Webelieve that under reporting of lupus in Pakistan has given basis to the falsebelief that SLE is not a common disease in Pakistan.
SLE is very common in ourcommunity and the true frequency of SLE, however, can only be obtained byconducting a community-based study and creation of registry protocols. It ispretty straightforward that the more SLE patients screened more chances to findpatients with renal involvement. One study that is worth mentioning here inwhich basically population based frequency of systemic lupus erythematosus andlupus nephritis has been calculated 144 in south east Michigan from2002-2004. They used American College of Rheumatism criteria to pick patientsof Systemic Lupus erythematosus. Data were collected by various abstractors whohad completed standardized, rigorous training, which included completion ofpilot abstractions which were reviewed in detail by therheumatologist-investigators against the source documentation. Continual assuranceof quality of data abstraction included re abstraction of 5% of the records, aswell as physician review of all abstractions and provision of feedback.
For eachpotential case, researchers manually reviewed all available records. They foundoverall age-adjusted prevalence and incidence (ACR definition) per 100,000persons were 5.5 (95% confidence interval 95% CI 5.0–6.1) and 72.8 (95% CI70.8–74.
8) and among females, the incidence was 9.3 per 100,000 persons and theprevalence was 128.7 per 100,000 persons.
Only 7 cases were estimated to havebeen missed, adjustment for which did not affect the rates. Systemic lupuserythematosus was 2.3-fold higher in black persons than in white persons, and10-fold higher in females than in males. Among incident cases, the mean ± SDage at diagnosis was 39.
3 ± 16.6 years. Black SLE patients had a higherproportion of renal disease and end-stage renal disease (ESRD) (40.5% and15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%,respectively).
Black patients with renal disease were diagnosed as havingsystemic lupus erythematosus at younger age than white patients with renaldisease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). We know estimating the frequencyprevalence of systemic lupus erythematosus (SLE) in the general population ischallenging and resource-intensive to perform.
In part, this is due to aprotean and systemic nature of the disease and the attendant diagnosticcomplexity that requires the synthesis of a multitude of clinical observationsand laboratory findings, often obtained from a variety of health care settings.In the United States, the fragmented health care system and lack of existinginfrastructure suitable for the surveillance of autoimmune diseases such assystemic lupus erythematosus further complicates the implementation ofpopulation-based measures to ascertain and validate cases. Epidemiologic data isimportants to our understanding of the risk and burden of disease in thepopulation. However, such data are challenging and resource intensive to derivein a fragmented health care system and for diseases such as systemic lupuserythematosus, in which a heterogeneous constellation of clinical andlaboratory features is essential to establish a diagnosis. Surveillance outsideof the tertiary care setting is imperative for recording the full spectrum ofsystemic lupus erythematosus, in order to identify cases receiving health carein other settings. In the socio-demographically diverse MILES source populationof 2.4 million, there were, on average, 133 new cases and 1,708 prevalent casesof systemic lupus erythematosus annually during 2002–2004, yieldingage-standardized incidence and prevalence estimates per 100,000 persons of 5.5and 72.
8, respectively. Using more complete case-finding sources, they wereable to quantify at a new level of statistical precision the higher risk andburden of SLE among women and minorities in the general population of the US.Themajority of previously available data on the epidemiology of systemic lupuserythematosus were derived from predominantly homogeneous populations of Europeandescent.
Though caution was exercised when comparing results between studiesthat was heterogeneous in terms of methodologies and population structures, inrelation to the weighted data, their rates in Michigan appear to be similar forSLE incidence, though 3-fold higher for SLE prevalence. The largerprevalence-to-incidence ratio in their population, coupled with the higherprevalence range in the more recent review, suggests that prevalence may beincreasing, in part due to improved survival, over the last 2 decades. The netmigration in Michigan (i.e., the balance of in- and out-migration) from 1985through the end of the surveillance period was relatively stable, includingthat among young adults (a reasonable proxy for a “healthy” population subset).However, the possibility that persons with preexisting lupus migrated into thesource population in order to be more proximate to medical care cannot beexcluded.Theyfound a female-to-male incidence ratio of 6.2:1 and a female-to-male prevalenceratio of 10.
1:1; hence, males accounted for a higher proportion of newlydiagnosed cases as compared to existing cases in the overall population, apattern that pertained to both black patients and white patients. Studiesexamining race have documented higher rates in persons of African descent: astudy from Allegheny County, PA (for the years 1985–1990) found an ~3-foldincidence of SLE among black females versus white females (9.2 versus 3.5 per100,000 persons) In their population, black persons had the highest risk andburden of SLE, with a 2.1-fold higher incidence and a 2.
3-fold higherprevalence (1 in 537 black females) than white persons, ratios somewhat smallerthan those reported elsewhere. The ability to compare disease patterns in otherracial and ethnic groups is limited by the small numbers of these minorities inour geographic region, though data suggest that black persons have a higherprevalence of SLE than Asian/Pacific Islander or Hispanic persons.Asshown by the age-specific incidence rates, systemic lupus erythematosus beganearlier in the reproductive years in black females. In late childhood, therewas already a trend for black girls to have an increased incidence compared towhite girls, and in the 20–50-year range, there was an early incidence peak inblack women, as compared to statistically lower levels that plateaued amongwhite women. The incidence rates in black versus white women did not differsignificantly. Higher genetic load (number of SLE-susceptibility risk alleles)has been associated with earlier disease onset among African American, but notEuropean American, SLE patients and gene–environment interactions may furtherunderlie observed racial differences in the natural history of this disease.
Thisstudy had several limitations. First, it was based on review of medicalrecords, rather than direct patient examination, as most population-basedepidemiologic studies must. Second, race and ethnicity were ascertained fromrecords, not self-reports, which would be the gold standard.
Misclassificationmay be a particular concern for persons of Hispanic/Latino ethnicity, sincemany medical records systems do not assess Hispanic ethnicity as a separatevariable from race, which in theory, could lead to underestimation. Third,although we tried to reach all targeted health care sources, a few (see thecase ascertainment section above) did not permit access, and the slowcooperation of others necessitated active record reviews through 2011,requiring increased allocation of resources in order to complete the plannedsurveillance activities. The nonparticipating sites did not appear to differsystematically from the participating sites in terms of the demographics of thepopulations served or other discernible features.
Fourth, they have likelyunderestimated incident and prevalent cases, as there may be undiagnosed casesin the community that have not reached the health care system for screening anddiagnosis, and other cases may have received care outside the catchment area.However, the capture–recapture analyses estimated that surveillance programmissed only 7 cases in the source population, pointing to highly effectivemethods of defining catchment areas (based on a pilot analysis of health careutilization patterns) and case ascertainment. Fifth, they were unable to enlistthe systematic cooperation of primary care providers for even morecomprehensive findings, but the interactions we did have suggested that primarycare practices are likely to refer SLE patients and are therefore unlikely torepresent a large source of additional cases.Thisstudy also has several strengths. First, it included multiple case-findingsources, including health care facilities in a county contiguous to the sourcepopulation, which helped to ensure complete ascertainment in a mobilepopulation. Second, for each patient, there was comprehensive abstraction andsynthesis of detailed clinical and laboratory data from multiple sources.
Withthe public health authority from the MDCH enabling our access to all relevantrecords, a thorough profile could be constructed for the majority of patients.In some cases, the diagnosis of lupus could be confirmed only after combiningdata from several hospitals or physicians. Third, as noted above, the use of 2analytical case definitions (ACR and rheumatologist definitions) independentlyconfirmed the diagnoses in the majority of patients and accommodated theclinical uncertainty of classifying SLE. The rheumatologist rates may beconsidered to yield conservative estimates and, thus, serve as a validated”lower bound” for the estimation of SLE.
Fourth, the collaboration withcolleagues from the CDC, the Georgia Lupus Registry, and the respective statehealth departments for the methods and infrastructure development can serve asa prototype for the implementation of other SLE registries, which will enhanceopportunities for comparison of SLE statistics across sites. Indeed, newregistries based on this framework have been initiated in regions with greaterrepresentation of other minority groups (Asian/Pacific Islander,Hispanic/Latino, and American Indian/Alaska Native groups).Basedon this comprehensive, population-based surveillance program, our dataunderscored substantial levels of confirmed systemic lupus erythematosus caseswhich of course influenced frequency of lupus nephritis. Our purpose to mentionthe above study in detail was to depict that even in such a well-equipped setupas United States they had limitations in their study. Such data support a focus of medical resourceson early diagnosis and improved treatment of lupus nephritis. We also need to have specific SLE/LUPUSregistry such as Georgia lupus registry. In the 1950’s, systemic lupuserythematosus (SLE) was thought to be rare, predominantly affecting femaleswith light hair, fair skin, and “inability to tan”. An epidemiologic study from1956–65 showed for the first time the higher burden of disease in black womencompared to their white counterparts.
We now appreciate the disproportionateburden of SLE on women, particularly in their childbearing years, and incertain racial groups. These epidemiologic studies advanced our understandingof the burden of SLE but were limited in their ability to find all cases in thepopulation and thus describe the full spectrum of diagnosed systemic lupuserythematosus.Giventhe recent significant increase in awareness of and research in SLE and LN,along with the availability of innovative techniques, the purpose of this GeorgiaLupus Registry (GLR) study was to advance the epidemiologic understanding ofSLE by doing more complete case finding in a targeted population, avoidingreferral bias in a particular institution, using available case definitions tobetter define the incidence and prevalence of diagnosed SLE, and characterizingindividuals with this disease from a population perspective. The GLR is one oftwo recently completed Centers for Disease Control and Prevention (CDC) fundedpopulation-based lupus registries designed to minimize many of the limitationsof previous studies. An innovative tool in this approach is the use of thestate public health surveillance exemption to the Health Insurance Portabilityand Accountability Act (HIPAA) to obtain greater access to protected healthinformation without requiring individual patient consent, a limitation that canbias findings.
This new and powerful approach allows for an unprecedentedcompleteness of case finding from multiple sites of ascertainment throughoutthe targeted community. Coupled with detailed training of abstractors, strictquality control of data gathering and processing, many sources of caseascertainment that reduced bias from a consent process or institution type, andthe high number of cases, this study provided more reliable population-basedestimates of true incidence and prevalence of SLE than previously reported. The frequency and severity of lupus nephritismay be related to the patients’ racial background and studies have suggestedthat there are certain nephropathy susceptibility genes that predisposing tolupus nephritis 134. Although all of the evidence suggeststhat a genetic predisposition plays a major role in development of systemiclupus erythematosus (SLE) and/or lupus nephritis (LN), the susceptibility genesare mostly unknown. The problem in identifying susceptibility genes is due inpart to multiple genes with variable genetic effects and the diverse geneticbackgrounds of human populations. In human SLE, genes of early components ofcomplements as well as many polymorphic genes (including the MHC class II andclass III, Fc?R, mannose-binding protein, IL-6, Bcl-2, and IL-10 genes) havebeen linked with SLE or LN by population-based case-control or within-casestudies.
The contribution of some of these disease-associated genes to the presenceor absence of clinical manifestations has been further tested in mice withtargeted alteration of the specific candidate gene. In addition to SLEsusceptibility genes, there may be a separate set of nephropathy susceptibilitygenes predisposing to LN as suggested by the familial clustering of end stagerenal disease in African-Americans with Lupus Nephritis. The availability of tightlypacked genetic markers spanning the entire genome has enabled theidentification of chromosomal regions linked to disease susceptibility geneswithout previous knowledge of the gene function. Our group has used knownmurine lupus susceptibility loci as a guide, and conducted linkage analysis ofgenetic markers located within a specific, possibly syntenic human chromosomalregion. Evidence for linkage of a chromosome 1q41-42 region was observed inSLE-affected sib pairs from multiple ethnic groups.
More recently, severalgroups have reported results of genome scans of SLE-affected sib pairs orpedigrees. Given the morbidity associated with LN, the ability to accuratelyidentify SLE patients destined to develop LN could shift the current managementparadigm from treatment to prevention. Although it is not likely that CKD andESRD can be avoided completely, because many patients present with LN as theinitial manifestation of their SLE, a preventative management strategy couldsignificantly reduce CKD and ESRD. For example, SLE patients destined todevelop LN could be followed much more closely, perhaps with home monitoring ofthe urine so kidney biopsy and treatment could be started without delay.Alternatively, such patients could be considered for pre-emptive therapy toattenuate autoimmunity before any clinical manifestations of kidney involvementare apparent. Although it is currently not possible to determine a priori who with SLE will developLN, several investigations of lupus genetics have approached this question. Lupus Nephritis remains also major cause ofmorbidity and mortality particularly among patients of Hispanic andAfrican-American ethnicity SLE patients with renal involvement are at a higher riskof dying of this disease 135,136. Generally renal involvement is more commonin Blacks, Indians and Chinese, with lesser prevalence in Caucasians and Arabs137, 138.
Paradoxically,our study showed a frequency of renal involvement (86%) as compared to theIndians (73%) 137, Blacks (78%) 140, Chinese (54%) 138 and Arabs 12 (54%)139. The mean age of the study group patients at presentation was 27.31 ± 7.45years. Our study also showed LN class 4 being the most common histopathologicalfinding diagnosed when patients underwent renal biopsy. A similar finding wasobserved by Vineeta Shobha ET, al.
141. There has been a recent updateregarding renal biopsy 145. Although the decision to perform a kidney biopsyin SLE patients when there is clinical evidence of renal involvement seems straightforward,it has become somewhat controversial because of a prevailing view that allforms of LN can be adequately treated with corticosteroids plus mycophenolatemofetil (MMF). As the therapy of LN moves beyond the currently available non targetedimmunosuppressive regimens of high-dose corticosteroids plus cyclophosphamideor MMF to interventions that focus on specific immune pathways, a morecomprehensive picture of renal pathology through molecular imaging of thekidney biopsy may be desirable. The immune pathways active in the kidney at thetime of lupus nephritis diagnosis vary considerably between patients.Nonetheless, the kidney biopsy is important to define the nature of renalinvolvement. Although immune-complex–mediated GN is the most common cause ofkidney disease in systemic lupus erythematosus, there are other mechanisms thatresult in renal injury which can only be diagnosed with a biopsy, and require adifferent approach to management than immune-complex LN 145.
There was apreponderance of female patients in the study. This finding is similar to mostof the studies of SLE that have shown a predominance of females 142,143. Thelimitation of our study were that it was a single center study and may ifplenty of systemic lupus erythematosus patients were screened the actualfrequency would have been different