Lupus retinopathy

In a prospective study of 550 patients with systemic lupus erythematosus (SLE), 41 were found to have retinopathy. Lupus retinopathy in the majority of cases consisted of a microangiopathy, with an excellent prognosis for vision. Five patients developed other complications that resulted in loss of visual acuity. Lupus retinopathy was associated with active SLE in 88% of patients and with lupus cerebritis in 73% of cases. Retinopathy in SLE was a marker of poor prognosis for survival.     

Lymphoid interstitial pneumonia: clinical features, associations and prognosis.

Lymphoid interstitial pneumonia (LIP) is rare and its clinical course incompletely described. The aim of this study was to examine the clinical features, associations and prognosis of surgical lung biopsy-proven LIP. The study group consisted of 15 subjects encountered over a 14-yr period. The majority of subjects were females (n = 11) and the mean age was 47 yrs (range 17-78 yrs). Underlying systemic immune disorders were frequent, including Sj?gren's syndrome (n = 8), rheumatoid arthritis, systemic lupus erythematosus, polymyositis, common variable immunodeficiency and dysproteinaemia. Only three patients were classified as "idiopathic". Presenting symptoms were dominated by dyspnoea and cough. Restrictive physiology, reduced diffusion capacity (62.5+/-18.4% predicted) and bronchoalveolar lavage lymphocytosis (30.5+/-29.1% pred) were noted. Thirteen patients received corticosteroid therapy. Of the nine whose response could be assessed, four showed clinical improvement and four were stable. Overall, median survival was 11.5 yrs. Of the seven patients who died, respiratory problems were the primary cause of death in three. Conversion to lymphoma was not identified. In conclusion, histopathological lymphoid interstitial pneumonia is commonly associated with immune system dysregulation, with idiopathic lymphoid interstitial pneumonia being extremely rare. Clinical stability or improvement with corticosteroids can be expected; however, survival remains impaired.     

Lupus anticoagulants in systemic lupus erythematosus: prevalence and clinical associations.

The prevalence of lupus anticoagulant (LAC) and its relation with reported clinical associations has been determined in 55 patients with systemic lupus erythematosus (SLE) from northern India who were studied prospectively. Kaolin clotting time was used to screen for LAC, which was detected in seven (13%) of the patients. Significant associations were found between LAC and thrombotic events, onset of disease at an early age, and disease of shorter duration. No statistically significant association could be found between LAC and recurrent abortions, pulmonary hypertension, thrombocytopenia, and neurological manifestations. It is concluded that LAC is a useful marker for a subset of patients with SLE at risk of thromboembolic events.     

Lupus: improving long-term prognosis

Over recent decades short- and medium-term survival has greatly improved in patients affected with systemic lupus erythematosus, but long-term prognosis still remains poor mainly due to complications of the disease and/or its treatment. To improve long-term prognosis in systemic lupus erythematosus, we should try to adopt, early in the disease course, strategies that can contribute to reducing long-term complications, including screening for and prophylaxis against infections, control of risk factors for atherosclerosis, and cancer surveillance. However, in patients with systemic lupus erythematosus all these preventive strategies are often not sufficient. Indeed, two important systemic lupus erythematosus-related factors play a relevant role in all these complications: severe disease manifestations, such as glomerulonephritis and central nervous system involvement, and corticosteroid and cyclophosphamide use. Therefore, to prevent long-term complications, we should try to control disease activity and severity using the lowest effective dosage of these drugs. Moreover, strategies directed at preventing clinical manifestations in asymptomatic antinuclear antibody-positive individuals or in antiphospholipid antibody-positive systemic lupus erythematosus patients, as well as at preventing severe manifestations in patients with mild systemic lupus erythematosus at the time of the diagnosis should be considered.     

Childhood-onset Systemic Lupus Erythematosus: clinical presentation and prognosis in 31 patients.

OBJECTIVE: To determine the clinical features at onset, the disease course, and prognostic factors in children with SLE. METHODS: The medical records of 31 patients with childhood-onset SLE were reviewed. Signs and symptoms at onset and during the course of the disease were documented as well as survival and SLICC/ACR damage index. The disease course was compared to 135 consecutive adult-onset SLE patients. RESULTS: Childhood-onset SLE most frequently presented with fatigue, arthritis, fever, weight loss, and malar rash. During follow-up, the frequency of the presence of malar rash, anemia, leukocytopenia, and anti-dsDNA antibodies was significantly higher in childhood-onset than in adult-onset patients. Mean SLICC/ACR damage index was 2.6 after 4.7 years of follow-up. The presence of arthritis, anemia, and seizures at the onset of disease resulted in a 2.6 to 3.9 times higher chance of a severe disease course. CONCLUSION: Patients with childhood-onset SLE suffer from substantial morbidity. Arthritis, anemia, and seizures at onset may be indicators of poor prognosis.     

Patterns and prognosis ofClostridium difficile colitis

The incidence of Clostridium difficile colitis has increased during recent years, presumably because of liberal use of broad-spectrum antibiotic regimens. METHODS: A retrospective review to determine patterns of C. difficile colitis development, morbidity, and treatment results was undertaken. During an 18-month period, 90 patients were diagnosed with C. difficile colitis by fecal toxin assays. Patient demographics, symptoms, previously administered antibiotic regimens, diagnostic evaluations, treatment modalities, morbidity, and mortality were identified, entered into a computer data base, and analyzed. RESULTS: The mean age was 58 years; males outnumbered females 1.21. Among 90 patients, 41 (46 percent) developed C. difficile colitis after surgical procedures. Eighty (89 percent) patients received antibiotic therapy before developing C. difficile colitis: 35 (44 percent) for documented infections and 45 (56 percent) as empiric or prophylactic therapy. Cephalosporins, penicillins, quinolones, vancomycin, and aminoglycosides were the most frequently administered antibiotic classes prior to C. difficile colitis diagnosis. Ten (11 percent) patients developed C. difficile colitis without previous antibiotic therapy. Eighty-two (91 percent) patients presented with diarrhea, while eight (9 percent) had fever only. Primary C. difficile colitis treatment for both groups included vancomycin (66 percent), metronidazole (24 percent), or both drugs (10 percent). Ten (11 percent) patients received no treatment. No patient developed toxic colitis or megacolon. Colonoscopy was performed in four (4 percent) patients; pseudomembranes were identified in one (25 percent) patient. There was one C. difficile colitis recurrence after treatment, but no C. difficile colitis-associated morbidity. Mortality (14 patients, 16 percent) was not related to C. difficile colitis, but to underlying illness. No difference in patient age, sex, previous antibiotic administration, serum albumin, total days hospitalized, duration of C. difficile colitis antibiotic therapy,C. difficile colitis treatment regimens, or mortality was identified between nonsurgical and surgical patients. The white blood cell count was significantly lower in the nonsurgical group however.Clostridium difficile colitis developed most commonly after antibiotic administration with symptoms of diarrhea, but did occur without previous antibiotic administration or diarrhea. CONCLUSION: Despite the clinical setting,C. difficile colitis had no associated morbidity and treatment was highly effective. Mortality was related to underlying medical illness, not C. difficile colitis.Read at the meeting of The American Society of Colon and Rectal Surgery, Chicago, Illinois, May 2 to 7, 1993.     

Ischemic colitis: Patterns and prognosis

We identified 47 patients with nonocclusive ischemia of the large intestine over a seven-year period. The mean age at presentation was 56.2 years, with a 221 male predominance. Associated medical illnesses were diabetes (17 percent), renal failure (5 percent), and hematologie disorders (5 percent). Six patients developed ischemic colitis after aortic surgery. The mean delay in diagnosis was 1.8 days (range, three hours to 23 days). The right colon was involved in 21 patients (46 percent). Overall, 15 of 16 patients were successfully treated non-operatively with bowel rest and antibiotics; one patient who was managed nonoperatively died. Among the 31 requiring intestinal resection, enteric continuity was reestablished in 14. Second-look laparotomy in eight patients revealed further ischemia in two (20 percent). Mortality in the operative group was 29 percent (9 of 31). No patient has developed recurrent ischemia (mean follow-up, 5.3 years). Ischemic colitis often occurs without an obvious predisposing event, may involve all segments of the large intestine, and frequently requires surgery. While its course may be self-limited, elderly and diabetic patients, as well as those developing ischemia following aortic surgery or hypotension, continue to have a poor prognosis.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies.

Lymphocytotoxic antibodies (LCTAB) were sought in sera of patients with rheumatic diseases and in family members. Patients with SLE and cutaneous necrotizing venulitis and family members of JRA patients had an increased frequency of LCTAB; JRA patients and family members of SLE patients did not. The only association between LCTAB and the HLA phenotype of persons with LCTAB was a decreased frequency of LCTAB in individuals with HLA-B27.     

A Sensitive Test Demonstrating Lupus Anticoagulant and its Behavioural Patterns

The kaolin clotting time of platelet poor plasma was used as a sensitive test for detecting the lupus anticoagulant in mixtures of normal and patients' plasmas. Platelets were found to decrease the anticoagulant effect of a typical lupus inhibitor. Thus, high sensitivity in this test system was achieved by ensuring low platelet concentrations and omitting platelet lipid substitute. In 17 patients with disseminated lupus erythematosus (DLE), 12 had detectable inhibitor by this method, more than would be detected with routine coagulation tests. Mixing patterns were of four distinct types, representing three different modes of anticoagulant behaviour. The pattern (type 3) of plasma mixtures giving longer kaolin clotting times than the individual components could be reproduced in vitro by adding trace amounts of crude thrombin or platelet fragments to a more typical lupus anticoagulant-containing plasma; formation of such a mixing pattern by the plasma of a patient with DLE may therefore indicate activation of the coagulation pathway. Six patients with idopathic thrombocytopenic purpura (ITP) had no detectable inhibitor indicating that anti-platelet antibodies behave differently from the lupus anticoagulant.     

Lupus retinopathy associated with a high IFN-alpha level in the cerebrospinal fluid

An 18-year-old woman who presented with photosensitivity, butterfly rash and acute visual disturbance was diagnosed as SLE with retinopathy. The level of IFN-alpha in the cerebrospinal fluid (CSF) was markedly elevated. Her visual acuity recovered with high-dose prednisolone therapy. IFN-alpha in the CSF also reduced to within the normal range. The mechanism causing lupus retinopathy is not clearly understood. Although the association between lupus retinopathy and a high level of IFN-alpha has not been reported, the injection of IFN-alpha is known to frequently cause retinopathy in hepatitis patients. We discuss the possibility of IFN-alpha causing retinopathy in SLE patients.     

Lupus pernio.

Thirty-five patients with lupus pernio have been observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinical and radiological features. It predominates in women, and particularly in West Indians. The chronic persistent violaceous skin lesions have a predilection for the nose, cheeks, lips, eyelids, ears and fingers, ranging from a few nodules under the tip of the nose to exuberant plaques spreading across the nose and both cheeks. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It is distinguished from lupus vulgaris and lupus erythematosus by clinical features, histology and radiology.     

Lupus anticoagulant.

Acquired antibodies to phospholipids form a heterogeneous group, which may be detected in vitro by the inhibition of phospholipid dependent tests of coagulation (lupus anticoagulant) and also by immunological assays, such that a combined approach is required for their reliable detection. While initially described in sufferers from systemic lupus erythematosus, these antibodies are increasingly recognised in a broad spectrum of disease, most importantly in relation to thromboembolism and recurrent fetal loss; occasionally they may also be found in otherwise healthy individuals. The mechanisms underlying the prethrombotic state associated with these antibodies have not been defined, although interference with the natural anticoagulant systems seems possible. Identification of antiphospholipid in subjects with spontaneous thromboembolism may influence therapeutic decisions, while their presence in women with recurrent fetal loss has lead to attempts to alter the outcome of further pregnancies with anticoagulant and immunosuppressive regimens, however the optimum management has not yet been determined. The recognition of these antibodies and their clinical associations is therefore highly relevant to clinical and laboratory haematology.     

Lupus anticoagulants, thrombosis and the protein C system.

Although lupus anticoagulants (LAs) are immunoglobulins that inhibit procoagulant reactions in vitro, these molecules are associated with thrombosis in vivo. We and others have hypothesized that this may be due to selective targeting of the activated protein C (APC) anticoagulant pathway. Populations of antibodies that interact with protein C or protein S in ways that inhibit their activity are obvious candidates for such pathological molecules. However, it is less clear how populations that appear to bind to membrane surfaces might target the APC anticoagulant complex selectively. Studies now show that the membrane requirements of the APC anticoagulant complex are significantly different from those of the procoagulant reactions. The most dramatic difference is the requirement for the presence of phosphatidylethanolamine (PE) in the membrane for optimal APC function. The inhibitory activity of at least some LAs is enhanced by the presence of PE, but the anti-APC activity is enhanced even more, resulting in the plasma from these patients clotting faster than normal when APC is present. Structure-function studies have been undertaken to understand the PE dependence of this reaction better. Chimeric proteins in which all or part of the Gla domain of protein C has been replaced by the homologous region of prothrombin have been prepared. Unexpectedly, the PE dependence resides primarily in the C-terminal half of the Gla domain. Using liposomes of various composition, we found both the presence of the PE head group and unsaturation of the fatty acid chains are required for optimal inactivation of factor Va. It is hoped that a better understanding of the biochemistry of these reactions, combined with the use of the chimeric proteins described, will permit us to design better assays for the identification of pathologic LAs.     

Kawasaki disease. Epidemiology, late prognosis, and therapy.

Kawasaki disease is an immunologically mediated diffuse vasculitis of childhood of unknown etiology. While most of the clinical features--including diffuse mucosal inflammation, indurative edema, rash, and lymphadenopathy--are self-limiting, coronary artery aneurysms and the possibility of thrombotic occlusion occurs in up to 20% of children. The epidemiologic and clinical features of this disease suggest an infectious etiology; however, a specific organism has not been consistently identified. An abnormal immune response to this as yet to be defined organism plays a critical role in the progression of this disease. The morbidity and mortality of this disease are related primarily to the potential cardiovascular complications. The natural history of the coronary artery aneurysms is that most lesions regress with time. Factors leading to a higher probability of regression include age less than 1 year, female sex, fusiform aneurysm, and maximum diameter less than 4 mm. Current recommendations for therapy include aspirin and IVIG. The range of dosages regimens for each medication are discussed in the text.