Epidermolysis bullosa acquisita occurring in association with systemic lupus erythematosus.

A 77-year-old retired male physician with a 6-year history of systemic lupus erythematosus (SLE) developed a mechanobullous eruption, the features of which were clinically and immunopathologically consistent with a diagnosis of 'classical' epidermolysis bullosa acquisita (EBA). As EBA shares immunopathological findings with a number of cases reported as the 'bullous eruption of SLE', the clinical findings commonly recognized as 'classical EBA' may, in patients with SLE, represent a specific subset of the bullous eruption of SLE rather than a separate diagnostic entity. There are few reports in the literature describing classical EBA in patients with SLE. Findings in this patient add further support to the suggestion that EBA occurring in association with SLE, represents a subset of the bullous eruption of SLE, the clinical features of which may be modified by genetic susceptibility or disease activity.

Persistent nephrogenic diabetes insipidus, tubular proteinuria, aminoaciduria, and parathyroid hormone resistance following longterm lithium administration.

We report a patient who developed persistent nephrogenic diabetes insipidus associated with renal tubular acidosis, renal resistance to parathyroid hormone, aminoaciduria and proximal tubule pattern proteinuria in the presence of a reduced glomerular filtration rate (19-24 ml/min). A review of the previous reports of persistent nephrogenic diabetes insipidus revealed that in all patients the glomerular filtration rate had been less than 60 ml/min at presentation. Chronic renal failure may therefore predispose to the development of persistent nephrogenic diabetes insipidus in patients receiving lithium.

Hypothesis: symmetrical cutaneous lymphoma.

Patients with malignant lymphoma may have cutaneous and subcutaneous involvement that exhibits a striking symmetry about the coronal axis. The symmetry of these lesions may be caused by site-specific migration from the circulation, preferential proliferation by lymphocytes of the neoplastic clones at defined anatomical sites, or both mechanisms. Similar behaviour by benign lymphocytes may explain the symmetry and selective anatomical distribution of lesions in other skin diseases.

Bleeding colonic varices controlled by propranolol.

A 64-year-old man with hepatic cirrhosis developed severe haemorrhage from oesophageal varices. He underwent a course of sclerotherapy injections which successfully obliterated the oesophageal varices and prevented further oesophageal bleeding. He later developed serious bleeding from a site in the region of the ascending colon; angiography and radionuclide imaging suggested that varices were present in that region. Therapy with oral propranolol was effective in preventing any recurrence of gastrointestinal bleeding.

The defect of lymphocyte locomotion in chronic lymphocytic leukaemia: studies of polarization and growth-dependent locomotion.

This paper reports a study of the locomotor behaviour of the lymphocytes from 17 patients with chronic lymphocytic leukaemia (CLL). The cells were studied both immediately after separation from blood and after culture for 24 to 48 h with a range of growth activators. Cells direct from blood were tested for polarization in fetal calf serum (FCS 20%), phorbol myristate acetate (PMA 10(-7)M) and colchicine (10(-5)M). The polarization of lymphocytes from CLL patients with high white cell (WBC) counts (greater than 10 X 10(9)/litre) was very poor in FCS and PMA, though the cells from about half of these patients responded well to colchicine. The response of cells from patients with low white cell counts was the same as that of controls. The growth activators, PHA (1 micrograms/ml), anti-CD3 antibody (OKT3 2.5 ng/ml), Cowan strain Staphylococcus aureus (SAC; 1.5 X 10(7)/ml) and PMA (10(-8)M) induced an increase in the proportion of locomotor lymphocytes from controls and from CLL patients with low white cell counts during 24 h of culture. Cells from patients with high white cell counts showed very little increase in locomotor forms in any activator including PMA and the B cell mitogen SAC. This defect was seen in both polarization assays and collagen gel invasion assays. The findings suggest that CLL lymphocytes have a defect of locomotion demonstrable at two levels: (a) the cells fail to respond by polarizing immediately upon stimulation; colchicine treatment reverses this defect in some cases; (b) they also fail to acquire locomotor capacity during culture with activators of growth.

Breast cancer, chronic lymphocytic leukaemia and mucormycosis.

Prolonged survival following diagnosis of lipid-rich carcinoma of breast is unusual. We report on a patient in whom lipid-rich carcinoma of one breast, invasive ductal carcinoma of the other breast and chronic lymphocytic leukaemia were diagnosed simultaneously; she survived 14 years without breast tumour recurrence and died with atypical mucormycosis.

Failure of conventional chemotherapy in aggressive lymphomas.

Between 1975 and 1982 in 2 centres in Glasgow, 53 previously untreated patients with aggressive non-Hodgkin's lymphomas received chemotherapy consisting of one of the following regimens-CVP, MOPP, CHOP or BACOP. Twenty nine patients (55%) entered complete remission (CR), 20 (38%) had partial remission (PR) and 4 (7%) had progressive disease (PD). Of the 29 patients in CR, 9 have relapsed and died, 5 died of infection, 4 died of non-malignant causes, and 11 (21%) remain alive and disease free. The median survival for the CR group is 40 months. All of the patients in the PR and PD group are dead, median survival 11 months. These chemotherapy regimens will cure only the minority of patients with aggressive lymphomas and the use of more intensive regimens is indicated.

The incidence, clonal origin and secretory nature of serum paraproteins in chronic lymphocytic leukaemia.

Immuno-isoelectric focusing (IIEF) showed a 61% incidence of serum paraproteinaemia in 56 patients with chronic lymphocytic leukaemia (CLL). A strong correlation between the serum paraprotein heavy chain isotypes and those of the cytoplasmic heavy chain immunoglobulins was observed with no discrepancy noted in light chain expression. Density gradient ultracentrifugation analysis of selected sera containing monoclonal IgM showed that the IgM paraproteins were mostly 19S, secretory IgM but one patient was found to have both 19S and 8S monoclonal IgM. When the cellular origin of the IgM and IgD paraproteins found in one patient was investigated, both paraproteins were found to share the same idiotype and originate from the neoplastic clone. These findings confirm the view that there is an incomplete maturation block in chronic lymphocytic leukaemia and that in vivo secretion of paraproteins by the neoplastic cells is a relatively common occurrence.

The incidence and possible relevance of Bence-Jones protein in the sera of patients with multiple myeloma.

We present results showing that the detectable incidence of Bence-Jones protein in the sera of patients with multiple myeloma is equivalent to the highest detectable incidence of Bence-Jones protein in highly concentrated urine when tested by immuno-isoelectric focusing. In a series of 25 multiple myeloma patients, immuno-isoelectric focusing showed the incidence of Bence-Jones proteinemia to be 68% compared with a detectable incidence of Bence-Jones proteinuria of 32-64% by immunoelectrophoresis and immuno-isoelectric focusing depending upon the urine concentration factor. In view of the variability of factors governing urinary Bence-Jones protein levels, such as renal catabolism, reabsorption and losses during concentration, we suggest that monitoring of serum Bence-Jones protein by immuno-isoelectric focusing should be carried out in conjunction with measurements of urinary Bence-Jones protein in multiple myeloma.

Pseudohyperkalaemia.

When the serum potassium concentration is raised and there is no clinical or electrocardiographic evidence of hyperkalaemia pseudohyperkalaemia must be considered.

Serum paraproteins in chronic lymphocytic leukaemia.

The presence of paraproteins in the sera of 10 patients with chronic lymphocytic leukaemia (CLL) was investigated using immunoisoelectric focusing. Monoclonal immunoglobulins were found in nine of these 10 sera. Five sera contained a single monoclonal IgM paraprotein, one serum contained a single monoclonal IgG paraprotein, while three sera contained more than one monoclonal paraprotein--namely, IgM + IgD, IgM + IgG, and IgM + IgD + IgG. The results indicate that the malignant B cells of CLL may be at a later stage of differentiation than previously assumed and serum monoclonal immunoglobulin could be of value as a tumour marker.

Meningeal relapse in Ph1-positive acute lymphoblastic and lymphoid blast crisis of chronic granulocytic leukemia. Is CNS-prophylaxis indicated?

Two cases of Ph1-positive acute lymphoblastic leukemia (ALL) and one case of lymphoid blast crisis (LyBc) of chronic granulocytic leukemia (CGL) treated with standard chemotherapy for ALL are presented. Hematologic remissions lasting 6, 12, and 15 months were achieved in all cases. Meningeal relapse occurred in all three, terminating remission in two cases and occurring immediately after systemic relapse in the third. No CNS-prophylaxis was given to the patient who relapsed at six months. Methotrexate (MTX) alone or combined with cranial irradiation formed the prophylaxis given in the other cases. Experience of these patients together with an analysis of reported cases of Ph1 ALL and CGL-LyBc suggests CNS-prophylaxis may prolong first remission. A large scale trial of this appears indicated.

Acute myelogenous leukaemia following cytotoxic therapy: five cases and a review.

Acute myelogenous leukaemia (AML) following cytotoxic chemotherapy has been reported increasingly. Five new cases are presented including the first described following treatment for immune thrombocytopaenia. A review of the literature has revealed 226 case reports of treatment-linked AML with sufficient detail to permit further study. Of the total of 231 patients, 76 (33 per cent) followed Hodgkin's disease, 59 (25.5 per cent) multiple myeloma, 22 (9.5 per cent) non-Hodgkin's lymphoma, 32 (14 per cent) other solid tumours and 42 (18 per cent) non-malignant diseases. The time interval from the start of chemotherapy to the diagnosis of AML was similar in all disease groups whether the patients had received radiotherapy or not. Differences emerged when the duration of exposure to chemotherapy was analysed in the individual disease groups; exposure was shorter in those patients treated for Hodgkin's disease and solid tumours than with the others suggesting that the pattern of administration of chemotherapy may be important. The effects of radiotherapy in addition to chemotherapy could not be defined precisely, but the study highlights the particular risk that appears to arise from alkylating agents, and the need to define optimal methods of administration of chemotherapy with minimal risk of inducing leukaemia.