Thomas G. Osborn

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus

Thrombotic microangiopathic hemolytic anemia (TMHA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and kidney involvement. It presents as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TMHA has been considered to occur only rarely in systemic lupus erythematosus (SLE). However, there has been an increase in the reporting of this association in recent years, and autopsy studies have suggested that TMHA may be underdiagnosed in SLE because of the similarity in symptoms. We report four patients with SLE-related TMHA and describe 24 more patients from a literature review. All patients were women, 50% had active SLE, 89% presented as TTP, and 11% presented as HUS. Those patients with active SLE had low complement levels. Antiphospholipid antibodies or lupus anticoagulant were positive in 5 of 8 cases. Patients treated with plasma infusions or plasmapheresis had a lower mortality rate at 25% compared with 57% mortality in patients who were not treated with plasma infusions or plasmapheresis. It is suggested that TMHA should be considered in any SLE patient presenting with neurological symptoms or renal failure associated with fever, hemolytic anemia, and thrombocytopenia. Early recognition and appropriate therapy with plasmapheresis may improve prognosis.

Heart disease in systemic sclerosis

Primary cardiovascular manifestations of SSc include pericardial disease, myocardial disease, conduction abnormalities, and cardiac arrhythmias. Significant cardiac abnormalities are present in more than half of SSc patients at autopsy. As the frequency of subclinical cardiac involvement is now appreciated and noninvasive cardiac diagnostic modalities continue to improve, the ability to detect early asymptomatic involvement in SSc has improved. Two-dimensional echocardiography, radionucleotide imaging, and ambulatory ECG allow recurrent serial testing with virtually no morbidity. The current treatment of cardiac involvement in SSc is emperic and primarily directed at symptomatology. Large prospective randomized trials are needed to determine if preventive therapy is effective. With the advent of new immunological and cardiotropic agents and a better understanding of the primary disease process, our ability to alter the pathogenesis and final outcome of cardiac involvement in SSc should improve.

Parvovirus infection mimicking systemiclupus erythematosus

There are striking similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE): both may present with malar rash, fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 infection mimicking SLE and review 10 other reported cases, all of whom were women. The similarity to a typical SLE presentation was indeed striking: most patients presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, HPV-B19 infection seemed to exacerbate SLE rather then resemble it, and differentiation was difficult. Nearly all patients improved within several weeks. However, a few patients had symptoms and laboratory abnormalities lasting more than 6 months. The possibility of HPV-B19 infection should be entertained in patients presenting with SLE-like features.

Autoantibody studies in juvenile rheumatoid arthritis

Early studies showed few immunologic abnormalities in juvenile rheumatoid arthritis (JRA) patients. There were no specific laboratory markers useful for diagnosis and assessment of the course of disease in JRA. Previous work showed an association of antinuclear antibodies (ANA) with early-onset pauciarticular disease and iridocyclitis. Similarly, the presence of 19S immunoglobulin (Ig) M rheumatoid factors (RF) was associated with late-onset polyarticular disease in girls. More recent studies have detected many unique autoantibodies. Newer assays show 19S IgM RF in up to 35% of JRA patients, although still mainly in girls with late-onset polyarticular disease. Hidden 19S IgM RF can be shown in up to 75% of JRA patients using different procedures, primarily in those with active polyarticular-or pauciarticular-onset disease. Immune complexes have been detected in JRA patients by means of different techniques; their presence usually correlates with active disease. Studies on a specific ANA in JRA have shown no common extractable nuclear antigen, but antihistone antibodies have been found in up to 75% of cases, again mainly in those with pauciarticular onset and iritis. Finally, a variety of unusual immunologic proteins have also been detected, including anti-ocular, anti-cellular, anti-cardiolipin, anti-perinuclear factor, and anti-collagen antibodies. This review evaluates the significance of these antibodies that can now be found in JRA.

Quantification of ventricular remodeling in the tight-skin mouse cardiomyopathy with acoustic microscopy

To determine the role of ultrasonic tissue characterization for the detection of changes in myocardial architecture associated with cardiomyopathy, acoustic microscopy was performed on the hearts of 4- to 6-month-old tight-skin mice [TSK/+, C57-B10.D2 (58B)/SN strain], a model of cardiomyopathy characterized by diffuse interstitial fibrosis. Ultrasonic backscatter was measured from excised segments of left ventricular free walls of five TSK mice and five sex- and age-matched normal controls with a 50 MHz broad band focused piezoelectric transducer operated in a saline-filled water tank at room temperature. Forty-nine radio frequency (RF) lines were digitized from each specimen at 2 ns/sample. Power spectral analysis of RF data was performed and mean integrated backscatter (IB) computed. The TSK group demonstrated greater IB (-53.6 +/- 0.6 dB, n = 5) than did the control group (-56.6 +/- 0.7 dB, n = 5; p < 0.02). Myocardial collagen content determined by hydroxyproline assay increased by 11% in the TSK group (2.54 +/- 0.08 microgram/mg dry wt, n = 5) over that in controls (2.28 +/- 0.07 microgram/mg dry wt, n = 5; p < 0.05). A significant linear relationship was observed between myocardial hydroxyproline concentration and IB (r = 0.74; p < 0.02). Thus, ultrasonic tissue characterization permits sensitive detection of modest changes in the extent of interstitial fibrosis that accompany tissue remodeling in the early stages of cardiomyopathy.

Autoantibodies in juvenile arthritis

Sera from 104 children with JA with different onset-types of disease were evaluated for 19S IgM RF by the LFT , hidden 19S IgM RF by the hemolytic assay, ANA by HEp-2 cell substrate, and levels of IC by the C1qSPA . Their relationship to active disease was determined. Classical 19S IgM RF were detected by the LFT in only seven patients. All were late-onset polyarticular females. Hidden 19S IgM RF were detected by the hemolytic assay in the separated IgM-containing fraction in 55 patients of all onset-types. Clinical activity correlated with the presence of hidden 19S IgM RF in 82% of cases. ANA, using the HEp-2 cell substrate, were found in 61 patients, the majority showing a speckled, immunofluorescent pattern. ANA were noted in all RF positive patients and in nine of 10 patients with iridocyclitis. IC were found in 39 patients, and correlation with clinical activity occurred in 54% of cases. A search for positive associations among the four parameters showed no statistically significant correlations except for the concordance of ANA positivity in all seven RF positive patients. The presence of hidden RF correlated more closely with disease activity (P less than 0.001) than did that of ANA or IC. The significance of these data and previous studies remains to be determined. We have demonstrated that in the average JA population 7% have 19S IgM RF and about 60% have hidden RF, ANA, or elevated levels of IC. The present findings of 98 of 104 patients with at least one of the abnormal immunoproteins , the association of ANA in patients with iridocyclitis or with RF positivity, of hidden RF with disease activity, and the presence of 19S IgM RF in isolated IC suggest a possible immunologic etiology for JA.