Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

Late onset systemic lupus erythematosus.

This study describes the clinical and laboratory features and the natural history of 31 patients with late onset (in the sixth decade or later) systemic lupus erythematosus (SLE). Patients with late onset SLE constitute a distinct subset of the general lupus population that accounts for approximately 12 per cent of the cases. Advanced age modifies the expression of SLE in terms of clinical presentation (pleuritis and/or pericarditis are the most common presenting manifestations) and pattern of organ involvement (pulmonary abnormalities are more common, whereas lymphadenopathy, Raynaud's phenomenon, neuropsychiatric disease, alopecia and skin rash are less common). Because SLE is not usually considered to be a disease that affects the elderly, and because the pattern of SLE in the older age group may differ substantially from the seen in younger patients, there is often a delay in diagnosis (median of 10 months, with a delay of over one year in 32 per cent of patients). In light of the high incidence of steroid complications in older patients (40 per cent in our series), and because these patients with SLE have a relatively good prognosis (five year survival of 92.3 per cent; nine year survival of 83.1 per cent), therapy should be more conservative in late onset SLE.     

Systemic lupus erythematosus. Morphologic correlations with immunologic and clinical data at the time of biopsy.

The findings in 77 biopsy specimens from 59 patients with systemic lupus erythematosus were compared with the immunologic data gathered at the time of biopsy. The biopsy specimens were classified by a number of morphologic parameters in an attempt to see which classification offered the best correlation with the immunologic data. These parameters included: (1) over-all amount of deposits of immunofluorescence; (2) distribution of deposits on immunofluorescence; (3) amount and distribution of glomerular proliferative lesions; (4) classification of Baldwin et al. The best correlations were obtained with the over-all amount of deposits or with a classification based upon their distribution. Correlations with glomerular proliferative lesions or with the standard classification based upon these proliferative lesions were poorer.Excellent correlations were obtained between increasing morphologic lesions and increasing levels of DNA-binding, and decreasing concentrations of the third component of complement (C3). Somewhat broader and poorer correlations were also found with increasing antinuclear antibody and lupus erythematosus cell positivity, decreasing levels of the fourth component of complement (C4) and diminished titers of thymic hormone. Immune complexes, as detected by the polyethylene glycol (PEG) method, were present in the vast majority of untreated patients with renal immune deposits, but treatment suppressed PEG positivity in the majority of such patients. Rheumatoid factor and cryoglobulins showed an interesting relationship to one another, in that rheumatoid factor was confined to the patients with milder lesions and cryoglobulins largely to the patients with more severe lesions; no patient in our series was positive for both simultaneously. There was no correlation between the levels of immunoglobulins or of T and B lymphocytes, and the severity of morphologic lesions, although there were significant differences in these parameters between treated and untreated patients.Excellent correlations were also found with the following clinical parameters: serum creatinine and urea, level of hematuria, level of proteinuria and presence of hypertension. These tended to substantiate the validity of the correlations with the immunologic data. Results for creatinine clearance were more erratic.     

Immunologic events preceding clinical exacerbation of systemic lupus erythematosus

A patient with diffuse glomerulonephritis due to systemic lupus erythematosus is described. Serial urinalyses and special immunologic determinations were performed as he responded to treatment of his first attack of systemic lupus erythematosus. The sequence of immunologic events preceding the onset of his second attack of lupus nephritis are recorded. Falling levels of total serum complement (CH₅₀) and of the first component of complement (C1q), rising levels of antibody to double and single stranded deoxyribonucleic acid (DNA) and finally circulating protein complexes that precipitate C1q in vitro developed months before clinical evidence of exacerbation of his extra renal or renal disease. Abnormalities of L-chain protein metabolism provided a particularly early guide to exacerbation of the disease. The use of this group of laboratory determinations to anticipate exacerbations of the disease and to guide therapy is discussed.     

Impaired cell-mediated immunity in systemic lupus erythematosus (SLE). A controlled study of 23 untreated patients.

Cell-mediated immunity was evaluated in 23 patients with systemic lupus erythematosus (SLE) prior to therapy and in 23 control subjects. The patients with SLE who had moderate to severe disease activity had significantly fewer positive delayed skin tests to streptokinase-streptodornase (SK-SD) and Candida than the control subjects, and a higher frequency of anergy than either the control subjects or the patients with mild SLE. Significant impairment of lymphocyte transformation to all common antigens tested was found in patients with SLE as compared to both normal subjects and control subjects with disease. Phytohemagglutinin response was reduced in patients with SLE as compared to normal subjects but not to the control subjects with disease. Lymphocyte transformation responses to SK-SD and Candida were also significantly lower in patients with moderate to severe SLE as compared to patients with mildly active SLE. Primary immune response to keyhole limpet hemocyanin (KLH) was impaired in patients with SLE as measured by lymphocyte transformation and total KLH antibody, but not 2-mercaptoethanol resistant antibody. The data indicate defective T-cell function in SLE, and suggest that the impairment relates in part to disease activity.     

Paradoxical glucose-induced hyperkalemia. Combined aldosterone-insulin deficiency.

Severe hyperkalemia associated with spontaneous hyperglycemia as well as with the intravenous infusions of glucose occurred in an insulin-requiring diabetic patient in the absence of potassium administration, the use of diuretics which inhibit urinary potassium excretion or acidemia. Metabolic balance studies revealed, in addition to diabets, the presence of isolated aldosterone deficiency of the hyporeninemic type. Intravenous glucose infusions (0.5 g/kg body weight) produced significant hyperkalemia but desoxycortisone acetate (DOCA) therapy (10 mg/day) prevented the glucose-induced hyperkalemia. In this patient, the serum potassium concentration increases after the intravenous infusions of glucose because there is insufficient aldosterone and insulin to reverse the transfer of potassium to the extracellular fluid which normally occurs after hypertonic infusions of glucose. Although DOCA replacement modifies the distribution of potassium in the extracellular fluid and blunts the hyperkalemic effect of intravenous infusions of glucose, a rise in the insulin level is required for the usual hypokalemic response to intravenously administered glucose. These studies illustrate the risk of raising blood glucose levels in patients with combined aldosterone and insulin deficiency and the tendency towards hyperkalemia in diabetic patients under certain clinical conditions.     

Estimating prognosis in systemic lupus erythematosus

Knowledge of prognosis is critical for rational choice of therapy. Systemic lupus erythematosus, with its broad clinical spectrum, presents an example of the problem of prognostication for the individual patient. The life table method can provide prognostic information. It need not be limited to estimation of survivorship, and its utility can be multiplied by a computer databank. Analysis of prognosis for different groups of patients, from different events in their course, over different time periods, and to different end points can then be performed. Using this technic, specific clinical variables in systemic lupus erythematosus were assessed for their effect upon particular outcomes. Clinical variables representing functional organ impairment were found to carry a worse prognosis than the popular serologic indicators. New abnormalities were found to occur less frequently in later years of the disease. Different subpopulations of patients have strikingly different expectations, and these differences carry important therapeutic implications.     

Discoid lupus erythematosus with macroglobulinemia. Correlations between autoimmunity and B cell malignancy with hyperimmunoglobulinemia

A 44 year old woman presented with discoid lupus erythematosus and then chronic lymphocytic leukemia of the B cell type with macroglobulinemia developed. Immunologic studies revealed suppressed thymus-dependent cell function, increased bone marrow-dependent cells of the immunoglobulin M (IgM) class and increased null cells.The pathogenesis and relation of lupus erythematosus to B cell malignancy with hyperimmunoglobulinemia are discussed.     

Autoimmune hemolytic anemia and periodic pure red cell aplasia in systemic lupus erythematosus

A patient with systemic lupus erythematosus and autoimmune hemolytic anemia complicated by periodic episodes of red cell hypoplasia is described. Using a plasma clot culture system a serum inhibitor of erythropoiesis was detected. In addition, heat eluates of the red cells of this patient were capable of impairing erythroid colony formation. The possibility that the autoantibodies of acquired autoimmune hemolytic anemia might influence the proliferation and/or maturation of erythroid progenitor cells is raised by these findings.     

Hyperchloremic metabolic acidosis after chlorine inhalation

Chlorine gas Inhalation is usually accompanied by pulmonary toxicity and hypoxemia; the associated acidemia, when present, has been attributed to lactic acidosis. This case report describes the development of hyperchloremic metabolic acidosis following accidental chlorine gas exposure. The mechanism postulated for the production of this acidosis is the absorption of hydrochloric acid following the reaction of chlorine gas with tissue water. This may be the first case of chlorine toxicity in which the mechanism of the acidosis has been determined.     

Noninvasive assessment of load reduction in patients with asymptomatic aortic regurgitation

Afterload reduction in chronic asymptomatic aortic regurgitation might retard left ventricular enlargement and hypertrophy and, consequently, delay the onset of myocardial dysfunction and the need for surgical intervention. Since afterload is best expressed as wall stress, the effect of nitroglycerin on wall stress was determined in 10 normal subjects and in eight asymptomatic subjects with aortic regurgitation and normal left ventricular and circulatory function. Peak and end-systolic wall stress were estimated using a noninvasive echocardiographic technique. At rest, despite significantly larger left ventricular dimensions in the subjects with aortic regurgitation, peak systolic wall stress in this group (134 ± 29 × 10³ dynes/cm²) was similar to that in normal subects (134 ± 26 × 10³ dynes/cm²). In contrast, end-systolic wall stress was higher in aortic regurgitation (84 ± 12 versus 59 ± 15 × 10³ dynes/cm²) (P < 0.01). Following the administration of nitroglycerin, the subjects with aortic regurgitation had larger reductions in left ventricular end-diastolic (3.5 mm) and end-systolic (3.1 mm) dimensions than did the normal subjects (0.6 and 1.1 mm, respectively), despite similar changes in blood pressure. This resulted in normalization of end-systolic wall stress and in reduction of peak systolic wall stress below normal in aortic regurgitation. We conclude that (1) nitroglycerin offers a simple and effective means of acutely reducing afterload in asymptomatic aortic regurgitation; (2) left ventricular dimensional changes after the administration of nitroglycerin are larger in subjects with aortic regurgitation than in normal subjects. Consequently, unloading therapy may be effective in protecting the left ventricle in this disorder.     

Massive spontaneous unilateral hemothorax in systemic lupus erythematosus

Described here is an unusual pulmonary complication of systemic lupus erythematosus in a 37 year old man with an 8 year history of the disease. His management and further central nervous system complications are discussed.     

Behçet's syndrome: Report of a case associated with pericardial effusion and cryoglobulinemia treated with indomethacin

A patient with Behçet's syndrome manifested by optic atrophy, purulent conjunctivitis and orogenital ulcerations presented with a high fever and pericardial effusion. A mixed cryoglobulinemia (immunoglobulin A (IgA)-immunoglobulin G (IgG)) was observed. Treatment with indomethacin resulted in rapid defervescence, resolution of the pericardial effusion and the orogenital ulcerations, and disappearance of the cryoglobulinemia. Discontinuation of indomethacin therapy was followed by a recurrence of the oral and genital ulcerations that responded promptly to the reinstitution of indomethacin treatment.     

Unusual electrocardiographic finding—Bifascicular block due to hyperkalemia

A unique case in which the patient had bifascicular block consisting of right bundle branch block and left posterior hemiblock as a result of marked hyperkalemia is presented. To our knowledge, this is the first reported case in which such unusual electrocardiographic abnormalities due to hyperkalemia were demonstrated. The electrocardiographic abnormalities produced by hyperkalemia in this case disappeared promptly by hemodialysis, as the serum potassium level returned to normal. It has been stressed that hyperkalemia should be considered as an important etiologic factor in the differential diagnosis of bundle branch block, hemiblocks and bifascicular block, particularly when these intraventricular blocks are produced suddenly.     

The essential action of propranolol in hypertension.

The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade.     

Abnormalities of delayed hypersensitivity in systemic lupus erythematosus

Abnormalities of delayed hypersensitivity were found in patients with active systemic lupus erythematosus (SLE). The following immune responses were noted in 39 patients with SLE compared to 30 normal controls: (1) delayed hypersensitivity skin test responses to purified protein derivative (PPD) and trichophyton were significantly reduced in the patients with SLE, (2) in vitro lymphocyte transformation to PPD was normal, (3) the majority of patients with SLE had circulating antibodies to native deoxyribonucleic acid (nDNA), (4) these patients did not exhibit increased skin test responses or lymphocyte transformation to nDNA. The impairment in delayed hypersensitivity to PPD and trichophyton suggests that skin testing with PPD is inadequate to screen patients with SLE for tuberculosis. Furthermore, frequent infections which occur in some patients with SLE may result in part from their impaired cellular immune responses. The dissociation between skin response and lymphocyte transformation to PPD suggests that defects in cellular immunity may be selective. The dissociation between humoral and cellular immunity to nDNA suggests that control mechanisms exerted on one or both of these responses may be defective in SLE.     

High-dose intravenous methylprednisolone pulse therapy in systemic lupus erythematosus

To determine guidelines for treatment with high-dose intravenous methylprednisolone in lupus nephritis, we prospectively assessed the response to pulse therapy in 34 patients. In 12 of them, serum creatinine decreased by at least 20 percent within two months of treatment whereas in the remaining 22 there was no such response. Patients who responded were characterized by recent deterioration in function whereas nonresponders had had a more stable antecedent course (p = 0.003). Responders also had more diffuse lesions on renal biopsy (p = 0.028), had higher levels of anti-DNA antibodies (p < 0.05), and tended to have higher tilers of immune complexes and lower total hemolytic complement.High-dose intravenous methylprednisolone therapy may lead to striking improvement in renal function in lupus nephritis, especially in the subset of patients with recent antecedent functional deterioration. This improvement was maintained in 60 percent of the patients who responded for at least six months.