| disease | Lupus Erythematosus |
| alias | Lupus Erythematosus, LE |
Systemic lupus erythematosus (LE) is an autoimmune inflammatory connective tissue disease that predominantly affects young women and involves multiple organs. In recent years, with increased understanding of the disease and continuous improvements in immunological testing techniques, more cases of early-stage, mild, and atypical presentations have been identified. Some patients, except for those with diffuse proliferative glomerulonephritis, may experience spontaneous remission. Others exhibit transient episodes that completely resolve after a few months. The combined use of traditional Chinese and Western medicine, along with the rational application of corticosteroids and immunosuppressants, has significantly improved the prognosis of this disease in recent years.
bubble_chart Epidemiology
This disease is widely distributed around the world, and its exact incidence rate remains unclear. Reported incidence rates vary across different countries and regions. In China, Huang Mingxin et al. (1985) conducted a survey of 32,000 textile workers in Shanghai, revealing a prevalence rate of 70.41 per 100,000. Xu Deqing et al. (1992) surveyed 26,000 postal workers and residents in Guicheng Town, Guangzhou, finding a prevalence rate of 30.13 per 100,000. The annual incidence of SLE varies by region, ethnicity, gender, and age. In terms of gender, females significantly outnumber males, with a male-to-female ratio of approximately 1:8–9 among individuals of childbearing age, and about 1:2–3 among the elderly and young children. The onset of the disease is most common in young and middle-aged adults, with about half of cases occurring between the ages of 20 and 40. The younger the age of onset, the higher the likelihood of familial occurrence.
bubble_chart EtiologyThe etiology of this disease is unknown, but recent studies have confirmed that it is characterized by various immune response abnormalities. The factors causing immune dysfunction may be multifaceted.
(1) Genetic background: The prevalence of this disease varies among different ethnic groups. Certain strains of mice (NEB/NEWF, MRL1/1pr) spontaneously develop SLE symptoms several months after birth. Family studies show that approximately 10–20% of first- and second-degree relatives of SLE patients may develop similar conditions, with some exhibiting hyperglobulinemia, various autoantibodies, and abnormal T-suppressor cell function. The concordance rate for monozygotic twins is 24–57%, while for dizygotic twins, it is 3–9%. HLA typing indicates that SLE patients are associated with HLA-B8, -DR2, and -DR3. Some patients may also have deficiencies in complement components C2 and C4, or show significant correlations with TNFα polymorphisms. Recent findings suggest that homozygous C2 gene deficiency and high -DQ frequency are closely related to DSLE. T-cell receptor (TCR) is also linked to SLE susceptibility, and low levels of TNFα may be the genetic basis for lupus nephritis. All these findings suggest a genetic predisposition to SLE. However, according to a survey of 100 SLE families by Huashan Hospital, in addition to polygenic inheritance, environmental factors also play a significant role.
(2) Drugs: Reports indicate that 3–12% of 1,193 SLE cases are drug-related. Drug-induced cases can be divided into two categories. The first includes drugs that induce SLE symptoms, such as penicillin, sulfonamides, phenylbutazone, and gold preparations. These drugs first cause allergic reactions in the body, then trigger lupus diathesis or latent SLE, or exacerbate existing SLE. Discontinuing these drugs usually does not halt disease progression. The second category includes drugs that cause lupus-like syndrome, such as hydralazine hydrochloride, procainamide, chlorpromazine, phenytoin sodium, and isoniazid. Prolonged use or high doses of these drugs can lead to SLE-like clinical symptoms and laboratory changes. Their pathogenic mechanisms are not fully understood. For example, chlorpromazine is thought to slowly bind to double-stranded DNA and rapidly bind to denatured DNA under UVA exposure. Clinically, skin exposure to sunlight can denature double-stranded DNA, making it more likely to bind with chlorpromazine and form antigenic substances. Hydralazine, on the other hand, binds to soluble nuclear proteins, enhancing the immunogenicity of self-tissue components in the body. Drug-induced lupus-like syndrome typically resolves after discontinuation, though some symptoms may persist. HLA typing shows a significantly higher DR4
(3) Infection Some believe that the onset of SLE is related to certain viral infections (particularly slow viruses). Inclusion-like substances have been found in the glomerular endothelial cell cytoplasm, vascular endothelial cells, and skin lesions of patients. Additionally, patients' sera show elevated viral titers, especially against measles virus, parainfluenza virus types I and II, EB virus, rubella virus, and myxovirus. Furthermore, dsRNA, ds-DNA, and RNA-DNA antibodies are present in patients' sera. The former is typically only found in tissues with viral infections. Under electron microscopy, these inclusion-like substances appear as small tubular reticular structures, 20–25 μm in diameter, clustered in distribution, though they can also be observed in dermatomyositis, scleroderma, and acute sclerosing panencephalitis. Attempts to isolate viruses from tissues containing these inclusion-like substances have been unsuccessful, so the relationship between these substances and viruses remains unconfirmed. Recently, some have proposed that the onset of SLE is closely related to C-type RNA viruses. The authors measured serum interferon in 47 SLE cases, finding elevated levels in 72.3%, classified as type α, including both acid-stable and acid-labile forms. The concentration of interferon paralleled disease activity. It is known that type α interferon is produced by leukocytes stimulated by viruses, polynucleotides, or bacterial lipopolysaccharides, which may indirectly suggest the possibility of viral infection. Others believe that the onset of LE is related to subcutaneous nodules or streptococcal infections.
(5) Endocrine Factors Given that SLE is significantly more common in women than men and often occurs during reproductive years, estrogen is believed to play a role in its development. Studies in animals show that castration alleviates the condition in female NZB mice but worsens it in males, supporting estrogen's influence. The incidence of SLE is notably lower during periods of inactive gonadal function—before age 15 and after age 50. Additionally, oral contraceptives can induce lupus-like syndromes. One study measured sex hormone levels in 20 male SLE patients and found that 50% had elevated serum estradiol levels (compared to 5% in controls), while 65% had reduced testosterone (compared to 10% in controls). The estradiol/testosterone ratio was higher in SLE patients than in healthy controls. These findings support the role of estrogen. Changes in SLE activity during pregnancy are also linked to fluctuations in sex hormone levels. Later in pregnancy, as progesterone levels rise sharply, the progesterone/estradiol ratio increases, leading to relative stability in the disease. Postpartum, when progesterone levels drop, symptoms may worsen again. Recent studies have found elevated prolactin levels in SLE patients, which may cause secondary changes in sex hormones, though further research is needed.
(6) Immune Dysregulation A person with a genetic predisposition to LE may experience immune system destabilization under the influence of the aforementioned triggers. When genetic factors are strong, even mild external stimuli can trigger the disease. Conversely, weaker genetic factors require stronger external stimuli for onset. Immune destabilization leads to regulatory defects in the immune system, including loss of suppressor T cells—both in quantity and function—rendering them unable to regulate B lymphocytes capable of producing autoantibodies. This results in excessive autoantibody production and disease manifestation. Some studies in lupus-prone mice observed early B-cell hyperactivity without apparent regulatory T-cell defects, suggesting that autoantibody-producing B-cell clones escape T-cell control. Even with normal T-lymphocyte regulatory function, these B cells can still produce autoantibodies, a concept known as the "B-cell escape theory" in SLE. Others propose that excessive helper T-cell activity disrupts immune regulation, leading to abundant autoantibody production. Alternatively, overactive monocytes or macrophages may produce certain factors that stimulate helper T cells or directly activate B cells, triggering autoimmunity. The "forbidden clone theory" suggests that immune destabilization causes imbalances in T- and B-cell ratios or between helper/inducer B cells and suppressor/cytotoxic T cells, allowing forbidden lymphocyte clones to proliferate uncontrollably and induce autoimmune pestilence.
Recent studies have found abnormal cytokine secretion in SLE patients. IL-1 is synthesized by mononuclear macrophages, which can promote the proliferation of B cells in SLE, mediate the spontaneous production of IgG by B cells, form immune complexes, and cause tissue injury. MRL/1pr mouse kidney macrophages contain more IL-1 mRNA and can produce large amounts of IL-1 in vitro. IL-1 can induce the production of inflammatory factors such as IL-6, IL-8, and TNF, which are related to the occurrence of lupus nephritis. IL-1 activity is also associated with photosensitivity. Approximately 50% of patients have elevated serum IL-2 levels, and almost all SLE patients have high levels of IL-2R in their serum, with higher levels during the active phase than during the stage of remission. IL-2 is mainly produced by CD+4T cells and serves as a growth factor for T cells. Additionally, SLE patients exhibit elevated serum IL-6 levels, which are more pronounced during the active phase. During central nervous system SLE activity, IL-10 levels rise, leading to increased IgG production. Substantial evidence suggests that IL-10 plays a significant role in the abnormal activation of B cells. The dysregulation of these cytokine networks disrupts immune responses and also contributes to the local nature of disease effects.
The mechanism of autoantigen formation can be attributed to: ① the modification and alteration of tissue components induced by drugs, viruses, bacteria, ultraviolet radiation, etc., which confers antigenicity; ② the release of sequestered antigens, such as thyroglobulin, lens proteins, and sperm, which are normally isolated from the bloodstream and lymphatic system. Trauma or infection disrupts this isolation barrier, allowing these tissue components to enter the bloodstream and come into contact with immunocompetent cells, thereby becoming antigenic substances; ③ the outcome of cross-reactivity.
bubble_chart Pathological Changes
The fundamental pathological changes in LE are mucoid edema of connective tissue, fibrinoid degeneration, and necrotizing vasculitis. Mucoid edema occurs in the early stages of the disease, primarily at the base. Fibrinoid degeneration involves the formation of eosinophilic amorphous substances composed of autoantibodies, complement, DNA antigens, and fibrin, which deposit in the connective tissue, resembling connective tissue degeneration. The connective tissue in the walls of small and medium-sized blood vessels undergoes fibrinoid degeneration, even necrosis, leading to thrombosis, hemorrhage, or local ischemia, constituting necrotizing vasculitis. In visceral organs, Sappan Wood bodies can be observed, which are eosinophilic homogeneous masses formed by the degeneration of nuclei in neutrophils, lymphocytes, and histocytes under the action of corresponding autoantibodies.
The histopathological changes in the skin include epidermal atrophy, liquefaction degeneration of basal cells, increased pigmented cells in the upper dermis, edema of collagen fibers, fibrinoid degeneration, and perivascular and periadnexal infiltration of lymphocytes, with occasional plasma cells and histocytes. Vascular inflammatory changes are often seen in the vessel walls.
In muscles, striated muscles are frequently affected. Small focal fibrinoid degeneration occurs in the connective tissue between and within muscle bundles, accompanied by perivascular infiltration of lymphocytes and plasma cells. Muscle fiber atrophy or hyaline degeneration may also be observed.
In the kidneys, the glomeruli are affected first, followed by tubular lesions. The primary changes include fibrinoid degeneration or focal necrosis of glomerular capillary walls, with hyaline thrombi and Sappan Wood bodies. The basement membrane of capillaries may show focal or, in severe cases, diffuse thickening, forming so-called "wire loop" lesions due to deposits of DNA, anti-DNA antibodies, complement, and fibrin. Besides capillary lesions, the number of glomerular cells may increase, mainly due to mesangial cell proliferation, often focal. The parietal epithelial cells of Bowman's capsule may proliferate, forming crescents. In advanced cases, glomerular fibrosis increases, leading to vascular occlusion or adhesion to the capsule and fibrosis.
In the heart, fibrinoid degeneration occurs in the pericardial connective tissue, accompanied by infiltration of lymphocytes, plasma cells, histocytes, and fibroblasts. Myocarditis changes resemble those in striated muscles. Endocarditis involves connective tissue proliferation and fibrosis of the endocardium and fibroblasts. Repeated episodes lead to verrucous endocarditis, which may affect valve function due to adhesion of valve connective tissue and papillary muscles, with the mitral valve most commonly involved, historically termed Libman-Sacks syndrome.
Pulmonary lesions initially manifest as vasculitis and perivasculitis, later involving the interstitium and parenchyma. Fibrinoid degeneration, necrosis, and hyalinization occur in the interstitial tissue, alveolar walls, and capillaries, accompanied by infiltration of lymphocytes and plasma cells.
In the nervous system, endothelial cell proliferation and lymphocyte infiltration are observed in small vessels and capillaries, along with widespread microthrombi and localized softening foci. Recent findings show immunoglobulin and complement immune complexes on the choroid plexus, and DNA and anti-DNA complexes can be detected in the cerebrospinal fluid.
The spleen exhibits thickened fibrous capsule, follicular hyperplasia, increased plasma cells in the red pulp, and characteristic fibrosis in the central arteries, surrounded by thick, dense concentric collagenous fibrous sclerotic rings, referred to as "onion-skin spleen."
bubble_chart Clinical Manifestations
The Bundick and Ellis classification adopted in the 1950s was: ① localized discoid lupus erythematosus; ② disseminated lupus erythematosus, which was further divided into acute, subacute, and chronic disseminated lupus erythematosus (disseminated discoid lupus erythematosus). As research on this disease became increasingly extensive and in-depth, numerous classification methods emerged thereafter. Kitamura categorized the disease based on the nature of skin lesions into: ① incomplete type (abortive type); ② chronic discoid dry type; ③ chronic discoid exudative type; ④ hyperpigmented type; ⑤ chronic disseminated type; ⑥ acute disseminated type. Martin classified the disease into: ① latent lupus erythematosus; ② cases with specific skin lesions but no systemic symptoms; ③ cases with specific skin lesions and systemic symptoms; ④ cases with systemic symptoms but no specific skin lesions. Gilliam divided patients' skin lesions, regardless of whether they had extra-cutaneous lesions, into: ① chronic cutaneous lupus erythematosus (CCLE), which could be further divided into localized discoid lupus erythematosus, generalized discoid lupus erythematosus, hypertrophic discoid lupus erythematosus, and deep lupus erythematosus; ② subacute cutaneous lupus erythematosus (SCLE); ③ acute lupus erythematosus, which could be divided into facial (malar) erythema, erythema of the face, scalp, neck, upper chest, extensor surfaces of the arms, and dorsum of the hands, and bullous or toxic epidermal necrolysis-like lesions. Some tend to classify it only into discoid and systemic types; the former is further divided into: ① localized discoid type and ② generalized discoid type. Others propose changing the discoid type to cutaneous lupus erythematosus. It is now believed that lupus erythematosus is a spectrum disease, with localized discoid and systemic lupus erythematosus (SLE) as its two extreme types, and subacute cutaneous lupus erythematosus and deep lupus erythematosus in between.
The manifestations are diverse and variable, especially in the early stages of the disease, where symptoms are few and atypical, often presenting with symptoms of only one or two organs, which can easily lead to misdiagnosis. The onset is generally slow and insidious, with discoid and systemic types representing the two ends of the spectrum, which can transform into each other.
(1) Discoid lupus erythematosus (DLE) The male-to-female ratio is 1:2, with the onset age mostly in the 30s. The lesions initially appear as one or several bright red patches, occurring on the face, ears, scalp, etc., ranging from mung bean to soybean size, covered with adherent scales. They gradually expand outward, becoming circular or irregular in shape, with markedly deepened pigmentation at the edges, slightly elevated compared to the center, which is lighter in color with dilated capillaries. Under the scales, there are keratin plugs and enlarged pores, accompanied by varying degrees of cutaneous pruritus and burning sensations. New lesions may gradually increase or remain unchanged for many years, scattered or merging into patches. Lesions on both malar areas and the bridge of the nose may connect to form a butterfly-wing shape. 3% of cases have mucous membrane lesions, mainly on the lips, followed by the cheeks, tongue, and palate, presenting as small grayish-white erosions with scabs, surrounded by a purplish-red halo. The course is chronic, with central atrophy in old lesions, sometimes accompanied by pigmented spots, slightly depressed compared to the surrounding areas. Atrophy on the scalp is often more pronounced, leading to hair loss, known as pseudopelade. Discoid lesions may worsen after exposure to strong sunlight or fatigue. About 5% may transform into the systemic type, and squamous cell carcinoma may rarely develop. If the skin lesions are confined to above the neck, it is called localized discoid lupus erythematosus; if they also involve the upper chest, arms, dorsum of hands and feet, and heels, it is called disseminated discoid lupus erythematosus, of which about 1/5 of cases show systemic manifestations. Lesions that are hypertrophic or verrucous are called hypertrophic or verrucous discoid lupus erythematosus.
(II) Subacute Cutaneous Lupus Erythematosus (SCLE) A special intermediate type first proposed and named by Sontheimer (1979) et al. The male-to-female ratio is approximately 1:2.5. It mostly occurs in individuals in their 30s. The lesions are distributed on the cheeks, nose, ear rims, upper chest, shoulders, back, outer sides of the upper arms, extensor surfaces of the forearms, hands, and dorsal fingers, and are rarely seen below the waist. Occasionally, the lips and buccal mucosa may be involved. The basic lesions present as edematous erythema, which later manifests in two forms: One type spreads outward, forming annular or arc-shaped patterns that may merge into polycyclic or gyrate configurations. These are bright red with raised edematous borders, fine scales on the inner edge, surrounded by a red halo, and central clearing, leaving temporary pigmentation and telangiectasia. Alternatively, they may appear as centrifugal rings, with new rings forming as the central area clears—this is referred to as the annular erythema type. The other type expands into irregular patches covered with scales resembling psoriasis or pityriasis-like lesions—this is called the erythematous papulosquamous type. Follicular plugs and adherent scales are absent. Most patients exhibit one type, though some may have both simultaneously. The lesions persist for weeks or months before resolving without scarring but may recur in the same or different locations. Other features include photosensitivity (27%), Raynaud's phenomenon (20%), and lupus flares (3%). Systemic symptoms may include arthralgia or arthritis (67%), fever (17%), myalgia (20%), serositis (7%), with rare and mild renal involvement. Cardiac and neurological involvement is uncommon. Approximately 20% of cases are accompanied by DLE lesions, and 40% meet the ARA (1982) diagnostic criteria for SLE.
(3) Lupus Erythematosus Profundus (LEP) Also known as lupus panniculitis, it is an intermediate type, predominantly affecting women, with a male-to-female ratio of 1:3–13. The onset age is mostly among young and middle-aged adults. The lesions present as nodules or patches located in the deep dermis and subcutaneous fat tissue, which can occur anywhere but are commonly found on the cheeks, buttocks, and arms, followed by the calves and chest. Cases have also been reported on the breasts, either unilaterally or bilaterally, with varying numbers and sizes ranging from as small as a broad bean to as large as 10 cm in diameter. The edges are clear, skin-colored or light red, firm, and immobile. A few cases may experience pain, described as needle-like, drilling, or tender to touch, and may be accompanied by short-term irregular fever and joint pain. The progression is slow: some nodules remain unchanged while new lesions appear elsewhere; some nodules gradually enlarge or merge with adjacent nodules to form patches; some nodules are absorbed, leaving depressed areas, or necrose and later form atrophic scars; some scars exhibit raised edges like embankments, or necrotic crusts that evolve into DLE lesions. This condition can occur in both SLE and DLE, or exist independently as nodules without typical LE skin lesions. It may appear before, after, or concurrently with LE lesions. The nodules can develop deep within LE lesions or occur alone. This type is unstable and may transition into DLE or SLE lesions, or initially present as DLE or SLE and later develop into LEP.
(4) Systemic Lupus Erythematosus (SLE) The male-to-female ratio of this disease is 1:7–9, with the onset age mostly between 20 and 40, though children and the elderly can also be affected. The clinical manifestations are diverse and complex, including:
1. Skin Rash Approximately 80–85% of patients develop rashes, with 43% exhibiting typical lesions. Some reports indicate 60–72% of cases involve rashes. The lesions are polymorphic, with edematous erythema being the most common, ranging from mung bean to soybean-sized, and may coalesce over the cheeks and nasal bridge to form a butterfly-wing shape. The forehead, earlobes, shoulders, upper arms, extensor surfaces of major joints, dorsa of hands, extensor surfaces of fingers (toes), nail beds, tips and flexor surfaces of fingers (toes), and soles may also be affected. The facial butterfly rash, periungual erythema, and subungual erythema at the distal ends of fingers (toes) are characteristic and often appear early, with the former being a major diagnostic symptom. Another type of lesion is maculopapular, which may be itchy or painful, localized or generalized, sometimes presenting as papules or follicular papules. Occasionally, vesicles, bullae, or hemorrhagic bullae appear on the face and other exposed areas, mostly on pre-existing erythema or normal skin. The fluid in the blisters is initially clear but later turns turbid or bloody, with tense walls. Sun exposure is often a triggering factor. After rupture, the blisters form erosions, ulcers, crusts, and scars. After the erythema and other lesions subside, due to changes in the basement membrane, epidermal dystrophy may occur, leading to epidermal atrophy, pigmentation, and hyperkeratosis. Petechiae and ecchymoses may also appear, caused by prolonged use of high-dose corticosteroids, thrombocytopenia, or small necrotic vasculitis in the skin. Nodules (about 10%) may occur due to thrombotic vasculitis, potentially leading to finger (toe) gangrene, and in severe cases, the dorsa of hands and feet may also be affected, though this is rare. These may result from necrotic vasculitis of small peripheral vessels or cryoglobulinemia, often concurrent with livedo reticularis. Sometimes, erythema multiforme appears, especially in cold seasons. Urticaria-like lesions may also occur, edematous with punctate hemorrhages or bloody blisters, persisting without cutaneous pruritus, caused by necrotic vasculitis of small dermal vessels. Erythromelalgia and disseminated intravascular coagulation (DIC) may also be observed, the latter resulting from immune-mediated injury to large numbers of platelets and red blood cells releasing clotting substances, commonly seen in the terminal stage. Other manifestations include clubbing of fingers, dry and brittle hair with a yellowish appearance, prone to breakage and shedding, varying in length; during remission, hair may regrow. About one-third of patients exhibit photosensitivity and subcutaneous calcium deposits.
Mucous membrane damage involves the lips, cheeks, hard palate, gums, tongue, and nasal cavity, accounting for about 20%. It manifests as erythema with telangiectasia or diffuse flushing, accompanied by punctate bleeding, erosions, and occasionally blisters and ulcers.
2. Fever occurs in approximately 92% or more of cases, with various fever patterns observed. Prolonged low-grade fever is relatively common.
3. Bones and Joints: Over 90% of cases involve joint pain, sometimes accompanied by swelling of surrounding soft tissues. The condition may resemble wind-dampness arthritis, presenting as migratory, polyarticular involvement with redness, swelling, heat, and pain. Alternatively, it may manifest as chronic progressive polyarthritis, often affecting the finger and toe joints, resembling rheumatoid arthritis. In 5–10% of cases, aseptic ischemic osteonecrosis may occur in joints such as the hip, shoulder, and knee, with the femoral head most frequently affected, followed by the humeral head and tibial head, either unilaterally or bilaterally.
4. Kidneys: Approximately 75% of cases involve renal involvement. Renal biopsy reveals kidney damage in 80–90% of cases, while autopsy findings approach 100%. Manifestations include nephritis or nephrotic syndrome. Nephritis presents with red blood cells, white blood cells, casts, and protein in the urine. Early renal function tests may be normal, but progression can lead to uremia. Renal biopsy findings can be categorized into focal proliferative glomerulonephritis and diffuse proliferative glomerulonephritis, with the former being milder and the latter more severe, progressing rapidly and carrying a poor prognosis. The nephrotic syndrome is divided into true and false types. The true type exhibits typical clinical and laboratory features of nephrotic syndrome, including systemic edema, varying degrees of ascites, pleural and pericardial effusions, massive proteinuria, and decreased serum albumin, while globulin levels are usually normal or elevated. In contrast, the so-called false lupus nephrotic syndrome is characterized by normal or low blood cholesterol, more severe disease, and a poorer prognosis. Pathological changes in nephrotic syndrome include membranous glomerulitis or diffuse proliferative glomerulonephritis. The latter, in addition to massive proteinuria, may present with significant red blood cells and casts in the urine, impaired renal function, and hypertension. Some cases may only exhibit grade I proteinuria without any clinical signs of renal damage, with pathological changes typically being of the mesangial membranous type.
5. Cardiovascular System: Approximately 50–89% of patients exhibit cardiac symptoms, with ultrasound detection rates ranging from 36–88% and autopsy findings from 53–83%. Pericarditis is the most common manifestation, often presenting as dry fibrinous pericarditis, though effusion may also occur. Large effusions can lead to pericardial tamponade. If the pericardial layers adhere, the pericardial cavity may become obliterated, resulting in constrictive pericarditis. Patients may experience precordial discomfort, dyspnea, precordial pain, pericardial friction rub, an enlarged cardiac silhouette, or diminished heart sounds. Echocardiography has a high diagnostic yield, and LE cells may be detected in pericardial effusions.
Myocarditis is common, typically presenting with shortness of breath, precordial pain, tachycardia, diminished heart sounds, gallop rhythm, arrhythmias, and narrowed pulse pressure, progressing to cardiomegaly and potential heart failure. Electrocardiographic changes may include low voltage, ST-segment elevation, flattened or inverted T waves, and prolonged PR intervals. Some cases may be asymptomatic until triggered by certain factors, while others may be difficult to diagnose ante-mortem.
Endocarditis: Classic verrucous endocarditis (Libman-Sacks endocarditis) often coexists with pericarditis and is challenging to diagnose during life due to the subtle symptoms of parietal endocardial involvement. When the valve leaflets are affected, the mitral valve is most commonly involved, though the aortic and tricuspid valves may also be affected, leading to leaflet and papillary muscle contracture, adhesion, deformation, or chordae tendineae rupture, resulting in stenosis or insufficiency. Thrombi formed on the endocardium may embolize, and endocarditis can also predispose to infective endocarditis. Color Doppler echocardiography is the best non-invasive method for visualizing valve morphology.
Additionally, arrhythmias may occur, including atrial and ventricular premature beats, tachycardia, and varying degrees of atrioventricular block. These are primarily due to the spread of inflammation throughout the heart, affecting the atrioventricular node or bundle branches, compounded by coronary vasculitis narrowing the lumen of vessels near the sinoatrial node, atrioventricular node, and surrounding areas, leading to localized degenerative changes in the conduction system.
Approximately 50% of cases may present with arteritis and phlebitis, with thrombophlebitis of the subclavian vein being relatively common. A minority may develop coronary arteritis, often involving the left anterior descending branch, which can clinically manifest as angina pectoris due to coronary artery insufficiency. More severe coronary arteritis may lead to myocardial infarction.
In addition, some cases may present with peripheral vascular diseases such as thromboangiitis obliterans and migratory phlebitis.
6. Respiratory System Throughout the course of the disease, pleural and lung involvement occurs in 36% and 7% of cases, respectively. Pleuritis may develop, mostly dry but occasionally wet, with small or moderate effusion, occurring with similar frequency on both sides. About one-third of cases are bilateral.
The prevalence of acute lupus pneumonitis is 1–4%. Patients present with fever, dry cough, dyspnea, and occasionally hemoptysis. Hypoxemia is common. Chest X-rays show unilateral or bilateral pulmonary infiltrates, predominantly in the lower lung fields, which may be accompanied by atelectasis, diaphragmatic elevation, and pleural effusion. Chronic interstitial pneumonia may also occur, with coexisting pathological changes ranging from alveolitis to fibrosis. Radiographic features include patchy pulmonary infiltrates, often in the basal segments, which may persist for days, leading to atelectasis or even respiratory failure. Linear, reticular, or speckled shadows may also be observed. Pulmonary vasculitis can cause hemoptysis and cavitation, often complicated by lobular pneumonia, especially in the terminal stage.
7. Nervous System Symptoms often appear during the acute or terminal phase, though rarely as the initial manifestation. Various psychiatric disturbances may occur, such as agitation, hallucinations, suspicion, delusions, and obsessive thoughts. Neurological symptoms may also arise, including central nervous system involvement, commonly presenting as increased intracranial pressure, meningitis, encephalitis, cerebrovascular accidents, myelitis, or subarachnoid hemorrhage, with corresponding symptoms such as headache, nausea, vomiting, neck stiffness, convulsions, unconsciousness, hemiplegia, or paraplegia. Severe cases may be fatal. Cranial nerves may also be affected, most commonly the III, V, VI, and VII pairs, while peripheral neuropathy is rare.
8. Digestive System About 40% of cases exhibit gastrointestinal symptoms, including loss of appetite, dysphagia, nausea, vomiting, abdominal pain, diarrhea, ascites, and hematochezia. Abdominal pain may be related to peritonitis, enteritis, mesenteritis, or retroperitoneal connective tissue disorders. It is often a dull pain around the umbilicus but may resemble acute surgical abdomen in severe cases. Gastrointestinal lesions primarily result from vascular wall abnormalities.
9. Lymphoreticular System About half of the patients have localized or generalized lymphadenopathy, most commonly in the cervical and axillary regions. Enlarged lymph nodes are usually non-tender, soft, and sometimes significantly swollen, leading to misdiagnosis as subcutaneous nodules or lymphoma. Pathological examination reveals chronic nonspecific inflammation. Approximately one-third of patients have hepatomegaly, rarely leading to jaundice or cirrhosis. One-fifth of cases present with splenomegaly.
10. Hematopoietic System Anemia is common, mostly normocytic and normochromic, with IgG antibodies or complement on red blood cell surfaces. The Coombs test is positive in one-third to one-fifth of cases, indicative of autoimmune hemolytic anemia. The antibodies are warm-reactive, primarily IgG, occasionally IgM, and rarely IgA.
Leukopenia is common, typically involving granulocytes and/or lymphocytes. During active disease, both absolute and relative counts of T and B lymphocytes decrease, though the decline is less pronounced in inactive phases. The reduction in T lymphocytes correlates with disease activity and is related to impaired cellular immunity and the presence of anti-lymphocyte antibodies. Although B lymphocyte counts also decrease, functional tests often show enhanced activity.
Thrombocytopenia occurs with shortened platelet survival. Antiplatelet antibodies on the platelet surface may injure platelets when complement is activated.
11. Eyes About 20–25% of patients exhibit fundoscopic changes, including retinal hemorrhages, papilledema, and retinal exudates with oval white opacities, which are reversible lesions secondary to small vessel occlusion. Other manifestations include vitreous hemorrhage and scleritis.
SLE can overlap with other typical connective tissue diseases such as dermatomyositis, scleroderma, rheumatoid arthritis, etc., or develop sequentially. There are reports of overlap with connective tissue-related disorders like Sjögren's syndrome and Behçet's disease, and it may also coexist with other autoimmune diseases such as myasthenia gravis, Hashimoto's thyroiditis, pemphigus, and pemphigoid.
bubble_chart Auxiliary Examination
(1) Blood Routine Test As mentioned above.
(2) Erythrocyte Sedimentation Rate (ESR) Increased.
(3) Serum Protein Decreased albumin, elevated α2 and γ globulin, increased fibrinogen, and elevated cryoglobulin and cold agglutinins may occur.
(4) Immunoglobulins During the active phase, blood IgG, IgA, and IgM levels are elevated, particularly IgG. In non-active cases, the increase is insignificant or absent. Patients with prolonged and significant proteinuria may exhibit reduced blood Ig levels, while urine tests may be positive.
(5) Wind-dampness Factor Approximately 20–40% of cases are positive.
(6) Syphilis Biological False-Positive Reaction 2–15% are positive.
(7) Anti-Cardiolipin Antibodies The IgG-type positivity rate is 64%, and the IgM-type is 56%. These are closely associated with thrombosis, cutaneous vasculitis, thrombocytopenia, myocardial infarction, central nervous system disorders, and habitual late abortion or intrauterine dead fetus.
(8) LE Cells First discovered in bone marrow by Hargraves (1948), and later identified in peripheral blood by Haserick (1949). Miescher (1954) demonstrated that the lupus erythematosus (LE) cell factor is an antinuclear factor, a type of γ globulin. It is now established that four factors are required for LE cell formation: ① LE cell factor, an antinucleoprotein antibody present in peripheral blood, bone marrow, pericardial, pleural, and peritoneal effusions, blister fluid, and cerebrospinal fluid. Its corresponding antigen is a deoxyribonucleic acid-histone complex located within the cell nucleus. ② Injured or dead cell nuclei, which are not species- or organ-specific, meaning nuclei from any human or animal organ can interact with the LE cell factor. ③ Active phagocytes, typically neutrophils. ④ Complement: Required for phagocytosis. The process of LE cell formation begins with the LE cell factor interacting with injured or dead nuclei, causing nuclear swelling, loss of chromatin structure, and dissolution of the nuclear membrane, transforming it into a homogeneous, structureless mass called the "homogeneous round body." The cell membrane ruptures, releasing the homogeneous round body into the bloodstream. Multiple phagocytes aggregate to engulf this denatured nucleus, forming a flower-like cluster. Eventually, a single phagocyte engulfs the denatured nucleus, resulting in the LE cell. Complement facilitates phagocytosis.
Approximately 70–90% of active SLE patients test positive for LE cells. Other diseases, such as scleroderma and rheumatoid arthritis, may show LE cells in about 10% of cases. Additionally, chronic active hepatitis and drug rashes (e.g., procainamide or hydralazine) may also yield positive results.
(9) Antinuclear Antibody Test (ANA) This test is highly sensitive but less specific, making it suitable as a screening tool. Serum ANA is typically detected via indirect immunofluorescence using mouse liver imprints as the substrate, though Will-2 or Hep-2 cells may also be used. About 80–95% of cases test positive for ANA, particularly during active phases, with cumulative positivity rates increasing upon repeated testing. A serum ANA titer ≥1:80 is clinically significant, with titer fluctuations generally correlating with disease activity. Fluorescence patterns include peripheral, homogeneous, and speckled types, with rare nucleolar patterns. In 5–10% of cases, clinical symptoms align with SLE despite persistently negative ANA results, suggesting a possible subtype with other immunological features.
Antinuclear antibodies (ANA) encompass autoantibodies targeting various nuclear components. In SLE, the following are observed:
1. Anti-Deoxyribonucleic Acid (DNA) Antibodies These can be classified into anti-native or double-stranded DNA (n-DNA or ds-DNA) antibodies and anti-denatured or single-stranded DNA (d-DNA or ss-DNA) antibodies.
Using Crithidia luciliae, Trypanosoma equiperdum, or Trypanosoma evansi as substrates, the indirect immunofluorescence method detects anti-ds-DNA antibodies, with a positive rate as high as 93–100% during the active phase of SLE. However, the positive rate detected by radioimmunoassay is 60–70%. The peripheral fluorescence pattern of anti-ds-DNA antibodies is the most specific, indicating that patients often have renal damage and a poor prognosis. During the stage of remission, the positive rate decreases or even turns negative, and end-stage patients may also test negative. Anti-ss-DNA antibodies have poor specificity and can also be observed in other diffuse connective tissue diseases besides SLE.
2. Anti-nucleoprotein (DNP) and anti-histone antibodies: Insoluble anti-DNP antibodies, which are a type of antinuclear factor that forms LE cells—antibodies against the DNA-histone complex—exhibit a homogeneous fluorescence nuclear pattern and often appear during the active phase of SLE. Anti-histone antibodies can be detected in approximately 90% of cases of drug-induced lupus-like syndromes caused by procainamide, isoniazid, and other agents.
3. Anti-extractable nuclear antigen (ENA) antibodies: The antigen is extracted from calf or rabbit thymus and detected using agar diffusion or counterimmunoelectrophoresis. In recent years, immunoblotting has also been employed. Anti-ENA antibodies primarily include seven types, such as anti-Sm and anti-nRNP antibodies. The nRNP or U1RNP antigen is a complex of seven proteins with varying molecular weights (12-68 kDa) bound to U1RNA (where U represents uridine nucleotides), while Sm is a complex formed by the same seven proteins with U2, U1, U4, U5, and U6RNA. Anti-Sm antibodies have a positivity rate of 20–25% in SLE and are considered a marker antibody for SLE, often co-occurring with anti-dsDNA antibodies. Their presence is unrelated to disease activity but can serve as a retrospective diagnostic reference. Anti-U1RNP antibodies may appear in various connective tissue diseases. High titers, apart from occurring in SLE, are often a key serological basis for diagnosing mixed connective tissue disease.
4. Anti-Ro/SS-A and anti-La/SS-B antibodies: These are typically detected using counterimmunoelectrophoresis, though immunoblotting is also now used. The positivity rates for anti-Ro/SS-A and anti-La/SS-B antibodies are 30–39% and 13%, respectively. Both antibodies exhibit high positivity rates and significant diagnostic value in primary Sjögren’s syndrome, SLE with Sjögren’s syndrome, and subacute cutaneous lupus erythematosus. Anti-Ro/SS-A antibodies are a key serological marker for neonatal lupus and are associated with photosensitivity.
5. Anti-ribosomal P protein antibodies: Detected via immunoblotting, these antibodies have a positivity rate of about 10% and are a marker antibody for SLE.
6. Others: Literature reports that SLE patients may also test positive for anti-Ku antibodies, anti-endothelial cell antibodies, anti-neutrophil cytoplasmic antibodies, anti-neuronal antibodies, anti-laminin and anti-fibronectin antibodies, anti-type VII collagen antibodies, and anti-ganglioside antibodies. The positivity rates, specificity, and clinical relevance of these antibodies require further in-depth study.
(10) Lupus band test (LBT): Using direct immunofluorescence antibody technology, the skin immunofluorescence band or lupus band is detected as a localized immunoglobulin deposition band at the dermo-epidermal junction. The positivity rate is 92% in SLE skin lesions and 90% in DLE lesions. In SLE, normal sun-exposed skin shows a 70% positivity rate, while non-exposed skin shows 50%, but this is not observed in normal DLE skin. In chronic atrophic or hyperkeratotic lesions, the fluorescence band appears clumped; in new rashes, it appears granular or fine-linear; and in SLE normal skin, it appears speckled. This immunofluorescence band results from the deposition of Ig (mainly IgG, but also IgM and IgA) and complement at the dermo-epidermal junction.
Zeng Fanyin et al. used the 1M NaCl separation method of human skin DIF to study the lupus band in SLE patients, finding that the positive rate of this method reached 90.9%. IgG deposition was most commonly observed on the dermal side, followed by deposition on both the epidermal and dermal sides, with no cases showing deposition solely on the epidermal side. The fluorescence pattern was predominantly linear, with a few cases showing granular patterns. Recently, Zhang Xuejun et al. employed the heat-separated epidermis-dermis method in 5 cases of bullous SLE, finding that 3 cases showed vascular binding on the dermal side, while the other 2 cases exhibited binding on the dermal side, indicating antibody heterogeneity.
(11) Measurement of Cellular Immune Function Lymphocyte transformation test (PHA-LTT), old subcutaneous nodule bacillus (OT), streptococcal deoxyribonuclease and streptokinase (SD-SK) skin tests are often negative.
T-cell subset detection Using monoclonal antibody fluorescence technology, it was shown that in cases of active sexually transmitted disease, total T cells (CD3) and suppressor T lymphocytes (CD8) were significantly reduced, while the helper T cell (CD4)/suppressor T cell (CD4) (CD8) ratio increased. With treatment and stabilization of the condition, T suppressor cells returned to normal, T helper cells decreased, and their ratio returned to or fell below normal.
Natural killer cells (NK) Using the enzyme (LDH) release method to detect NK activity, results showed significantly reduced activity, which was more pronounced during the active phase.
(12) Blood moistening and tonifying body measurement About 75–90% of SLE patients have reduced blood moistening and tonifying body, especially during the active phase, with C3 and C4 being particularly affected. However, this reduction does not occur in other connective tissue diseases such as dermatomyositis, scleroderma, or rheumatoid arthritis.
(13) Circulating immune complexes (CIC) Serum CIC levels increase during the active phase.
(14) Skin tests Using autologous or homologous leukocytes for skin testing, 75% of SLE cases were positive. Using calf thymus nuclear protein for skin testing, 84% (21/25) were positive. Using calf thymus deoxyribonucleic acid for skin testing, 48% (12/25) were positive. Using calf thymus histone for skin testing, 92% (23/25) were positive.
(15) Capillary microscopy In SLE patients, diverse forms of microcirculatory disturbances can be observed in the nail folds of the fingers and the microcirculation of the tongue tip, manifested as: ① Increased microvascular loops, poor microvascular tension, and notably dilated microvessels, especially venules, with even giant vessels appearing; ② Microcirculatory flow disturbances, such as dark red blood color, static blood at the loop apex, aggregation of blood cells within the loops, slowed or stagnant flow; ③ Exudation and hemorrhage around the microvessels.
These microcirculatory disturbances lead to blood stasis and aggregation of blood cells, forming abnormal microvessels, giant microvessels, and dilated and enlarged microvessels, all of which can cause exudation and hemorrhage around the microvessels. At the same time, they can further develop into blood flow sludge, or even microthrombus formation, creating a vicious cycle.
(16) Hemorheological measurements Show significant abnormalities, such as increased whole blood viscosity, whole blood reduced viscosity, and plasma viscosity, indicating increased blood viscosity and decreased blood fluidity; prolonged red blood cell electrophoresis time, fast erythrocyte sedimentation rate, and increased K value, all consistently indicating increased red blood cell aggregation, although hematocrit is generally slightly low (anemia); increased fibrinogen in the blood and increased blood viscosity and aggregation lead to slow blood flow, providing a theoretical basis for invigorating blood and resolving stasis Chinese medicine treatment.
Since the cause of this disease is unknown, its clinical manifestations are highly variable, involving multiple tissues and organs, and the condition is complex, especially in atypical early-stage patients or those with only one or two affected organs, or those without rashes or even clinical symptoms. The currently adopted diagnostic criteria are the revised 1982 standards by the American Bi Disease Association (ARA), consisting of 11 items: ① Malar rash; ② Discoid lupus; ③ Photosensitivity; ④ Oral ulcer; ⑤ Non-erosive arthritis; ⑥ Proteinuria (>0.5g/d) or urinary cellular casts; ⑦ Seizures or psychosis; ⑧ Pleuritis or pericarditis; ⑨ Hemolytic anemia or leukopenia (<4000/mm3) or lymphopenia (<1500/mm3) or thrombocytopenia (<100000/mm3); ⑩ Anti-dsDNA antibody or anti-Sm antibody or LE cells or false-positive syphilis serology.
Meeting four or more of these criteria is required for diagnosis. The sensitivity and specificity of these diagnostic criteria both reach 96%. When combined with the lupus band test and biopsy, the diagnostic rate can be further improved.
The diagnostic criteria proposed by the Shanghai Bi Disease Society (1987) include: ⑾ Butterfly-shaped rash or discoid rash; ⑿ Photosensitivity; ⒀ Oral or nasal mucosal ulcer; ⒁ Non-deforming arthritis or polyarthralgia; ⒂ Pleuritis or pericarditis; ⑹ Seizures or psychiatric symptoms; ⒄ Proteinuria or cast urine or hematuria; ⑻ Platelets <10×109/L (100,000/mm3) or leukocytes <4×109/L (4000/mm3) or hemolytic anemia; ⑼ Positive antinuclear antibody; ⑽ Positive anti-dsDNA antibody or LE cells; ⑾ Positive anti-Sm antibody; ⑿ Decreased C3; ⒀ Positive skin lupus band test (non-lesional site) or kidney biopsy. Meeting any four of these 13 criteria can lead to a diagnosis of SLE. The sensitivity of these criteria is 95.5%, and the specificity is 96.7%, with particularly higher sensitivity for early-stage cases compared to the ARA criteria.
bubble_chart Treatment Measures
The treatment principle involves anti-inflammatory therapy to eliminate inflammation and correct pathological processes, using immunosuppressive or immunostimulatory drugs for immune regulation.
(1) Discoid Lupus Erythematosus: Treatment should be timely to prevent disfigurement and secondary carcinogenesis. Local therapy is generally used first, and systemic therapy is added if the effect is insufficient.
1. Local Therapy: ① Topical corticosteroids; ② Corticosteroids such as triamcinolone acetonide or hydrocortisone acetate suspension, injected once every 1–2 weeks for 8–10 injections; ③ Liquid nitrogen or CO2 snow cryotherapy.
2. Systemic Therapy: ① Antimalarials such as chloroquine, which has photoprotective and lysosomal membrane-stabilizing effects, as well as antiplatelet aggregation and adhesion properties. The initial oral dose is 0.25–0.5g/d, reduced after improvement; ② Thalidomide, dose 200–300mg/d; clofazimine; ③ Chinese medicinals such as modified Six-Ingredient Rehmannia Pill, Major Yin-Tonifying Pill, or Root Leaf or Flower of Common Threewingnut preparations.
(2) Subacute Cutaneous Lupus Erythematosus and Lupus Profundus: Thalidomide may be effective. Chloroquine, clofazimine, or Root Leaf or Flower of Common Threewingnut preparations can also be used. Corticosteroids may be administered if ineffective.
(3) Systemic Lupus Erythematosus:
1. For mild cases with only rash, low fever, or joint symptoms, nonsteroidal anti-inflammatory drugs (NSAIDs) such as salicylates or indomethacin may suffice. However, these drugs can sometimes injure hepatocytes, reduce glomerular filtration rate, and increase serum creatinine, requiring caution in patients with kidney disease. For prominent rashes, antimalarials like chloroquine (0.25–0.5g/d) or low-dose corticosteroids like prednisone (15–20mg/d) may be used. Thalidomide, modified Six-Ingredient Rehmannia Pill, or Root Leaf or Flower of Common Threewingnut preparations can also be administered.
2. Severe Cases:
(1) Corticosteroids: Currently the first-line treatment for severe autoimmune diseases. They significantly suppress inflammation, inhibit neutrophil migration to inflammatory sites, reduce phagocytic function of monocytes, and inhibit enzyme release. They also have antiproliferative and immunosuppressive effects, directly cytotoxic to lymphocytes, reducing NK cell numbers and IL-1/IL-2 levels, and suppressing antigen-antibody reactions.
Indications: ① Mild cases unresponsive to other therapies; ② Acute or subacute episodes with severe "toxic symptoms" such as high fever, arthralgia, weakness, and/or rapid involvement of serous membranes, heart, lungs, liver, kidneys, hematopoietic organs, or other tissues; ③ Chronic cases with clear progressive visceral damage.
Prednisone dose is approximately 0.5–1.5mg/kg daily. Mild cases may use 15–20mg/d, severe cases 40–60mg/d, and critically ill cases 60–80mg/d or even 120mg/d. Initial doses should be high, as low doses fail to control the disease promptly, risking irreversible organ damage and increasing total hormone exposure and side effects. If the initial dose is adequate, fever subsides within 12–36 hours, arthralgia disappears in 1–2 days, and toxic symptoms improve markedly. If no improvement occurs within 2 days, increase the dose by 25–100% until significant progress is observed. Besides daily dosing, alternate-day (48-hour interval) administration may be used, giving two days' dose at once on alternate mornings. Once the condition stabilizes for 1–2 weeks, gradually taper to a maintenance dose of about 5–15mg/d.
Pulse Therapy When the aforementioned dose of corticosteroids is ineffective, pulse therapy can be considered. Administer 1g of methylprednisolone diluted in 250 mL of solution for intravenous infusion over three consecutive days, followed by 100mg of prednisone daily. Rapidly taper the dose to a maintenance level within 3–4 weeks. If necessary, repeat the course after two weeks. This regimen is suitable for rapidly deteriorating cases, such as diffuse proliferative glomerulonephritis, significant neuropsychiatric symptoms, severe hemolytic anemia, and marked thrombocytopenia.
⑵ Immunosuppressive drugs: such as cyclophosphamide and azathioprine, both with a dosage of 1–4 mg per kilogram of body weight per day. The former primarily utilizes alkyl groups to bind with DNA, most notably reducing anti-DNA antibodies, decreasing DNA-anti-DNA complexes in the blood and their deposition in the kidneys. Azathioprine interferes with the synthesis of purine nucleotides, replacing the purine substrates in DNA, thereby inhibiting the synthesis of DNA and RNA. Others include chlorambucil (2 mg, 2–3 times daily), 6-mercaptopurine (50 mg, 3 times daily), and methotrexate (7.5–15 mg, taken orally once weekly). Common side effects of these drugs include leukopenia, and even bone marrow suppression, gastrointestinal disturbances, liver damage, increased susceptibility to secondary infections, long-term use may lead to infertility, teratogenesis, weakened immune function, and the development of cancer. Cyclophosphamide may cause alopecia areata and hemorrhagic cystitis, requiring cautious use.
Indications for use include: ① Ineffectiveness of corticosteroids when used alone; ② Intolerance to long-term, high-dose corticosteroid therapy; ③ To more effectively control certain lesions in SLE; ④ After acute symptoms are controlled, to further reduce the maintenance dose of hormones or to taper hormones more smoothly. These drugs are often used in combination with corticosteroids, such as in the treatment of SLE with renal damage, particularly corticosteroid-resistant nephritis. Clinical applications and animal experiments have shown that cyclophosphamide has certain efficacy in lupus nephritis regarding renal function, histopathology, and mortality. Additionally, for central nervous system lesions or acute lupus pneumonitis uncontrolled by high-dose corticosteroids, the use of such drugs may also be considered. The overall effective rate is approximately 30–50%.
In recent years, there have been significant advancements in the use of such drugs for treating SLE. Austin (1986) applied high-dose cyclophosphamide intravenous pulse therapy for refractory cases, with a dose of 0.5–1g/m2 body surface area administered monthly. Once proteinuria turned negative, the interval was extended to once every 2–3 months. Most patients showed a marked reduction in proteinuria and improved renal function after 4–6 treatments. If no improvement was observed after 9–12 treatments, the therapy was discontinued. The mechanism of action is believed to involve reducing renal tissue fibrosis, improving renal function, and preventing failure. Domestic literature has also reported the application of high-dose cyclophosphamide pulse therapy for SLE. Chen Shunle et al. treated 19 cases of refractory nephritis with monthly pulses, averaging 9 treatments per patient. Results showed that urine protein turned negative or significantly decreased in 17 cases (89.5%), and renal function improved in 9 cases. Zhang Hongkui et al. achieved favorable outcomes in 20 cases of hormone-resistant refractory lupus nephritis using long-term, intermittent intravenous high-dose cyclophosphamide (0.5–0.75g/m2 body surface area) pulse therapy (monthly for 8 sessions, then every 2 months for 3 sessions, followed by every 3 months for 3 sessions, and finally maintenance therapy every 6 months). Shi Qun et al. treated 8 lupus nephritis patients with weekly cyclophosphamide pulses of 1g intravenously. The initial dose was 400mg (administered via intravenous push with 20ml of 0.9% glucose solution), increased to 1g (via intravenous drip with 0.9% glucose solution) starting from the second week, once weekly for 4 sessions, then switched to monthly maintenance therapy, also achieving good results. Yang Xiuyan et al. explored the intervals for cyclophosphamide pulse therapy in SLE, dividing patients into three groups with 2-week, 3-week, and 4-week intervals. The dose was 15mg/kg. The 2-week and 3-week groups transitioned to monthly pulses after 10 sessions, then to once every 3 months if the condition improved. The 4-week group was treated for 6–12 months before switching to once every 3 months post-remission. The findings suggested that the pulse interval should be flexible. For severe cases, such as those with multi-system damage, neuropsychiatric involvement, or nephrotic syndrome, pulses should be administered every 2 weeks initially, with the interval extended to 3–4 weeks once the condition stabilizes.
Cyclosporin A is a new drug with immunosuppressive and immunomodulatory effects. It can interfere with the release of IL-1 and inhibit the activation of T lymphocytes. The initial dose should be 3–3.5 mg/(kg·d) (administered orally once or divided into two doses). If no improvement is observed after 4–8 weeks, the dose can be increased by 0.5–1 mg/(kg·d) at intervals of 1–2 months, with a maximum dose of 5 mg/(kg·d). It is suitable for patients who have not responded to other drug treatments.
(3) Immunostimulants: Aim to restore depressed cellular immunity, such as levamisole, thymosin, and transfer factor.
(4) Plasma exchange therapy: The principle is to attempt to remove specific autoantibodies, immune complexes, and nonspecific inflammatory mediators involved in tissue injury, such as complement, C-reactive protein, and fibrinogen. It also improves the ability of the mononuclear phagocyte system to clear circulating immune complexes. This therapy is generally used in severe cases involving multiple organ damage, ineffective hormone therapy, organic brain syndrome, pancytopenia, and active nephritis. Due to its short-lived effects, it must be combined with hormone and immunosuppressive treatments. Over 50 cases have been reported in the literature where long-term intermittent plasma exchange therapy combined with immunosuppressive therapy achieved disease remission.
(5) Dialysis and kidney transplantation: For advanced-stage kidney damage cases with renal failure, if the general condition is still stable, hemodialysis or peritoneal dialysis can be performed to remove urea nitrogen and other harmful substances from the blood, thereby improving conditions like azotemia. Kidney transplantation should be performed when extrarenal damage is inactive. Using a kidney from a relative, the 2-year survival rate is reportedly 60–65%, while using a cadaveric kidney yields a 40–45% survival rate.
(6) Traditional Chinese Medicine (TCM): Based on the combination of disease differentiation and pattern identification, this disease can be classified into types such as exuberant heat toxin, yin deficiency with deficiency, yin deficiency with yang deficiency, toxin attacking the heart, and liver depression with blood stasis for treatment. - The exuberant heat toxin type corresponds to acute and subacute cases, treated by clearing heat and removing toxin, enriching yin and cooling blood, using modified Rhinoceros Horn and Rehmannia Decoction. - The yin deficiency with blood deficiency type corresponds to grade I active cases, treated by nourishing yin and tonifying blood, cooling blood to remove toxin, using modified Anemarrhena, Phellodendron, and Rehmannia Decoction or Major Yin-Tonifying Pill. - The yin deficiency with yang deficiency type is seen in nephropathy cases, treated by enriching yin and tonifying yang, using modified Curculigo and Epimedium Decoction and Right-Restoring Decoction. - The toxin attacking the heart type is seen in cardiac involvement cases, treated by nourishing the heart and tranquilizing the mind, supplementing both qi and blood, using modified Heart-Nourishing Decoction. - The liver depression with blood stasis type is seen in hepatosplenomegaly cases, treated by soothing the liver and regulating qi, invigorating blood and resolving stasis to unblock collaterals, using modified Free Wanderer Powder.
Additionally, acupuncture therapy has certain efficacy for rashes, arthralgia, and reducing swelling. Audio-frequency electrotherapy is effective for anti-inflammation, reducing swelling, and pain relief. Preparations such as Root Leaf or Flower of Common Threewingnut, Sargentgloryvine stem, and the compound formula Jin Qiao Pian can also be used, with the former being a particularly effective anti-Bi disease drug.
Recently, bromocriptine has been used to treat SLE with some success. For active disease with severe infection, high-dose intravenous γ-globulin therapy has been attempted with good results. For aseptic femoral head necrosis, orthopedic surgery such as joint replacement arthroplasty or arthrodesis is required.
The acute type of SLE manifests with sudden onset, presenting systemic symptoms such as high fever, lack of strength, and myalgia. Facial erythema is prominent (though some cases may lack skin rashes), accompanied by severe toxic symptoms. Multiple organs are often involved, progressing rapidly to functional failure, resulting in poor prognosis. This type is now relatively rare in clinical practice. The subacute type has a gradual onset, with early manifestations mostly being nonspecific symptoms, such as fever and moderate systemic symptoms. Multiple organ damage and abnormal laboratory findings are common, and the course is recurrent and protracted, fluctuating in severity. The chronic type is characterized by discoid lesions, with an insidious onset. The pathology is mainly confined to the skin, with minimal visceral involvement, and the disease progresses slowly with a favorable prognosis.
Currently, SLE cannot be cured, but with advancements in diagnosis and treatment, the prognosis has significantly improved. Kellum and Haserick (1964) reported 299 cases, with 1-year, 5-year, and 10-year survival rates of 89%, 69%, and 54%, respectively, and a mortality rate of 38.8%. Estes and Christian (1971) followed 150 cases, reporting a 5-year survival rate of 76.9% and a mortality rate of 36%. By the 1970s, Dubois reported survival rates rising to 96%, 67%, and 57%. Ginzler (1982) documented survival rates of 91%, 77%, and 71%, while Aigswaak (1989) reported a 10-year survival rate as high as 87%. Chen Shunle et al. conducted a 10-year follow-up of 50 SLE cases, calculating survival rates from the time of diagnosis: 1-year, 5-year, and 10-year survival rates were 98%, 86%, and 76%, respectively. Huashan Hospital of Shanghai Medical University followed 566 SLE patients over 32 years, calculating survival rates from the time of disease onset: overall 1-year, 5-year, and 10-year survival rates were 93%, 73%, and 60%, respectively. Patients diagnosed after the 1980s had significantly higher survival rates compared to those from the 1950s and 1960s. Among 752 hospitalized SLE cases over 23 years (1958–1980), the mortality rate was 16.22%, with the highest mortality occurring within the first 3 years of disease onset and declining thereafter. Deaths due to SLE itself accounted for 48.18%, with uremia being the leading cause, followed by heart failure and central nervous system lesions. Deaths from complications accounted for 51.82%, higher than those from direct disease effects, with secondary infections, bacterial pneumonia, and sepsis being the most common causes. Baum and Ziff reported that SLE patients exhibited significantly lower antibody responses to Brucella antigen injections compared to controls. Additionally, defects in phagocytic function, reduced leukocyte chemotaxis, presence of lymphocytotoxic serum factors, impaired delayed-type hypersensitivity, and selective cellular immune deficiencies have been documented, leading to poorer resistance against bacterial and fungal infections. The use of corticosteroids also affects the body's resistance to infections, with the duration and dose of corticosteroids showing a linear relationship with infection rates. When the prednisone dose exceeds 30mg daily, the infection rate rises sharply. Furthermore, blood urea nitrogen levels exceeding 21.4 mmol/L can suppress humoral and delayed hypersensitivity responses, increasing susceptibility to infections. Corticosteroids themselves can also cause upper gastrointestinal bleeding and perforation, leading to death.
Moreover, early symptoms of SLE can vary widely, especially in cases without skin lesions, making misdiagnosis common. With advances in immunological diagnostic techniques and heightened clinical awareness, early diagnosis and appropriate treatment have become possible, undoubtedly improving survival rates in the future.
1. Cultivate an optimistic attitude, correctly face the disease, build confidence in overcoming it, maintain a regular lifestyle, balance work and rest, take appropriate breaks, and prevent infections.
2. Eliminate various triggers, including all possible internal medications and chronic infection sites, and avoid irritating topical drugs and all external stimuli.
3. Avoid excessive exposure to sunlight and ultraviolet rays, especially during active periods. If necessary, apply sun-protective medications such as 3% quinine ointment, compound titanium dioxide ointment, or 15% para-aminobenzoic acid ointment. Other factors like cold and excessive X-ray exposure can also worsen the condition and should not be overlooked.
4. Use hydralazine, procaine, penicillamine, antibiotics, and sulfonamides rationally.
5. Patients should practice birth control and avoid pregnancy during active periods. If there is kidney damage or multi-system damage, early therapeutic late abortion should be considered.
