Overview
Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple autoantibodies that involves multiple systems and organs throughout the body. Lupus Nephritis (Lupus Nephritis) is the most common and serious complication of SLE. Severe renal complications can directly or indirectly affect the survival rate of SLE patients. It becomes one of the major causes of death in this disease.
[Epidemiology
The incidence of lupus nephritis varies depending on the ethnicity studied and the different diagnostic criteria adopted. The incidence of SLE is much greater in women than in men, with a ratio of 8-13:1. However, the rate of renal involvement in male patients is almost the same as in female patients. The age of onset of SLE is predominantly in younger patients, with more than 85% of patients younger than 55 years of age. About 25%-50% of SLE patients have significant renal complications at the time of diagnosis, and about 60% of SLE patients will develop nephropathy during the course of their disease.
[Pathogenesis].
Although multiple immunologic abnormalities in SLE patients have been noted by scholars, the direct etiology of SLE remains unclear. Overall, SLE is a disease of auto-tolerance disorder caused by abnormal immune regulation. Currently, it is believed that the pathogenesis of SLE is mainly focused on immunological abnormalities, genetic factors, hormonal and environmental factors.
[Clinical manifestations
Although the renal manifestations of SLE mainly involve female patients, the clinical manifestations are similar in male and female patients. The clinical manifestations and the degree of renal involvement are similar in adults and children. The clinical manifestations of lupus nephritis are as complex as other systemic manifestations. The renal clinical manifestations occur concurrently with or after the onset of SLE and follow a recurrent clinical course. The clinical presentation is usually consistent with renal pathology, but some patients can present with more severe vascular and tubulointerstitial lesions and less severe glomerular lesions.
The extra-renal clinical manifestations of lupus nephritis are complex and varied because lupus is a systemic disease that accumulates multiple organs throughout the body, and its clinical manifestations and disease regression are complex and varied.
Skin lesions: 55%-90% of skin and mucous membranes are affected, including pteroid erythema, oral and nasal mucosal ulcers, discoid erythema, and subacute skin lesions.
Joint lesions: arthritis and arthralgia are the most common, with an incidence of approximately 95% or more.
Pulmonary lesions: pleurisy is the most common, with an incidence of about 40-60%, sometimes with pleural effusion.
Cardiovascular lesions: The most common is pericarditis. Cardiovascular comorbidities are clinically combined in 1/4 of patients, and the autopsy positivity rate is as high as 2/3.
Neurological lesions: Neurological lesions are clinically diverse and can be difficult to differentiate from hormone-related neurological symptoms. They include cognitive impairment, headache, altered state of consciousness (rigidity to coma), seizures, stroke, optic neuritis, and peripheral neuropathy.
Hematologic lesions: Hematologic complications including lymphadenopathy can involve 50% of patients with SLE. Nearly half of the patients are associated with anemia, manifested as hemolytic anemia and positive direct Coomb’s test.
(Ancillary tests]
(1) Blood routine: about 80% of patients have moderate anemia, orthocytic orthopigmented anemia, about 50% of patients have decreased white blood cells, usually less than 4×109/L, and lymphocytopenia is especially obvious, about 20% of patients have mild decrease of platelets, but individual can be less than 30×109/L, about 25% of patients have decreased whole blood cells. Coomb test is positive in some patients, suggesting hemolytic anemia.
(2) Blood sedimentation: about 90% of the patients have significantly increased blood sedimentation.
(3) Serum protein electrophoresis: serum γ globulin or α2 and β globulin are increased during the active period and return to normal after treatment.
(4) Serum immunoglobulin and complement assay: IgA, IgG and IgM may be elevated. Serum total complement CH50 decreases, C3, C1q and C4 decrease, especially C3 can be significantly decreased when lupus is active. Complement levels were negatively correlated with lupus activity. SLE can be 100% established when the patient has positive serum anti-ds-DNA antibodies and decreased complement C3. Usually C3 and C4 levels usually fall before obvious clinical changes, and a generalized decrease in complement levels is more clinically significant than a decrease in C3 alone or often C4 alone. In contrast, a rebound in complement levels often indicates improvement of renal disease. Cryoglobulinemia suggests immunoglobulin complex formation.
(5) Autoantibody testing.
Plasma antinuclear antibody profile: It is a sensitive screening indicator for SLE commonly used in clinical practice. a titer ≥1:10 is considered positive and greater than 1:20 is clinically significant. more than 1:40 is specific for the diagnosis of lupus nephritis. the sensitivity of ANA antibody profile is >90% and specificity is >70%. the titer of ANA antibody is not related to the severity of renal disease.
Anti-ds-DNA antibodies: are specific for the diagnosis of SLE, but are less sensitive, with approximately 3/4 of active SLE being positive at first diagnosis. Anti-ds-DNA antibodies are directly related to disease activity and prognosis.
Anti-Sm and anti-Rib antibodies: are hallmark SLE antibodies with a specificity of up to 99%, but do not represent disease activity.
Anti-RNP antibodies: seen in 26%-45% of SLE patients. Patients with positive anti-RNP antibodies often have Raynaud’s phenomenon.
Anti-histone antibodies: 50-70% of patients are positive for anti-histone antibodies, with good specificity, occasionally seen in rheumatoid arthritis and dry syndrome, etc.
Anti-Ro/Serum amyloid A (SSA) antibodies and anti-Ro/SSB autoantibodies: Anti-Ro/SSA antibodies are autoantibodies against protein components in cytoplasmic RNA, with a positivity rate of 25-30%. Anti-Ro/SSB autoantibodies are autoantibodies against nuclear RNP, with a positivity rate of 5%-15%.
Rheumatoid factor: 20-30% of SLE patients are positive for RA factor, but a non-specific indicator.
Other antibodies: SLE is also often combined with a variety of autoantibodies, such as anti-erythrocyte antibodies in hemolytic anemia and ANCA positivity in necrotizing vasculitis.
(6) Positive lupus cells are caused by sensitization and destruction of blood leukocytes by antinuclear antibodies, etc., and release of nuclei, which in turn are phagocytosed by multinucleated leukocytes.
(7) Elevated FDP and increased fibrin degradation products in blood and urine.
(8) False-positive syphilis serologic test by venereology.
[Renal pathology examination].
Pathologic staging of lupus nephritis (ISN/RPS, 2003) Type I minimal lesion lupus nephritis (Class Ⅰ, Minimal mesangial lupus nephritis) with normal glomeruli on light microscopy but immunofluorescence (and/or electron microscopy) showing immune complex deposition Type II mesangial proliferative lupus nephritis (Class Ⅱ, Mesangial Proliferative lupus nephritis (Class II, Mesangial proliferative lupus nephritis) is a mild hyperplasia of simple thylakoid cells or with thylakoid stromal hyperplasia, and a widening of the thylakoid zone with immune complex deposition in the thylakoid zone is seen on light microscopy. Focal subendothelial immune complex deposition with or without thylakoid hyperplasia is seen in active or inactive lesions, segmental or globular glomerular proliferative lesions, or crescent formation, but less than 50% of all glomeruli are involved.
III (A) Active lesions: focal hyperplastic lupus nephritis *III (A/C) Active and chronic lesions: focal hyperplastic and sclerosing lupus nephritis III (C) Chronic inactive lesions with glomerulosclerosis: focal sclerosing lupus nephritis **The proportion of glomeruli with active and sclerosing lesions should be indicated with tubular atrophy, renal interstitial cell infiltration and fibrosis, renal vascular sclerosis, and other vascular Severity (mild, moderate, severe) and proportion of lesions Type IV diffuse lupus nephritis (Class Ⅳ, Diffuse lupus nephritis) active or inactive lesions with diffuse segmental or globular intra-glomerular proliferative lesions, or crescent formation, involving more than 50% of all glomeruli, with diffuse subendothelial immune complex deposition seen with or without thylakoid hyperplasia. There are two subtypes: (IV-S) lupus nephritis: segmental lesions in more than 50% of the glomeruli; and (IV-G) lupus nephritis: globular lesions in more than 50% of the glomeruli.
Mild or non-cellular proliferative lupus nephritis with diffuse platinum ear-like lesions is also classified as type IV diffuse lupus nephritis IV-S (A) Active lesion: diffuse segmental proliferative lupus nephritis *IV-G (A) Active lesion: diffuse globular proliferative lupus nephritis IV-S (A/G) Active and chronic lesion: diffuse segmental proliferative and sclerosing lupus nephritis IV -G (A/G) Active and chronic lesions: diffuse spheroid hyperplastic and sclerosing lupus nephritis IV-S (C) Chronic inactive lesions with sclerosis: diffuse segmental sclerosing lupus nephritis ** IV-G (C) Chronic inactive lesions with sclerosis: diffuse spheroid sclerosing lupus nephritis should indicate the proportion of glomeruli with active and sclerotic lesions should indicate tubular atrophy, renal interstitial cells The severity (mild, moderate, or severe) and proportion of type V membranous lupus nephritis (Class Ⅴ, Membranous lupus nephritis) with diffuse thickening of the glomerular basement membrane and visible globular or segmental subepithelial immune complex deposition with or without thylakoid hyperplasia. Type V lupus nephritis may be combined with type III or IV lesions, then a compound diagnosis should be made, such as III+V, IV+V, etc., and may progress to type VI sclerosing lupus nephritis Type VI severe sclerosing lupus nephritis (Class Ⅵ, Advanced sclerosing lupus nephritis) More than 90% of the glomeruli show spherical sclerosis and no longer have active lesions * Active lesions. Glomerular intracapillary hyperplasia, moderate to severe thylakoid hyperplasia, membrane hyperplasia, fibrinoid necrosis, cellular or cellular fibrous crescent formation, leukocyte infiltration, nuclear fragmentation, massive subendothelial immune complex deposition and platinum ear-like structure formation, microthrombosis, etc., interstitial single nucleated cell infiltration, and fibrinoid necrosis of the renal vessel wall; ** inactive or chronic lesions: diffuse thickening of the glomerular basement membrane, the Glomerular segmental or globular sclerosis, fibrous crescent formation, tubular atrophy, interstitial fibrosis, renal vascular sclerosis
[Calculation of activity and chronicity index].
Immunosuppression can reduce the pathological changes though. However, pathological reduction does not equate to clinical improvement. Some chronic lesions such as glomerulosclerosis, tubular atrophy, and interstitial fibrosis are irreversible and continue to progress even after active lesions such as necrosis or proliferation are controlled.
The more commonly used scoring system is Austin’s activity index (score 0-24) intracapillary hyperplasia 0-3 leukocyte infiltration 0-3 subendothelial hyaline material deposition 0-3 fibrinoid necrosis/nuclear fragmentation 0-6 cellular crescent 0-6 interstitial crescent formation 0-3 chronicity index (score 0-12) glomerulosclerosis 0-3 fibrous crescent 0-3 renal tubular Atrophy 0-3 interstitial fibrosis 0-3 According to this scoring system, active lesions included 6 items: intra-glomerular capillary hyperplasia, intra-glomerular neutrophil infiltration, platinum ear phenomenon and hyaline thrombosis, nuclear fragmentation and fibrinoid necrosis, cellular crescent and interstitial inflammatory reaction. Each item was scored 0-3 points, for a total of 24 points. Glomerular lesions (intracapillary hyperplasia, platinum ear phenomenon, hyaline thrombosis, nuclear fragmentation and fibrinoid necrosis, and cellular crescent) were scored as follows: 0, no lesion; 1+ less than 25% glomerular involvement; 2+, 25%-50% glomerular involvement; 3+ greater than 50% glomerular involvement. Neutrophil infiltration was defined as a white blood cell count greater than 2 per glomerulus, according to mild, moderate, and severe degrees and scores of 1, 2, and 3, respectively. Fibrinoid necrosis and cellular crescent doubled the score due to their high prognostic impact. Interstitial inflammation was scored as 0, 1, 2 and 3 according to the degree of absence, mild, moderate and severe, respectively. Chronicity index points in segmental or globular glomerulosclerosis and fibrous crescent if less than 25% glomeruli subject to accumulation 1+, 25%-50% glomeruli subject to accumulation 2+, greater than 50% accumulation 3+. Renal tubular atrophy and interstitial fibrosis were scored according to mild, moderate, and severe degrees and 1, 2, and 3, respectively.
Using this score criterion, Austin et al. found that the AI index could moderately suggest renal prognosis, with a 10-year renal survival rate of 60% in patients with an AI index greater than 12, but neither active lesion alone could predict renal prognosis. In contrast, the CI index was more meaningful than the AI index in terms of renal prognosis. a CI index score of 1 was associated with a 10-year renal survival rate of 100%, a score of 2-3 was associated with 68%, and a score greater than 4 was associated with only 32%. This suggests that even a low chronicity index can indicate a poor prognosis. Moreover, each chronicity index is indicative of prognosis, especially renal tubular atrophy.
Diagnosis and differential diagnosis
Diagnostic criteria for SLE.
The 1982 criteria of the American Rheumatism Association are widely used, and there are 11 items.
(1) Cheek erythema A fixed erythema throughout the cheek or above the skin, often without involvement of the nasolabial fold area.
(2) Discoid lupus Rising erythema covered with keratinized scales and follicular plugs, with atrophic scarring seen in older lesions.
(3) Photoallergy Skin allergy caused by sunlight exposure.
(4) Oral ulcers Painless ulcers on the oral or nasal area.
(5) Non-erosive arthritis Involving 2 or more peripheral joints with joint pain or exudate.
(6) Plasmacytitis Pleurisy: chest pain, pleural friction sounds or pleural effusion Pericarditis: abnormal electrocardiogram, pericardial friction sounds or pericardial effusion
(7) Renal lesions Proteinuria: >0.5g/L or >+++. Tubular pattern: red blood cells, hemoglobin, granular tubular pattern or mixed tubular pattern are seen.
(8) Neurological abnormalities Convulsions: non-drug or metabolic disorders such as uremia, ketoacidosis or electrolyte disorders due to psychosis: non-drug or metabolic disorders such as uremia, ketoacidosis or electrolyte disorders due to
(9) Hematologic abnormalities Hemolytic anemia with reticulocytosis Leukopenia.