An introduction to the diagnosis and treatment ideas of vasculitis Cutaneous vasculitis refers to a group of inflammatory diseases occurring in the blood vessels of the skin, the etiology of which is complex and often closely related to type III allergic reactions. In addition to skin manifestations, most of them are accompanied by systemic damage at the same time. It is a group of diseases worthy of attention and research by dermatologists. First, before treatment should be made as far as possible to make a clear clinical diagnosis of the disease cutaneous vasculitis is a group of diseases, each kind of vasculitis clinical manifestations, pathogenesis, treatment programs and prognosis, although there are some similarities, but more is different. Such as cutaneous vasculitis, although the clinical manifestations of a variety of, but some kinds of lesions have certain characteristics, such as white atrophic lesions deeper, mainly occurring in the ankle, after the healing of the white atrophic spots; allergic purpura, chronic pigmented purpura lesions superficial, mostly in the lower limbs, the former manifestation of petechiae or petechiae, and the latter rash seems to be the size of the tip of a needle, peppercorns scattered or densely distributed; nodular vasculitis and Nodular polyarteritis mainly invades the deep dermis and subcutaneous small and medium-sized arteries, most of the lesions are asymmetrical in distribution, generally unilateral, even if bilateral, the lesions are heavy on one side and light on the other; on the contrary, erythema nodosum and allergic vasculitis lesions are very symmetrical; cryoglobulinemia vasculitis is often accompanied by necrosis of the fingers (toes), Raynaud’s phenomenon, thrombosis, such as superficial migratory thrombophlebitis, antiphospholipid antibody syndrome The coexistence of pustules and vasculitis on histopathology is necessary for the diagnosis of pustular vasculitis; paraneoplastic vasculitis is seen in lymphoproliferative diseases, mainly palpable purpura, urticaria-like vasculitis and persistent elevated erythema are more common; lymphomatous granulomatosis mainly invades the lungs, skin, and the nervous system, and the most common manifestations include cough, dyspnea, and chest pain; in addition, combined with the internal organs and systemic damage and simple skin vasculitis, the most common manifestations are the combination of the lungs, skin and nervous system damage and the combination of the skin vasculitis. In addition, the prognosis for combined visceral damage and cutaneous vasculitis alone varies greatly, as does the choice of therapeutic regimen. Therefore, a well-trained dermatologist should take advantage of the specialties and strengths of the skin specialty to analyze and identify the skin lesions, combined with the dermatopathological changes and other relevant experimental tests, to make a definitive diagnosis as far as possible, and then choose the appropriate treatment plan, and carry out regular treatment and follow-up. Although the types of drugs used in the treatment of vasculitis are not complicated, the view that the so-called misdiagnosis is not the wrong treatment is not desirable for dermatologists. Second, pay attention to the interconnection between pathological changes and clinical manifestations Although the pathological changes of cutaneous vasculitis have obvious characteristics, it is difficult to make an accurate clinical diagnosis without combining the clinical manifestations, and the results will inevitably affect the follow-up treatment. It should be noted that the pathologic changes of vasculitis are vasculocentric inflammation, and perivascular and peritubular infiltrates should not be mistaken for vasculitis. Skin vasculitis has two main histopathologic changes, 1, leukocyte-crushing vasculitis, such as allergic dermal vasculitis, urticarial vasculitis, persistent bullous erythema, anaphylactic purpura, nodular polyarteritis, and white atrophy. 2. Lymphocytic sexual vasculitis, such as chronic pigmented purpuric dermatosis. The two types of vasculitis may suggest two different pathogenetic mechanisms, suggesting that the leukocytoclastic type may represent immunity mediated by immune complexes whereas the lymphocytic type is an immune response associated with cellular immunity. In addition the depth of vascular lesions and the size of the invading vessels in cutaneous vasculitis are important for clinical diagnosis. Such as allergic vasculitis, urticarial vasculitis, persistent elevated erythema, allergic purpura and white atrophy, skin histopathologic changes are small vasculitis in the upper and middle parts of the dermis; chronic pigmented purpura pathology shows changes in the superficial layer of the dermis capillary vasculitis; nodular polyarteritis (dermatologic type), nodular vasculitis, mainly violating the deeper part of the dermis and the small and medium-sized arteritis of the subcutaneous tissue. There is no doubt that the complexity of the clinical manifestations of cutaneous vasculitis and the depth of vascular lesions, the size of the infringing vessels have a direct relationship. For example, nodular polyarteritis, due to the depth of the lesion, the skin lesions are often not very obvious in the early stage, except for the most common ones, such as fever, weakness and severe pain. Therefore, more should be done from the clinical point of view, combined with pathological changes and related auxiliary examination, to arrive at a more certain diagnosis early. Third, an accurate understanding of the signs of vascular injury and laboratory evaluation The main signs of vascular endothelial cell injury are: (1) circulating endothelial cells (CEC): is considered to be the only in vivo at present can be specific and directly reflect the markers and indicators of vascular endothelial cell injury. (2) Coagulation factor VIII (F Ⅷ ): Its increased activity helps to differentiate necrotizing vasculitis of large and medium-sized vessels from small vessel disease. It correlates with disease activity and can be elevated several-fold in systemic vasculitis such as polyarteritis nodosa and Wegener’s granulomatosis, and decline when treatment is effective. (3) vW factor (vWF): plasma vWF levels are markedly elevated in patients with cutaneous vasculitis, but there is no significant relationship between this and the severity of vasculitis. (4) Anti-neutrophil cytoplasmic antibodies (ANCA) have high sensitivity and specificity in the diagnosis of Wegener’s granulomatosis, multiple microarteritis, and some necrotizing vasculitis. It has been recognized that ANCA, a group of autoantibodies directed against neutrophil cytoplasmic antigens, has a marked specificity for Wegener’s granulomas, and it is believed that ANCA is a serologic marker for the above diseases. (5) AECA (anti-vascular endothelial cell antibody): It is most commonly seen in Wegener’s granulomatosis, polyarteritis nodosa, micropolyarteritis, and temporal arteritis, etc. AECA-positive secondary vasculitides are necrotizing vasculitides in SLE, RA, and overlap syndromes. Laboratory evaluation is clinically important in patients with vasculitis, with the goal of helping to determine the underlying etiology, or potentially associated lesions; some reports have suggested that tests for coagulation and components of the anticoagulation system are helpful in monitoring the activity of vasculitis in the setting of lupus erythematosus. Cryoglobulins, rheumatoid factor, and complement should be examined in all patients presenting with allergic vasculitis. AECA (anti-vascular endothelial cell antibodies) can be used as an indicator of disease activity and prognosis in systemic vasculitis. For example, in Wegener’s granulomatosis, polyarteritis nodosa, micropolyarteritis, and temporal arteritis, immunosuppressant dosage reduction in patients in remission must be cautious if AECA is persistently positive. If AECA and ANCA are persistently negative, this indicates a low likelihood of disease recurrence. Complex internal interactions between circulating plasma protein components, blood cells and platelets, and endothelial cells determine the type of cutaneous vascular pathology. Cutaneous vascular diseases associated with abnormal plasma protein factors can be categorized as: vasculitic, thrombotic, hemorrhagic, proliferative, and degenerative, and usually present with several alterations that can overlap or transform each other. Fourth, familiarize with and understand the existing classification methods and trends of vasculitis Skin vasculitis classification methods, although there is no perfect classification method, but as a dermatologist should be familiar with and understand as much as possible. (1) according to the etiology of classification can be divided into primary and secondary, the causative factors directly acting on the vascular wall caused by the person called primary vasculitis, etiology is often unknown; by the neighboring tissues inflammatory lesions spreading to the vascular wall caused by the person called secondary vasculitis, there is often a clear etiology, such as a variety of infections or secondary to lupus erythematosus and other systemic diseases; (2) according to the pathogenesis of the classification of non-immune and immune, such as Neisseria infections, Tuberculosis, syphilis, herpes virus direct infection of non-immune vasculitis. For example, infection-induced immune complex vasculitis, immunoglobulin-mediated lupus vasculitis, cryoglobulinemic vasculitis, malignant tumor-related vasculitis, and drug-induced immune-injurious vasculitis, etc.: (3) According to the systemic involvement or lack of it, it can be divided into cutaneous and systemic. If only the skin or mucous membranes are involved, it is known as cutaneous vasculitis or non-systemic vasculitis. When internal organs are involved, symptoms and signs of corresponding organs or tissues may appear, which is called systemic vasculitis. Systemic vasculitis and non-systemic vasculitis are often difficult to distinguish; (4) according to the pathological characteristics of the acute inflammatory phase is divided into exudative degenerative, necrotic and proliferation-oriented granulomatous; according to the main infiltrating cells are divided into neutrophilic, lymphocytic and histiocytic. Moreover, these factors may overlap in the pathogenesis, resulting in different names being used for the same disease and the same name being used for different types of disease. The future development trend of ideal classification of vasculitis should take into account the clinical symptoms, involved tissues and organs, the nature and diameter size of the blood vessels involved, as well as the pathophysiological mechanism of vasculitis and histopathology, immunopathology and other characteristics, so as to make the clinical diagnosis and treatment more clinically meaningful. Fifth, pay attention to the classification of vasculitis patients and follow-up management Usually, according to the severity of the disease and organ involvement, the treatment will be roughly according to the classification of mild, moderate, severe and systemic vasculitis, and at the same time, it is also necessary to combine the etiology and pathophysiology of different vasculitides to choose a different treatment plan. At the same time, because vasculitis is easy to recur, most patients need intermediate treatment, so patient follow-up treatment is particularly important. 1.General treatment: first of all, the possible causes should be removed, including allergenic substances or chemicals, infections or other factors. If bacterial infection is suspected, effective antibiotics can be chosen. If chronic diseases such as diabetes mellitus exist at the same time, appropriate treatment measures should be taken actively. Symptomatic supportive treatment should also be given, such as NSAIDs for pain. Attention should be paid to rest, occur in the lower limbs of the patient to elevate the lower limbs, avoid cold stimulation and wear tight clothing. 2, mild vasculitis: only limited skin damage, mild systemic symptoms. On the basis of general treatment, the following 1-3 kinds of drugs can be selected according to the condition, alone or in combination. These therapeutic drugs include ① Amphetamine sulfone: anti-inflammatory effect and a certain immunosuppressive effect, the initial 25mg-50mg / d, and then gradually increase the dose. ②Reglan: its immunosuppressive effect may be one of the main mechanisms for the treatment of vasculitis. It has good efficacy, low relapse rate, and is still effective when used after relapse. The dosage is usually 20mg, 3 times a day, and the dosage is gradually reduced after the condition has stabilized for 1 week; ③ hydroxychloroquine: it can achieve anti-inflammatory effect by inhibiting the release of lysosomal enzymes, reducing the synthesis of inflammatory mediators and inhibiting the chemotaxis of neutrophils, etc. The dosage is 200mg, 2 times a day. The dosage is 200mg twice a day, and the course of treatment should not be less than 4 weeks. ④ Dipyridamole: Improve microcirculation through vasodilatation, antiplatelet aggregation and 5-hydroxytryptamine release, and antithrombotic effects. The dose is usually 25 mg 3 times daily. ⑤ Hexetone Cocaine: improves microcirculation and reduces blood viscosity. The dose is usually 400mg twice daily. (6) Non-steroidal anti-inflammatory drugs: such as indomethacin, can inhibit the synthesis of prostaglandin E2 and other inflammatory mediators, and has strong anti-inflammatory and analgesic function. The dose is usually 25mg-50mg, 2-3 times a day. (7) Thalidomide: Stabilizes lysosomal membrane and inhibits inflammation, and inhibits neutrophil chemotaxis, immunomodulation and anti-Langerhans cell proliferation. The dose is usually 25mg twice daily. 3, moderate and severe vasculitis: recurrent episodes, skin lesions with blisters, ulcers, nodules and other manifestations, can be accompanied by systemic symptoms. Usually on the basis of the treatment program for mild vasculitis. Glucocorticoids: the first choice for most moderate to severe vasculitis, depending on the severity of the disease, prednisone 20mg-40mg, daily dose. After the rash subsides and the condition stabilizes for a week, the dosage should be gradually reduced. ②Immunosuppressive drugs: including methotrexate 5mg-20mg per week for adults, divided into 3 times; azathioprine: the dosage depends on the level of thiopurine methyltransferase (TPMT), the daily dose of 0.5mg-5mg/kg; cyclosporine A twice a day, 5mg-5.0mg/kg, divided into 2 times orally; cyclophosphamide 500mg-2g/kg per day, orally. When using immunosuppressive drugs, attention should be paid to bone marrow suppression, secondary infection and liver and kidney function and other important organ function damage. Involvement of internal organs exists in patients with systemic vasculitis, and sometimes the function of organs is seriously affected due to persistent damage, and even life-threatening. Protection of organ function should be prioritized in treatment, which is also the key to reducing the morbidity and mortality rate. Attention should be paid to the prevention of toxic reactions to drugs and immunosuppression secondary infections in the treatment. On the basis of moderate or severe vasculitis, it is advocated to combine glucocorticoid and immunosuppressant. 4.Other treatments ① Enzyme phenolate (MMF) is a selective inhibitor of hypoxanthine nucleotide dehydrogenase (IMP-DH), which mainly inhibits the proliferation of activated T and B lymphocytes, so its immunosuppressive effect has a certain degree of selectivity. In recent years, it has been tried to be used in the treatment of various vasculitis. ② Tumor necrosis factor (TNF-α) inhibitors such as Inasept can be used in cases of refractory vasculitis and have become a new option for the treatment of vasculitis. (iii) Anti-CD20 antibody rituximab (rituximab) is a humanized anti-CD20 monoclonal antibody that binds specifically to the surface antigen CD20 of human B-cells or B-lymphoma cells, and discovers a cytotoxic effect mediated by complement-dependent cytotoxicity (CD-CC) and antibody-dependent cell-mediated cytotoxicity (ADCC), thereby inducing destruction of B-cells or B lymphoma cells and suppressing the immune response.