaryocytes/drug effects , Megakaryocytes/pathology , Middle Aged , Primary Myelofibrosis/metabolism , Primary Myelofibrosis/pathology , Purpura, Thrombocytopenic, Idiopathic/metabolism , Purpura, Thrombocytopenic, Idiopathic/pathology , Receptors, Thrombopoietin/metabolism , Stromal Cells/chemistry , Stromal Cells/pathology , Time Factors , Treatment OutcomeABSTRACT
Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.
