Occurrence Of Severe Manifestations Research Articles

Mevalonate Kinase-Associated Diseases: Hunting for Phenotype-Genotype Correlation.

Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene (MVK) and encompass several phenotypically different rare and hereditary autoinflammatory conditions. The most serious is a recessive systemic metabolic disease called mevalonic aciduria, and the most recently recognized is disseminated superficial actinic porokeratosis, a dominant disease limited to the skin. To evaluate a possible correlation between genotypes and (1) the different MKAD clinical subtypes or (2) the occurrence of severe manifestations, data were reviewed for all patients with MVK variants described in the literature (N = 346), as well as those referred to our center (N = 51). The genotypes including p.(Val377Ile) (homozygous or compound heterozygous) were more frequent in mild systemic forms but were also sometimes encountered with severe disease. We confirmed that amyloidosis was more prevalent in patients compound heterozygous for p.(Ile268Thr) and p.(Val377Ile) than in others and revealed new associations. Patients homozygous for p.(Leu264Phe), p.(Ala334Thr) or compound heterozygous for p.(His20Pro) and p.(Ala334Thr) had increased risk of severe neurological or ocular symptoms. All patients homozygous for p.(Leu264Phe) had a cataract. The variants associated with porokeratosis were relatively specific and more frequently caused a frameshift than in patients with other clinical forms (26% vs. 6%). We provide practical recommendations focusing on phenotype–genotype correlation in MKAD that could be helpful for prophylactic management.

The use of hydroxyurea in sickle cell disease: A single tertiary centre experience at the National Hospital, Abuja, Nigeria

Background. Hydroxyurea (HU) has been found to be beneficial in sickle cell disease (SCD), reducing the occurrence of severe manifestations of the disease such as painful crises and blood transfusions. Although a standard of care for SCD in the developed countries of the world, limited data are available on its use in Africa. Objectives. To review indications of the use of HU, laboratory monitoring and outcome in children with SCD. Methods. A retrospective review of 74 patients treated with HU (15 - 30 mg/kg/day) for a minimum of 6 months. The main outcome measures were indications for use of HU, haemoglobin level (Hb), packed cell volume (PCV), white cell count (WBC), absolute neutrophil count (ANC), serum alanine aminotransferase (ALT) and creatinine. Descriptive statistics were expressed as means ±2 standard deviations. Data were compared pre and post HU therapy, using the chi-square and Student’s t -test as appropriate. Results. The 74 patients constituted 7.26% of the SCD clinic population and were aged 2.25 - 16 years (mean (SD) 8.48 (3.67)) and were on HU therapy for 0.5 - 4.8 years (mean (SD) 1.72 (1.12)). The haemoglobin genotypes were Hb SS 72 (98.7%); Hb SC and Hb SS+F 1 (1.35%) each. Indications for HU use were abnormalities of transcranial Doppler ultrasound (TCD) 39 (52.7%), multiple vaso-occlusive crises (VOC) 18 (24.3%), strokes 14 (18.9%), as well as repeated blood transfusions 9 (12.2%) and hospital admissions 7 (9.5%). Some patients had more than one indication. There were significantly fewer TCD abnormalities, VOC, strokes, splenic sequestrations, blood transfusions and hospital admissions following use of HU. The mean Hb and PCV increased while WBC and ANC decreased. Occurrence of acute chest syndrome, priapism, serum creatinine, ALT and platelet levels were not affected. Conclusions. Hydroxyurea therapy reduces the occurrence of severe manifestations and improves laboratory parameters in children with SCD.

Herpetic Oral Manifestation In Acute Myeloid Leukemia: case report

Viral infections in the oral cavity are frequent complications in patients with immunosuppression. The herpes simplex virus is among the most frequent causes of these infections. In immunocompromised patients the presentation may be atypical, with more extensive lesions, painful and with slower recovery. The goal of this article is to present a illustrative case of herpes oral infection in an immunosuppressed patient. Case report: Female patient, 43 years old, 32 days after the start of chemotherapy for acute myeloid leukemia, began complaining of odynophagia and painful emergence of lesions in the oral cavity. She presented multiple whitish ulcerated lesions with an erythematous halo, measuring around 0.5 cm in diameter across the mouth and the posterior wall of oropharynx. Treated with acyclovir with rapid improvement of symptoms and lesions. Cytological changes were found compatible with herpes simplex. Discussion: In most cases of infection with herpes simplex the presentations are self-limited but severe infections may occur and atypical in immunosuppressed individuals. Additional exams help in diagnosis as diagnostic cytology, ELISA and direct immunofluorescence. Acyclovir is the drug of choice for the treatment recommended dose of 1 g/day for a minimum period of 10 days. Conclusion: The oral lesions of herpes virus in immunosuppressed patients may have varied presentations and can often go unnoticed, as in mild or asymptomatic cases. However, due to the possibility of systemic spread of infection and the occurrence of severe manifestations, one should be highly suspected before the appearance of any oral lesion in the immunosupressed patients.

Mycophenolate mofetil and systemic lupus erythematosus

Mycophenolate mofetil (MMF) is an immunosuppressive agent which provides protection against acute transplant rejection, in patients who undergo kidney, heart and liver transplantation. Recently MMF has been used in various autoimmune conditions, including systemic lupus erythematosus (SLE). In SLE, MMF has been more extensively used in the treatment of proliferative lupus glomerulonephritis (GLN) and following the success in this field, it has also been used to control extra-renal manifestations. However, in the majority of cases MMF was administered to patients with refractory SLE manifestations and, therefore, no definite conclusion could be drawn from these experiences. In this paper, after a brief description of the mechanisms of action, the pharmacokinetics and metabolism of MMF which are relevant in SLE, and after a short discussion on the utility of performing therapeutic dose monitoring of mycphenolic acid, the experiences with the use of this drug in the different SLE manifestations were summarized and some personal data in patients with GLN were reported. Finally, the hypothetical use of MMF as a preventive strategy against the occurrence of severe manifestations in patients with mild SLE has been put forward and discussed.