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Nonlupus nephritides in patients with systemic lupus erythematosus: A comprehensive clinicopathologic study and review of the literature.
Baranowska-Daca E, Choi YJ, Barrios R, Nassar G, Suki WN, Truong LD.
Renal Pathology Laboratory, Department of Pathology, and the Renal Section, Department of Medicine, the Methodist Hospital and Baylor College of Medicine, Houston, TX. Accepted for publication May 23, 2001.
Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis. HUM PATHOL 32:1125-1135. Copyright 2001 by W.B. Saunders Company
PMID: 11679948 [PubMed - in process]
Ulcerating plantar keratoderma in association with systemic lupus erythematosus.
Grossberg EB, Scherschun L, Fivenson DP.
Department of Dermatology, Henry Ford Health System, Detroit, Michigan 48202-2608, USA.
This report highlights the finding of ulcerative plantar keratoderma in two patients with systemic lupus erythematosus (SLE). Both patients suffered from painful plantar ulcerations and fissures; in one patient there was diffuse desquamation over the entire plantar surface, while the other patient's lesions were focal and accentuated over weight-bearing surfaces. Other etiologies for keratoderma including papulosquamoua disease, contact dermatitis, tinea and primary keratodermas were excluded. Both patients were resistant to multiple topical therapies including super-potent topical corticosteroids, vitamin D analogues and retinoids, but did report moderate relief with hydrocolloid dressings applied over super-potent topical corticosteroids and pressure off-loading measures. Lupus-associated keratoderma can be recurrent and recalcitrant to treatment, often necessitating aggressive therapy and particular attention to advanced wound care methodologies. While not a specific cutaneous sign of lupus, it should be recognized as a cause for considerable morbidity.
PMID: 11678455 [PubMed - in process]
CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus.
Liu MF, Wang CR, Lin LC, Wu CR.
Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China. Mfliu@mail.ncku.edu.tw
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a structural homologue of CD28, has been reported to be an important negative regulator of autoimmune diseases. Recent studies showed that CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases, suggesting that CTLA-4 gene is probably a general susceptibility gene to autoimmune disease. The present study was conducted in Chinese to determine whether there is any association of the CTLA-4 gene polymorphism with the development of systemic lupus erythematosus (SLE). CTLA-4 gene polymorphism in promoter and exon 1 was detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 81 patients with SLE and 81 normal controls. The results showed that there were no statistically significant differences in both exon 1 and promoter gene polymorphism between SLE patients and normal controls. The preliminary study does not suggest an association of the known polymorphism in exon 1 and promoter of CTLA-4 gene with Chinese SLE. However, SLE is a very heterogeneous syndrome and CTLA-4 gene polymorphism might correlate with some specific clinical features. To exploring this possibility, subgroup analysis in more patients needs to be performed.
PMID: 11678454 [PubMed - in process]
Geographical variation in mortality from systemic lupus erythematosus in the United States.
Walsh SJ, DeChello LM.
Department of Community Medicine, School of Medicine, University of Connecticut Health Center, Farmington 06030-6325, USA. walsh@nso.uchc.edu
The aim was to identify demographic and environmental factors that affect the incidence and course of systemic lupus erythematosus (SLE) by studying geographical variation in mortality from the disease. Counts of SLE deaths during a 10-y period were determined for each of the 3111 counties in the United States. The counts were subjected to statistical techniques for detecting spatial clusters with significantly higher or lower mortality than expected. Census data were used to compare attributes of the resulting clusters. Four clusters with significantly elevated SLE mortality were identified. They were centered in Alabama, Arkansas, Louisiana and New Mexico and had 41-65% more SLE deaths than expected. Four other clusters with significantly low mortality were centered in Minnesota, Vermont, Virginia and Washington and had 32-44% fewer deaths than expected. Comparison of SLE mortality rates between the New Mexico and Vermont clusters yielded relative risks of 3.2, 3.4 and 5.9 for white, black and other race women, respectively, and of 2.1, 5.2 and 'undefined' for white, black and other race men. Census data showed that the clusters with elevated mortality had higher poverty rates and/or greater concentrations of ethnic Hispanics than those with lower mortality. SLE mortality rates show great regional variation within the United States. The variation appears to reflect, in part, geographical patterns in socioeconomic status and in the distribution of persons of Hispanic origin.
Titration emulation: a computer-assisted technique that simplifies the quantification of anti-dsDNA antibodies using the Crithidia luciliae assay.
Satoh M, Behney KM, Mizutani A, Richards HB, Hutson AD, Reeves WH.
Department of Medicine, University of Florida, Gainesville 32610-0221, USA. satohm@medicine.ulf.edu
Titers of anti-double-stranded (ds) DNA antibodies in sera from patients with systemic lupus erythematosus (SLE) using the Crithidia luciliae assay method were compared by conventional titration vs the titration emulation method (ImageTiter) to evaluate whether the latter assay can replace manual titration. Titers by the two methods were identical or within one dilution in 98% (41/42) of samples. A single sample showed a two-dilution difference. Titration emulation showed a tendency to under-estimate the titer of high titer anti-dsDNA samples, although the difference was small. Titration emulation is a suitable alternative to the conventional titration method, offering an accurate and cost-effective approach to quantification of anti-dsDNA antibodies.
Baranowska-Daca E, Choi YJ, Barrios R, Nassar G, Suki WN, Truong LD.
Renal Pathology Laboratory, Department of Pathology, and the Renal Section, Department of Medicine, the Methodist Hospital and Baylor College of Medicine, Houston, TX. Accepted for publication May 23, 2001.
Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis. HUM PATHOL 32:1125-1135. Copyright 2001 by W.B. Saunders Company
PMID: 11679948 [PubMed - in process]
Ulcerating plantar keratoderma in association with systemic lupus erythematosus.
Grossberg EB, Scherschun L, Fivenson DP.
Department of Dermatology, Henry Ford Health System, Detroit, Michigan 48202-2608, USA.
This report highlights the finding of ulcerative plantar keratoderma in two patients with systemic lupus erythematosus (SLE). Both patients suffered from painful plantar ulcerations and fissures; in one patient there was diffuse desquamation over the entire plantar surface, while the other patient's lesions were focal and accentuated over weight-bearing surfaces. Other etiologies for keratoderma including papulosquamoua disease, contact dermatitis, tinea and primary keratodermas were excluded. Both patients were resistant to multiple topical therapies including super-potent topical corticosteroids, vitamin D analogues and retinoids, but did report moderate relief with hydrocolloid dressings applied over super-potent topical corticosteroids and pressure off-loading measures. Lupus-associated keratoderma can be recurrent and recalcitrant to treatment, often necessitating aggressive therapy and particular attention to advanced wound care methodologies. While not a specific cutaneous sign of lupus, it should be recognized as a cause for considerable morbidity.
PMID: 11678455 [PubMed - in process]
CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus.
Liu MF, Wang CR, Lin LC, Wu CR.
Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China. Mfliu@mail.ncku.edu.tw
Cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a structural homologue of CD28, has been reported to be an important negative regulator of autoimmune diseases. Recent studies showed that CTLA-4 gene polymorphism was associated with several kinds of human autoimmune diseases, suggesting that CTLA-4 gene is probably a general susceptibility gene to autoimmune disease. The present study was conducted in Chinese to determine whether there is any association of the CTLA-4 gene polymorphism with the development of systemic lupus erythematosus (SLE). CTLA-4 gene polymorphism in promoter and exon 1 was detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 81 patients with SLE and 81 normal controls. The results showed that there were no statistically significant differences in both exon 1 and promoter gene polymorphism between SLE patients and normal controls. The preliminary study does not suggest an association of the known polymorphism in exon 1 and promoter of CTLA-4 gene with Chinese SLE. However, SLE is a very heterogeneous syndrome and CTLA-4 gene polymorphism might correlate with some specific clinical features. To exploring this possibility, subgroup analysis in more patients needs to be performed.
PMID: 11678454 [PubMed - in process]
Geographical variation in mortality from systemic lupus erythematosus in the United States.
Walsh SJ, DeChello LM.
Department of Community Medicine, School of Medicine, University of Connecticut Health Center, Farmington 06030-6325, USA. walsh@nso.uchc.edu
The aim was to identify demographic and environmental factors that affect the incidence and course of systemic lupus erythematosus (SLE) by studying geographical variation in mortality from the disease. Counts of SLE deaths during a 10-y period were determined for each of the 3111 counties in the United States. The counts were subjected to statistical techniques for detecting spatial clusters with significantly higher or lower mortality than expected. Census data were used to compare attributes of the resulting clusters. Four clusters with significantly elevated SLE mortality were identified. They were centered in Alabama, Arkansas, Louisiana and New Mexico and had 41-65% more SLE deaths than expected. Four other clusters with significantly low mortality were centered in Minnesota, Vermont, Virginia and Washington and had 32-44% fewer deaths than expected. Comparison of SLE mortality rates between the New Mexico and Vermont clusters yielded relative risks of 3.2, 3.4 and 5.9 for white, black and other race women, respectively, and of 2.1, 5.2 and 'undefined' for white, black and other race men. Census data showed that the clusters with elevated mortality had higher poverty rates and/or greater concentrations of ethnic Hispanics than those with lower mortality. SLE mortality rates show great regional variation within the United States. The variation appears to reflect, in part, geographical patterns in socioeconomic status and in the distribution of persons of Hispanic origin.
Titration emulation: a computer-assisted technique that simplifies the quantification of anti-dsDNA antibodies using the Crithidia luciliae assay.
Satoh M, Behney KM, Mizutani A, Richards HB, Hutson AD, Reeves WH.
Department of Medicine, University of Florida, Gainesville 32610-0221, USA. satohm@medicine.ulf.edu
Titers of anti-double-stranded (ds) DNA antibodies in sera from patients with systemic lupus erythematosus (SLE) using the Crithidia luciliae assay method were compared by conventional titration vs the titration emulation method (ImageTiter) to evaluate whether the latter assay can replace manual titration. Titers by the two methods were identical or within one dilution in 98% (41/42) of samples. A single sample showed a two-dilution difference. Titration emulation showed a tendency to under-estimate the titer of high titer anti-dsDNA samples, although the difference was small. Titration emulation is a suitable alternative to the conventional titration method, offering an accurate and cost-effective approach to quantification of anti-dsDNA antibodies.