Lupus is an autoimmune disease that can involve all systems of the body. Patients with lupus often talk about “lupus”, but it is a life-threatening disease after all, and the 5-year survival rate is very low if it is not treated actively. I have been fighting side by side with my “lupus” friends for nearly 30 years and have gained a lot. I have received a lot of thank-you letters from my “lupus” friends (the largest proportion of the patients who wrote to me) and have drawn a lot of experiences for the taste and reference of my patients and peers.
Experience 1 Lupus is a chronic disease, which is more dangerous and complicated, and should be treated in regular hospitals.
Lupus can involve any organ of the body, especially the kidney, central nervous system and blood system, etc. It is easy to be misdiagnosed and mistreated, so patients with lupus should go to regular hospitals with rheumatology and immunology departments. Many small clinics or “miracle men” often mislead patients, giving them the names of “ancestral”, “traditional Chinese medicine” and “eradication”. The patients are often misled by small clinics or “miracle men” under the names of “ancestral”, “traditional Chinese medicine” and “eradication of root causes”, and stop using all the medicines prescribed by regular hospitals and use only “secret recipes”, which cost a lot of money and have little effect, and also delay the best treatment period, eventually leading to the death of the patients, and similar cases abound. Here, we declare that the condition of lupus is complicated and changeable, and some unexpected problems often occur, which require multidisciplinary joint treatment, especially the consultation and treatment by rheumatologists. Many medications cannot be stopped casually, including hormones and hydroxychloroquine.
Experience 2: Keeping lupus patients in a happy mood can help the success of treatment.
According to my observation, lupus patients tend to be very good, often very successful in their careers and studies, and they mostly have typical lupus personalities, such as sentimental, demanding perfection and love to take the bull by the horns, and if you look at their palms, you will know that they are a very worried person. These personality traits have some correlation with the onset of the disease. Therefore, once you get lupus, you need to get out of the world, don’t be demanding and keep your mood happy. Listen to nostalgic music or Christian hymns, which will make the patient feel very calm and relaxed.
Experience 3: Choose the right medication according to the severity of the patient’s clinical manifestation
Generally speaking, for those who do not have any organ involvement and only have manifestations such as arthritis, rash, fever and weakness, only hormones, hydroxychloroquine and/or methotrexate and/or thalidomide are sufficient, and the oral hormone dose is often moderate [0, 5mg/(kg, d)]. If one or more important organs are involved, the oral hormone dose is often higher, requiring more than 1 mg/(kg, d) of prednisone, perhaps short-term shock therapy with hormone and immunoglobulin, and a combination of immunosuppressive therapy, including cyclophosphamide, mycophenolate, cyclosporine, tacrolimus, azathioprine, or leflunomide, etc. The main drugs used in the induction of remission period are, first line Cyclophosphamide or mycophenolate, cyclosporine, tacrolimus or leflunomide in the second line, and rituximab (melphalan) in the third line. First-line agents for maintenance consolidation are mainly azathioprine or mycophenolate. Of all the above drugs, hormones and hydroxychloroquine should be the basis of treatment for all patients with lupus and should generally not be easily discontinued unless serious irreversible adverse effects occur.
Experience 4. The choice of immunosuppressants is an art
1. The most selected immunosuppressants for lupus treatment are cyclophosphamide and mycophenolate lipid, and the regimen is adjusted only after 6 months of induction therapy (unless the disease deteriorates significantly at 3 months), and can be interchanged with each other when the efficacy is poor. Mycophenolate should be preferred in patients of younger age, with subsequent reproductive requirements, mild hepatic and renal insufficiency, and modest economic circumstances, with the main advantage of similar efficacy to cyclophosphamide shock, but with less hepatic and renal toxicity, bone marrow suppression, amenorrhea, alopecia, and severe infection, and reversal of renal vascularization. Although mycophenolate does not cause amenorrhea in patients and can maintain fertility, it is teratogenic to the fetus and is discontinued for at least 6 weeks prior to conception (this is the shortest discontinuation time of any marketed immunosuppressant). It is worth noting that the dose used for mycophenolate esters in the national population should not be as high as in foreign countries and should be limited to 2 grams per day. Cyclophosphamide shock should be chosen for patients who are older, have had children, have no reproductive requirements, and are in a poor financial situation. The EULAR regimen of cyclophosphamide shock in small doses (0,4 to 0,6 g every 2 weeks) is preferred because of similar efficacy to the NIH regimen of high-dose cyclophosphamide shock (0,8 to 1,0 g once a month), and the occurrence of infections, amenorrhea, and gastrointestinal reactions less. However, regardless of the regimen, it is advisable to have liver function, blood and urine tests before the next shock for early detection of possible side effects such as hepatotoxicity, bone marrow suppression, hemorrhagic cystitis and cystic fibrosis. For severe lupus (acute lupus nephritis, lupus encephalopathy, etc.), for rapid control of the disease, cyclophosphamide can be 0,2g intravenously once every other day or 0,4~0,6g once a week while the hormone shock is closely monitored for side effects. If the above regimen is not effective for 7-10 weeks, treatment should be changed. To prevent tumors and cystic fibrosis that may occur with long-term cyclophosphamide use, the total duration of cyclophosphamide use is mostly controlled to six months or a total dose of 12 g or less, with subsequent switching to other drugs or at least lengthening the interval of treatment. The toxicity of cyclophosphamide in causing amenorrhea is a growing concern, with women around 30 years of age likely to suffer the most damage (8 g cumulative is the risk dose), with the risk dose increasing by 1 g for each year of age and decreasing by 1 g for each 2-year increase in age. To protect ovarian function, pseudo-menopausal therapy can be used, with leuprolide 3, 75 mg (half the dose for weight <50 kg) injected subcutaneously or intramuscularly every 4 weeks for 3-6 months, starting 2 weeks before the use of cyclophosphamide (not used at the same time as cyclophosphamide, otherwise it causes ovarian damage).
Leflunomide can also be used for lupus patients with joint symptoms and nephritis: Leflunomide is less likely than cyclophosphamide to induce menstrual irregularities and gastrointestinal reactions, but there is still some liver damage, decreased white blood cells, increased blood pressure and decreased body weight.
3. For lupus nephritis type V or lupus with predominantly reduced platelets, cyclosporine A or tacrolimus can be used. The biggest advantages of cyclosporine A and tacrolimus are less bone marrow suppression and low probability of fetal teratogenesis during pregnancy. Cyclosporine A is less potent, but has a slightly greater potential to induce hypertension, gingival hyperplasia, hyperuricemia and renal damage, while Tacrolimus is more potent and also has a risk of inducing renal damage and high blood glucose, but has fewer other side effects. Both drugs are not selected when renal function is abnormal or when renal pathology has thrombotic vascular disease (thickened endothelium and increased blood pressure). During use, it is best to closely monitor the blood concentration.
4. Azathioprine can be used for the maintenance and consolidation of lupus with reproductive requirements and prominent interstitial renal lesions. The greatest advantage of azathioprine is low fetal teratogenicity and low tumor induction, but there is a risk of liver damage and severe myelosuppression, which can be effectively avoided if the genetic polymorphism of functional mercaptopurine methyltransferase (TPMT) is detected in advance and the drug and drug dose are selected according to the metabolism of this enzyme.
Experience V. Short-term multi-target therapy for patients with severe lupus in order to obtain rapid results
The treatment regimen combining multiple immunosuppressive agents is divided into two main types.
(1) cyclophosphamide-centered: combined with methotrexate or mycophenolate or raphenazole or leflunomide or FK506 or cyclosporine A or azathioprine or melphalan.
(2) Mycophenolate centered in combination with FK506 or cyclosporine A or rapheoside or leflunomide or melphalan. However, mycophenolate is not combined with azathioprine, as both block purine synthesis, and cyclosporine A is not combined with FK506, both are neurocalciferol inhibitors, which are inhibitors of early T-cell activation.
Experience 6: Lupus combined with thrombocytopenia should be treated according to certain procedures
1. First of all, we should exclude the secondary thrombotic thrombocytopenic purpura, because this disease is more dangerous and differs greatly from the treatment of platelet reduction due to other causes. When patients have bleeding, microvascular hemolytic anemia, neuropsychiatric symptoms, fever and renal damage, there are moderate to severe anemia, elevated reticulocytes, increased plasma free hemoglobin, nucleated erythrocytes and erythrocytes visible in blood film, and erythrocyte fragments in bone marrow. If there is a moderate to severe anemia, elevated reticulocytes, increased plasma free hemoglobin, nucleated erythrocytes and erythrocyte debris in blood film, compensatory hyperplasia of red and macronuclei in bone marrow, but the coagulation test is basically normal, Coomb’s test is negative and ADAMTS13 is severely reduced, then secondary thrombotic thrombocytopenic purpura should be considered and plasma exchange and plasma transfusion are preferred. 2, to see if there is a combination of viral infection, especially cytomegalovirus infection: if the patient has fever, high transaminases, decreased neutrophils and increased atypical lymphocytes, tests such as MCV-PP65 antigen and TORCH-IgM need to be done, once the cytomegalovirus infection is confirmed, the hormone dose is not increased but decreased, while adding ganciclovir and immunoglobulin. 3. Exclude possible medication factors, many antibiotics and heparin may lead to lower platelets, discontinue them in time. 4. Once it is determined that lupus itself is causing the thrombocytopenia, a typing test should be performed to distinguish between Th2/B cells (humoral immunity, Th2 cells producing IL-4, IL-5 and IL-10) or Th1 cells (cellular immunity, producing IFN-γ, TNF-α, IL-2 and IL-3, etc.) mediated immune thrombocytopenia or both. If elevated gamma-interferon and interleukin-2 in blood and elevated CD4+IFN-γ+ double positive T cells by flow cytometry are examined, this suggests Th1 cell-mediated immune thrombocytopenia, which can be treated with anti-thymocyte globulin, mycophenolate, tacrolimus or fludarabine; if elevated anti-erythrocyte, leukocyte and platelet antibodies are examined or CD5+CD20+CD19+ B1 B-cell ratio or IL-4+CD4+ double-positive T-cell ratio, suggesting Th2/B-cell-mediated immune hemocytopenia, treatment with hormones, immunoglobulins, cyclophosphamide or melphalan (total efficiency about 80%) or vincristine (1-2mg/w) may be indicated. Whichever of the above mechanisms causes thrombocytopenia, consolidation therapy with cyclosporine 3~5mg/kg, d (effective after 2~3 weeks) is required after disease control. The efficacy of using glucocorticoids combined with gammaglobulin is better than glucocorticoids or gammaglobulin alone, and the time required for platelets to return to normal is shorter. Immunoglobulin can rapidly elevate the platelet count, but cannot treat the root cause of thrombocytopenia; the effect lasts for 3-4 weeks and requires other drugs to maintain the efficacy. Other methods such as Danazol 400-800mg/d (increased after 2-12 weeks), hydroxychloroquine, splenectomy or autologous hematopoietic stem cell transplantation can also be used. For those with life-threatening severe recalcitrant thrombocytopenia platelet growth factors can be used, which include recombinant human interleukin 11 (megakaryocyte granules), recombinant human thrombopoietin and thrombopoietin receptor agonists [Romiplostim and Eltrombopag].
Lesson 7: Lupus pregnancy must require taking medications, not stopping them.
Pregnancy in lupus patients must be stable for at least 6 months with lupus and a creatinine clearance of 50 ml/min or more, preferably evaluated by rheumatology and obstetrics and gynecology at least every 4 weeks. To prevent relapse, hydroxychloroquine and/or low-dose hormones must be used. abortion is recommended for relapse in early pregnancy, whereas for relapse in mid- to late pregnancy, hormone doses may be increased and azathioprine or tacrolimus or cyclosporine A, which are less toxic to the fetus, may be used. to prevent the risk of preeclampsia, low-dose aspirin may be added. With established antiphospholipid syndrome, a prophylactic dose or therapeutic dose of low molecular heparin is also indicated.
Lesson 8: Anticoagulants and ACEI and/or ARB analogues should be considered for persistent proteinuria with inactive disease
Because many studies have found that persistent urinary protein may be associated with intra-glomerular thrombosis, especially when there has been nephrotic syndrome with albumin <20g/L and persistent antiphospholipid antibodies, aspirin and low-molecular heparin are needed. ACEI and/or ARB can improve glomerular function and help reduce urinary protein. When the 24-hour urinary protein is above 0,5g, ACEI/ARB can reduce urinary protein leakage by 30% and significantly slow down the progression of nephropathy. In certain patients with recalcitrant urine protein, the use of herbal medicines such as Radix et Rhizoma, Astragalus or Flavin capsules can help reduce urine protein.
Experience 9: Adjuvant medication for lupus should not be ignored
1. Osteoporosis: osteoporosis is prone to occur during the course of medication, and the following points should be noted: quit smoking; avoid excessive caffeine intake and excessive alcohol consumption; increase food with high calcium content; exercise appropriately; avoid falls; check bone density regularly, usually once every six months to a year, and add anti-osteoporosis drugs once bone density decreases. The first two are oral medications, which need to be taken on an empty stomach with more water and in an upright position to prevent esophagitis caused by staying in the esophagus, and the latter is an intravenous medication, which is used only once a year and is more suitable for patients who usually do not have time to visit the clinic. of osteoporosis. In addition, there is a drug to promote bone formation parathyroid hormone fragment, severe osteoporosis can be considered for use.
2, hyperlipidemia: when LDL exceeds 2, 58 mmol/L (100mg/dl)], in order to stop atherosclerosis, make statin-type lipid-lowering drugs.
3, excessive sweating: hormone-induced hyperhidrosis using Liu Wei Di Huang Wan, persistent sweating more use Yu Ping Feng San.
4, rash: topical use of Xiliotuo or tacrolimus or Yuzor, while taking oral hydroxychloroquine + reaction stop + tretinoin (2 tablets/day), taking Chinese herbal medicine antelope horn is effective.
5, pulmonary fibrosis: use Jin Shui Bao, Bai Ling capsule or acetylcysteine or pifidone.
6. Immunocompromised: Patients with lupus using hormones and immunosuppressants for more than half a year should have their immune function checked, and if they are immunocompromised, they should consider taking placenta or nuclear cheese oral solution, which is better for preventing infection.