Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Translocational rearrangements of 11q23 in acute monoblastic leukemia.

We report the rearrangements of 11q23 in the form of t(6;11)(q27;q23) and t(11;16)(q23;q24) in three cases of acute monoblastic leukemia. The former translocation had only previously been reported in five cases of acute myeloid leukemia, while the latter is hitherto undescribed. In addition to describing a new chromosomal locus 16q24, which may participate in translocational exchanges with 11q23, this report also confirms the close association between 11q23 rearrangement and the involvement of the monocytic lineage in acute myeloid leukemia.

Central nervous system involvement in non-Hodgkin's lymphoma.

Fifty-eight Hong Kong Chinese patients with CNS lymphoma were reviewed (primary seven, secondary 51). The incidence of secondary CNS lymphoma in patients with non-Hodgkin's lymphoma was estimated to be 9.4%. The Working Formulation separated subtypes which had a special propensity to involve the CNS. Significant proportions of our patients with secondary CNS lymphoma had other features which were known to be associated with a high risk of CNS disease including stage IV (48/51, 91.4%), bone marrow (26/51, 50.9%), peripheral blood (7.51, 13.7%), nasal (7/51, 13.7%), orbital (3/51, 5.9%), testicular (2/51, 3.9%) and bulky retroperitoneal (6/51, 11.8%) disease. 82% of patients with secondary CNS lymphoma had concurrent systemic disease and a further 12% had systemic relapse shortly afterward. CNS lymphoma is associated with poor prognosis and only 29% and 14% of the patients with primary and secondary CNS lymphoma respectively survived beyond 1 year. Patients responding to therapy had significantly better survival. 69.9% of the deaths were related to progressive systemic disease.

Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy.

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.

Acute lymphoblastic leukemia in Chinese adults in Hong Kong.

Forty-four previously untreated Chinese adult patients with acute lymphoblastic leukemia (ALL) were treated with vincristine, adriamycin and prednisone with or without L-asparaginase. The clinical features and prognostic factors were similar to those reported in Caucasian series. Overall complete remission (CR) rate was 52%. Duration of first remission and overall median survival were nine and 12 months respectively. The addition of L-asparaginase did not improve CR rate or duration of remission and was associated with clotting dysfunction and other adverse reactions. Factors associated with a higher CR rate include age less than 40 years, blast count less than 10 x 10(9)/l and CALLA + phenotype at presentation. Sex, platelet count and FAB morphology did not affect CR rate. Bone marrow relapse occurred in 11 patients and was associated with short survival after relapse (median two months; mean two months; range 0.5-7 months). Central nervous system relapse occurred in four patients and was compatible with relatively long survival after relapse (median 13 months; mean 12 months; range 6-12 + months). The poor CR rate and short median survival in this study could not be adequately explained by an increase in risk factors and is likely to be due to what is currently regarded as suboptimal chemotherapy.

Is hypereosinophilic syndrome a malignant disease?

A patient with an abdominal mass for 4 years developed hypereosinophilia and weight loss. Bone marrow aspirations and biopsy specimens showed hypercellularity of eosinophils. No cause for hypereosinophilia was found. Biopsy specimens of several organs, including the abdominal mass, showed eosinophilic infiltration with reactive fibrosis in some. Cytogenetic studies of the bone marrow before treatment with cytoxic drugs showed chromosomal abnormalities. Several of these have been reported in association with acute or eosinophilic leukemias. Based upon these findings, the authors believe that the patient had eosinophilic leukemia and that the abdominal mass probably was an eosinophilic chloroma.

Iron overload in thalassaemic patients in Hong Kong.

Body iron status, as measured by serum ferritin, was studied in 101 adult Chinese thalassaemic patients, 46 males and 55 females. Thirty of them had mild disease (beta thalassaemia trait), 56 disease of intermediate severity (haemoglobin H disease) and 15 severe disease (homozygous beta thalassaemia, Hb E-beta thalassaemia and delta beta-beta thalassaemia). The extent of iron overload correlated with the severity of disease. In severe thalassaemia, iron overload occurred early in life and was independent of multiple transfusions. While significant impairment of left ventricular function was present in only one of six patients studied, evidence of decreased pituitary (especially gonadotrophic) function was observed in six out of seven. Hypocalcaemia, probably due to hypoparathyroidism, was seen in one.

Iron overload in patients with haemoglobin H disease.

Serum ferritin was measured in 46 Chinese patients with Hb H disease (HbHD) and compared with 84 controls according to age group. Ferritin levels were elevated in 14 of 20 males and 20 of 26 females and the extent of the abnormality increased with age. Splenectomy did not appear to be associated with particularly high levels of serum ferritin in this disease.

Deep vein thrombosis and changes in coagulation and fibrinolysis after gynaecological operations in Chinese: the effect of oral contraceptives and malignant disease.

Of 154 Chinese patients who underwent gynaecological operations, four showed a positive 125I fibrinogen leg scan for venous thrombosis, and overall incidence of 2 . 6%. In those who were on oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10 . 5%; in those who had Wertheim hysterectomy for carcinoma of cervix, it was 6 . 7%. This confirms the rarity of post-operative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative 'fibrinolytic shutdown', represented by decreased plasminogen activator together with increased alpha 1 antitrypsin and C1- inhibitor levels, was more marked. In addition, alpha 2 macroglobulin level was lower and fell significantly after operation. In patients on oral contraceptives, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin III levels did not fall except in three of the four patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin III level might be useful diagnostic markers for postoperative venous thrombosis.

PIP: Of 154 Chinese patients who underwent gynecological operations, 4 showed a positive fibrinogen leg scan for venous thrombosis, an overall incidence of 2.6%. In those who were on (OC) oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10.5%; in those who had Wertheim hysterectomy for carcinoma for cervix, it was 6.7%. This confirms the rarity of postoperative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative fibrinolytic shutdown, represented by decreased plasminogen activator together with increased alpha 1 antitrypsin and C inhibitor levels, was more marked. In addition alpha 2 macroglobulin level was lower and fell significantly after operation. In patients on OCs, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin 3 levels did not fall except in 3 of the 4 patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin 3 level might be useful diagnostic markers for postoperative venous thrombosis.

The determination of antithrombin III by radioimmunoassay and its clinical application.

A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 microgram/dl. AT III-RIA level and biological activity (anti-Xa) was significantly correlated (r = 0.737, P less than 0.001). Plasma levels in 36 healthy males (mean +/- SD, 19.9 +/- 2.5 mg/dl) and 21 healthy females (19.1 +/- 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lower levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post-operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.

Significance of subnormal red-cell folate in thalassaemia.

Subnormal red-cell folate values were encountered in 20 of 63 thalassaemic subjects in a population with a low incidence of megaloblastosis. The abnormality was not associated with haematological changes of megaloblastosis and could not be explained on the basis of incomplete liberation of intra-erythrocytic folates, serum conjugase deficiency of vitamin B12 deficiency. Evidence is presented to indicate that it is unlikely to represent a state of subclinical folate deficiency. The exact cause of the abnormality is unknown.