Caroline Edijana Omoti

Richter syndrome: a review of clinical, ocular, neurological and other manifestations

Richter syndrome describes the development of high‐grade non‐Hodgkin lymphoma (NHL) or Hodgkin lymphoma in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Richter transformation occurs in 3·3 to 10·6% of patients with CLL. The large cell lymphoma clone occurs by transformation of the original CLL clone in the majority of patients, and as a separate and independent neoplasm in fewer cases. Richter transformation may be triggered by viral infections, such as Epstein‐Barr virus infection, which are common in immunosuppressed patients. Trisomy 12 and chromosome 11 abnormalities, as well as multiple genetic defects, have been described in patients with Richter syndrome. These abnormalities may cause CLL cells to proliferate and, by facilitating the acquisition of new genetic abnormalities, to transform into Richter syndrome cells. Presenting features typically include a rapid clinical deterioration with fever in the absence of infection, progressive lymph node enlargement, and an elevation in serum lactate dehydrogenase. Extranodal Richter syndrome has also been reported to occur in the central nervous system, eye, gastrointestinal system, nose, skin, face, bone and bronchus. The therapeutic options include cytoreductive therapy consisting of chemotherapy and immunotherapy, followed by allogeneic stem cell transplantation as postremission therapy.

Prevalence of parasitemia and associated immunodeficiency among HIV-malaria co-infected adult patients with highly active antiretroviral therapy

OBJECTIVE To investigate the malaria parasitemia, CD4(+) cell counts and some haematological indices among HIV-malaria co-infected adult patients with highly active antiretroviral therapy (HAART). METHODS A total of 342 adult HIV positive subjects were recruited at the consultant outpatient HIV/AIDS clinic, University of Benin Teaching Hospital, Benin City, Nigeria between June 2011 to November 2011. Blood samples were taken for malaria parasite count, CD4(+) cell count and other haematological counts. RESULTS Out of the 342 adult HIV positive subjects a total of 254 patients (74.3%) were found to have malaria parasitemia. The incidence of malaria parasitemia increased with advancing clinical stage of HIV infection and this was statistically significant (P=0.002). There was no statistical significance when gender was compared with the HIV-malaria status (P >0.05). Of the 254 co-infected patients, 134 (52.8%) had high parasitemia (>1.25 × 10(9)/L). Sixty patients were found to be hyperparasitemic (>2.5 parasites/L). There was a significant association between CD4(+) cell count and having significant parasitemia (P < 0.000 1). About half (50.8%) of co-infected patients had CD4(+) cell count ≤ 200/μL, and majority (44.9%) of this population also had significant parasitemia. Anaemia and thrombocytopenia were not significantly associated with HIV-malaria co-infection (P > 0.05). CONCLUSIONS The prevalence of parasitemia is high among the HIV/AIDS infected patients.

Ocular disorders in adult leukemia patients in Nigeria

Context: Leukemias may present with, or be associated with ocular disorders. Aims: To determine the rates of ophthalmic disorders in adult patients with leukemia. Settings and Design: A prospective study of ocular disorders in adult patients with leukemia at the University of Benin Teaching Hospital, Benin City, Nigeria, between July 2004 and June 2008 was conducted. Methods and Materials: The patients were interviewed and examined by the authors and the ocular findings were recorded. Statistical analysis was performed using Instat GraphPad™ v2.05a statistical package software. The means, standard deviation, and the Kruskal-Wallis non parametric test were performed. Results: Forty-seven patients with leukemias were seen. Nineteen patients (40.4%) had CLL, 14(29.8%) had CML, 9(19.1%) had AML and 5(10.6%) had ALL. Seven patients (14.9%) had ocular disorders due to leukemia. The ocular disorders due to the leukemia were proptosis in two patients (4.3%), retinopathy in one patient (2.1%), conjunctival infiltration in one patient (2.1%), periorbital edema in one patient (2.1%), retinal detachment in one patient (2.1%), and subconjunctival hemorrhage in one patient (2.1%). There was no significant difference in rate of the ocular disorders in the various types of leukemia (Kruskal-Wallis KW= 4.019; corrected for ties. P=0.2595). One patient (2.1%) was blind from bilateral exudative retinal detachment while 1 patient (2.1%) had monocular blindness from mature cataract. Conclusions: Ophthalmic disorders that are potentially blinding occur in leukemias. Ophthalmic evaluation is needed in these patients for early identification and treatment of blinding conditions.

Pharmacological strategies for the management of cancer pain in developing countries

Pain associated with cancer is often under treated especially in the developing countries where there are problems of poor economy, poor purchasing power of the citizens, absence of effective national health insurance schemes, poor manpower, fake adulterated and expired drugs, poor drug storage conditions; adverse temperature conditions combined with poor power supply which may affect drug efficacy. There is also poor understanding of the physiopharmacology of cancer pain management by health care providers. Assessment of the severity of the pain by location, oncological type, as well as psychosocial, emotional and environmental factors are necessary. The pain often occurs from malignancy, from procedures done to diagnose, stage and treat the malignancy, and from the toxicities of therapy used in treating the cancer. The first priority of treatment is to control pain rapidly and completely, as judged by the patient. The second priority is to prevent recurrence of pain. Analgesic drugs are given ‘by the ladder,’ ‘by the clock’ and ‘by the appropriate route’ using the analgesic ladder guideline proposed by the World Health Organization (WHO). The pharmacological aspects of various drugs used in the management of cancer pain are discussed.

The role of Epstein–Barr virus in Richter syndrome: response to Nourse et al

We wish to thank Nourse et al for their valuable comments on our article, ‘Richter’s syndrome: A review of clinical, ocular, neurological and other manifestations’ (Omoti & Omoti, 2008), which helps to put some of the issues concerning the role of Epstein–Barr Virus (EBV) in the aetiology of Richter’s syndrome in the right perspective. Although several review and original articles have focussed on the aetiology of Richter’s syndrome, our article summarized some sections, such as aetiology, and focussed on the systemic manifestations that have not been reviewed by other articles. In summarizing the aetiology, certain aspects may have been simplified. Definitely, Richter’s transformation represents a complex multistep process and, although viral associations have been identified, integration of the available scientific data poses substantial questions. Concerning the cell type that is primarily infected by EBV, a model for EBV persistence has been proposed as follows (Hochberg et al, 2004): Virions enter the mucosal surface of the nasopharynx through saliva. The virus enters the lymphoid tissue of Waldeyer’s ring, where it infects resting naive B cells and drives them to become proliferating lymphoblasts through expression of nine latent proteins (the growth program). These blasts can then differentiate into resting memory cells through a process analogous to the germinal centre (GC) reaction by using the default program. Once in resting memory cells, all viral protein expression ceases (the latency program). Latently infected memory cells circulate in the periphery and return to the lymphoid tissue, where at some unknown rate, they differentiate into plasma cells and release infectious virus to initiate a new round of infection. Each stage of the cycle is subject to immunosurveillance (cytotoxic T lymphocytes against infected cells and antibody against virions), with the exception of the memory cells, which are invisible because they express no viral proteins. In the absence of an immune response, the cycle will amplify until the memory B compartment is filled with latently infected cells. Once the immune response is activated, the cycle is dramatically reduced or perhaps even completely blocked and the reservoir of latently infected memory cells decays. There are now recent studies that propose this model or something very similar (Klein & Dalla-Favera, 2008). However, other studies seem to differ from this model (Kurth et al, 2000, 2003). These studies on acute infectious mononucleosis tonsils have led to the suggestion that EBV may establish persistent infection in the memory compartment by direct infection. EBV-driven clonal expansion of naive B cells was not seen in these studies. In infectious mononucleosis, GC and/or memory B cells were found to be directly infected by EBV and expand without somatic hypermutation, whereas the GC passage of EBV-infected naive B cells does not contribute detectably to the generation of infected memory B cells, the main reservoir of EBV during persistence (Kurth et al, 2003). One limitation of several studies is that patients are only tested when they present to the clinic. It is possible that during the very early stages of the infection, before the onset of symptoms, multiple cell types are infected in the blood. Subsequently, the infection could become restricted to memory cells by the time of onset of symptoms, when the patients are first studied (Hochberg et al, 2004). Another limitation with immunohistochemical approaches to identify infected cells in vivo is that the lower threshold for detection is not known (Hochberg et al, 2004). Thus, it is impossible to know how many infected cells have been missed and how representative the identified cells are. It is clear that the precise role of EBV infection in Richter’s syndrome remains to be established. What is not in doubt however is that the memory cells are the site of long-term persistent infection. Advances in technology have allowed a more precise dissection of the phenotypes of GC B cells and the specific transcriptional programmes that are responsible for this phenotype, as well as understanding of the mechanism controlling the exit of B cells from the GC and the decision to become a memory B cell or plasma cell (Klein & Dalla-Favera, 2008). Further advances are required to fully establish the precise role of EBV in the aetiology of Richter’s syndrome.