Immunology is a discipline that traverses all branches of clinical medicine. Thus since about ten years ago major hospitals in Malaysia established routine clinical immunology services particularly in the diagnosis of autoimmune/connective tissue disorders. More recently these laboratories have ventured into basic research in Dengue Haemorrhagic Fever, Leukaemia Immunology, Nasopharyngeal Cancer and Leprosy. The rationale for these projects together with early results from them are discussed.
Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes are often the presenting features of the POEMS syndrome. Approximately 50% of these are associated with osteosclerotic myeloma, a rare variant of multiple myeloma and some with Castleman's disease, an unusual lympho-proliferative disorder. The underlying pathogenetic mechanisms have not been elucidated but amelioration of symptoms with the disappearance of the M-component suggests possible etiopathogenic mechanisms. We present a 40-year-old woman with manifestations of all three disorders.
A young patient presenting with splenomegaly and hypersplenism was inadvertently found to have selective IgA deficiency. There were no symptoms of immunodeficiency and the patient responded well to splenectomy, with return of blood counts to normal without adverse effects. No other cause for the hypersplenism was found. We postulate selective IgA deficiency as a cause of splenomegaly and hypersplenism.
A 26-year-old male presented with claw toes and Factor XIII deficiency. Correction for his deformity was undertaken. Pre, intra and post-operative transfusions of plasma and blood prevented any haemorrhagic complications.
Chronic lymphocytic leukaemia (CLL) is rare locally. Seven CLL patients which constituted 0.9% of the total 747 cases of leukaemic patients were diagnosed over a 5 year period. They had similar haematological profiles as Western patients though most of them had advanced disease at presentation. Treatment of CLL patients was palliative and should be reserved for symptomatic patients and/or patients with progressive disease.
Forty-six Malaysian patients with chronic granulocytic leukaemia were found to be rearranged in the breakpoint cluster region (BCR) of chromosome 22, molecular evidence of Philadelphia chromosome (t9.22) translocation. Through the use of a 1.2 kb 3' BCR probe and two restriction enzyme digests, patients' breakpoints could be localized either to 5' or 3' regions of the BCR. Breakpoint site localization at the time of DNA sampling did not show any positive statistical association to clinical status defined as chronic phase, chronic phase with less than 6 months to blast crisis, accelerated phase and blast crisis. This was in contrast to earlier reports which indicated that patients with breakpoint at 3' site were at a higher biologic risk for entering blast crisis.
An immunofluorescence test (IFT) using platelet suspensions was used to detect the presence of serum anti-platelet antibodies (APA) in the sera of Malaysian patients with idiopathic thrombocytopenic purpura. Of the 28 patients tested, 19 (or 68%) had detectable APA with percentage platelet fluorescence ranging from 34% - 80% (mean 51% +/- 10). Normal sera gave fluorescence values of 6 - 15% (mean 9% +/- 5). Sera from patients with SLE, thyrotoxicosis and dengue haemorrhagic fever gave mean values of 29%, 8% and 9% respectively. Additionally, no apparent correlation was observed between percentage platelet fluorescence and the severity of thrombocytopenia. The importance and significance of these findings are discussed.
Rearrangements in the DNA of chronic myelogenous leukemia patients of Chinese, Malay and Indian origin were detected in the breakpoint cluster region of chromosome 22 using molecular techniques. The DNA of fifty patients was examined using a 1.2 kb DNA probe. Rearrangements were detected in 46/50 patients. Karyotypic data were available in nine patients, all of whom were Philadelphia chromosome positive and exhibited DNA rearrangement. Detection of the Philadelphia translocation by molecular methods, at this institution, where cytogenetics is not routinely performed, confirms its diagnostic value. The rearrangement data obtained in this study is consistent with molecular features of chronic myelogenous leukemia patients of Western countries.
Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.
Ninety-two women with systemic lupus erythematosus treated with oral cyclophosphamide were studied to ascertain the prevalence and the factors associated with ovarian dysfunction. Menstrual disturbance during treatment occurred in 55% of patients: 36% had amenorrhoea and 19% had oligomenorrhoea. Sustained oligomenorrhoea occurred in 12% patients. Permanent amenorrhoea (> 12 months) after cessation of oral cyclophosphamide occurred in 27% of patients. Hormonal studies in these patients were consistent with ovarian failure. Older age at initiation of treatment and high cumulative dose of cyclophosphamide were found to be associated with this outcome. There was a trend towards linear relationship between the age of initiation of cyclophosphamide therapy and frequency of amenorrhoea. A statistically significant association between amenorrhoea and cumulative dose of cyclophosphamide after adjustment for age was found whereas no such association was linked to the duration of treatment. Fourteen of the 23 women who wished to become pregnant after cessation of treatment conceived resulting in 20 live births and two abortions.
Pregnancy following idiopathic aplastic anaemia is rare and is difficult to manage because of life-threatening episodes of bleeding and infections. Only a handful of cases has been reported in the literature. The pregnancies were unsuccessful in the majority. The present report describes a patient with moderately severe idiopathic aplastic anaemia who was managed with intensive haematological support leading to delivery of a healthy infant by caesarean section. Despite platelet transfusion refractoriness as a result of transfusions prior to pregnancy, adequate platelet transfusions prevented excessive bleeding. The literature is reviewed and management with platelet transfusions is discussed.
Acute aortic thrombosis is a rare condition, occurring mainly as a result of trauma or atherosclerosis and occasionally secondary to hypercoagulable states. We report a patient with relapsed acute myeloid leukaemia who developed an unusual complication, acute aortic thrombosis.
Deoxyribonucleic acid (DNA) of twenty chronic myeloid leukemia (CML) and thirty acute lymphoblastic leukemia (ALL) patients were analysed by Southern hybridization. The DNA was digested with BglII and hybridized with a 4.5-kilobase (kb) ph1/bcr-3 DNA probe. All the 20 CML patients showed gene rearrangement within a 5.8-kb segment (the major breakpoint cluster region, M-bcr) of the breakpoint cluster region (bcr) gene of chromosome 22, indicating the presence of the Philadelphia chromosome. M-bcr rearrangement at the bcr gene of chromosome twenty-two was not detected in all the thirty ALL patients (nine adults and twenty-one children) and two normal controls.
A typical case of chronic pericardial effusion resulting in cardiac tamponade is presented. A pericardiocentesis was done for diagnosis and drainage, followed by a pleuro-pericardial window as definitive therapy. The minimal cumulative dose expected to produce pericardial disease is about 4000 rads, and the disease usually manifests within 12 months of such radiation exposure, as in this patient. It is concluded that for symptomatic pericardial effusions, available evidence justifies a subtotal pericardiectomy, a window procedure being reserved to tide over ill patients as in this patient. No strong evidence exists for the efficacy of steroid therapy; such therapy is reserved for asymptomatic mild effusions, which may also resolve spontaneously.