How Effective Is Methotrexate for Psoriasis?

Arthritis-type psoriasis is a disease. Arthritis psoriasis (psoriatic psoriasis) accounts for about 2% of psoriasis. It occurs in women and often occurs after chronic psoriasis vulgaris. It can also be caused by recurrent symptoms. In addition to the typical skin symptoms of psoriasis, it can also be accompanied by joint lesions. Although most occur in patients with diagnosed active skin disease, some patients (especially children) have joint disease before psoriasis. The degree of skin damage in psoriasis is not related to the occurrence of arthritis, but people who have a family history of spondyloarthropathy and widespread pitting and concave changes in the finger / toenail are at risk of developing psoriatic arthritis increase. The genetic correlation of psoriatic arthritis is heterogeneous.

Arthritis psoriasis

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Arthritis-type psoriasis is a disease. Arthritis psoriasis (psoriatic psoriasis) accounts for about 2% of psoriasis. It occurs in women and often occurs after chronic psoriasis vulgaris. It can also be caused by recurrent symptoms. In addition to the typical skin symptoms of psoriasis, it can also be accompanied by joint lesions. Although most occur in patients with diagnosed active skin disease, some patients (especially children) have joint disease before psoriasis. The degree of skin damage in psoriasis is not related to the occurrence of arthritis, but people who have a family history of spondyloarthropathy and widespread pitting and concave changes in the finger / toenail are at risk of developing psoriatic arthritis increase. The genetic correlation of psoriatic arthritis is heterogeneous.

Chinese name

Arthritis psoriasis

Alias

Arthritis psoriasis

Symptom

With joint disease

Causes

Heredity, infection, metabolic disorders, etc.

Arthritis psoriasis (psoriatic psoriasis) accounts for about 2% of psoriasis. It occurs in women and often occurs after chronic psoriasis vulgaris. It can also be caused by recurrent symptoms. In addition to the typical skin symptoms of psoriasis, it can also be accompanied by joint lesions. Although most occur in patients with diagnosed active skin disease, some patients (especially children) have joint disease before psoriasis. The degree of skin damage in psoriasis is not related to the occurrence of arthritis, but people who have a family history of spondyloarthropathy and widespread pitting and concave changes in the finger / toenail are at risk of developing psoriatic arthritis increase. The genetic correlation of psoriatic arthritis is heterogeneous.

(I) Causes of the disease The etiology of this disease varies, and there are mainly theories of inheritance, infection, metabolic disorders, endocrine effects, neuropsychological factors, and immune disorders.
1. Genetic factors The disease often has a tendency to gather in families. The prevalence of first-degree family members is as high as 30%, and the risk of single egg twins is 72%. Domestic reports of family history are 10% to 23.8%, foreign reports of 10% to 80%, generally considered about 30%. The disease is an autosomal dominant inheritance with incomplete penetrance, but some people think it is an autosomal recessive or sex linked inheritance.
2. Infectious factors (1) Viral infection: Some people have performed antiviral treatment on patients with psoriasis accompanied by viral infection, and as a result, the condition of psoriatic arthritis also eased.
(2) Streptococcal infection: It is reported that about 6% of patients have a history of pharyngeal infection and upper respiratory symptoms, and their anti- "O" titer is also increased.
(3) Metabolic disorders: Some people think that the metabolic disorders of fat, protein and sugar have pathogenic effects on this disease, and some people think that the metabolic abnormalities of these three substances are secondary findings, and some people think that this disease is related to the three major substances. Metabolic disorders have nothing to do.
(4) The role of endocrine dysfunction in psoriasis and endocrine gland function has long attracted people's attention.
(5) Neuropsychiatric disorders: Previous literature often reports that mental factors are related to the disease. For example, trauma can sometimes cause the disease to worsen or worsen the condition, and it is believed that this is due to increased vascular motor nerve tension after mental stimulation. However, during the Patriotic War of the former Soviet Union, the number of people with severe trauma was particularly high, but the incidence of this disease was not increased.
(II) Pathogenesis 1. Henseler et al. Proposed to classify psoriasis as a type 2 genotype (60% is autosomal dominant inheritance). The age of onset is young, with an average age of 22 years for men and 16 years for women. The course of the disease is irregular and can be general. The HLA-CW6 positive rate is as high as 85% (relative risk 4.5). 50% of patients with this type have psoriasis in their father or mother. Type is sporadic, and the peak age of onset is 60 years. 15% of patients are related to HLA-CW6 (relative risk is 7.3). Parents of this type of patients do not have this disease. Recent research suggests that HLA is closely related to the clinical type of psoriatic arthritis. For example, asymmetric peripheral arthritis is related to HLA-B38, B17, B13, CW6, etc., and spondylitis is related to B27 or B39. It was also found that the earlier occurrence of arthritis was related to HLA-DR4 and DRW53, the severity of the disease was related to DQW3, and the narrowing and erosion of joint space was related to HLA-A9 and B5.
2. Some people have confirmed the existence of eosinophilic inclusions in the spinal nucleus, but others have denied the existence of such inclusions. Although there seems to be some basis for the pathogenic effects of viral infections, no specific virus causing the disease has yet been isolated. Toddler patients often have a history of acute tonsillitis or upper respiratory tract infection, and the symptoms are relieved after penicillin treatment and tonsillectomy. All these indicate that the infectious factors have a pathogenic effect on the disease.
3. It has been reported that two types of oxaloacetate dehydrogenase combined with coenzyme are lacking in the skin lesions of patients with this disease. These two enzymes are related to skin maturation and keratinization. It has also been found that lactate dehydrogenase and cytochrome oxidase activities in patients' blood are increased, and succinate dehydrogenase is decreased. The changes in these enzymes are not necessarily primary or secondary, but they certainly have an effect on sugar metabolism. Studies have found that patients with a lack of cyclic adenosine monophosphate within the skin lesions. Epidermal proliferation and division are caused by a lack of cyclic adenosine monophosphate. Cyclic adenosine also activates phosphorylase, which can affect sugar metabolism. If the content of adenosine monophosphate in the epidermis is reduced, the glycogen content is increased, the mitosis of the epidermal cells is enhanced, and the conversion rate is accelerated. Normal epidermal cell conversion time is 4 weeks, while psoriasis conversion time can be shortened to 3 to 4 days, which indicates that the reduction of cyclic adenosine monophosphate content in skin lesions has a certain pathogenic effect.
4.Farber pointed out that about one third of patients can alleviate psoriasis during pregnancy, and the condition worsens after delivery. Some people in China have also reported good results in treating this disease with pregnancy urine. Some patients may also develop pituitary-adrenal dysfunction. Urinary 17-ketosteroids are reduced. Clinical treatment with glucocorticoids can achieve better results.
5. Pathology (1) Skin pathology: According to the characteristics of skin lesions, they are generally divided into common type, pustular type and erythrodermic type.
Ordinary type: the epidermis changes earlier, and there are keratinous hyperplasia in the epidermal layer, mainly keratosis. Keratinocytes can be combined into flakes, which are filled with air and refracted, so they are silvery white scales. During quiescence, hyperkeratosis may be more pronounced than incomplete keratosis. In the stratum corneum or below the stratum corneum, small abscesses composed of neutrophils are sometimes seen. This line of neutrophils is caused by the capillaries of the upper layer of the dermal papillae migrating to the surface. It is more common in early damage and rarely Found in obsolete sexual damage. The granular layer becomes thinner or disappears, the spinous layer becomes thicker, with the extension of the epidermal process, and the end is often thickened, which can sometimes connect with the adjacent epidermal process. There can be obvious intercellular edema in the spinal cell layer at the top of the nipple. In early skin lesions, neutrophils and lymphocytes are scattered in the spinal cell layer. Capillary blood vessels in the upper dermis are dilated and tortuous, and the tube wall is slightly thickened with mild to moderate inflammatory cell infiltration in the stroma. In old lesions, the infiltration is composed of lymphocytes and plasma cells. Plasma cell infiltration is most prominent in the papillary portion. The papillary portion can be extended upwards with edema and often extends to the surface keratinized layer. The top spinous cell layer becomes thinner, and only 2 to 3 layers of cells remain. There are often no granule cells, so it is easier to scrape small blood vessels at the top of the nipple and cause clinical spotting bleeding. Due to the extension and widening of the epidermal process, the dermal papilla also grows and narrows accordingly, and is rod-shaped or finger-shaped.
Pustular type: The pathological changes are basically the same as the common type, but large pustules can be seen in the stratum corneum, and the vesicles are mainly neutrophils. The thickness of the spinous cell layer and the change of rod-shaped nipples were not obvious. The dermal layer has more severe inflammatory infiltration, mainly lymphocytes, histiocytes, and a small amount of neutrophils.
Red skin disease type: Except for the pathological features of psoriasis, other changes are similar to dermatitis, showing significant keratosis, thinning and disappearing of the granular layer, hypertrophy of the spinal cell layer, prolongation of epidermal processes, and obvious intracellular and extracellular Edema, but no blister formation. Edema in the upper dermis, vasodilation and congestion, lymphocytes and neutrophils infiltration around the blood vessels, and eosinophils are sometimes seen. Late infiltration is mostly lymphocytes, histiocytes, and plasma cells.
(2) Arthritis pathology: It is basically similar to rheumatoid arthritis, but lacks the typical rheumatoid arthritis. Synovial edema and hyperemia may be present at an early stage, and then synovial cells are slightly proliferated and villi are formed. Lymphocytes and plasma cells infiltrate around the synovial vessels. In the course of the disease, fibroblasts proliferated and synovial fibrosis occurred. Typical changes are caused by (toe) osteolysis, non-inflammatory proliferation of mesangial membrane and intermittent loss of cortical bone. At the same time, it may be accompanied by mild new bone formation caused by enhanced osteoblast activity, but the entire process is mainly osteolytic, and the metatarsophalangeal joint of the foot is obvious.

(I) Treatment 1. Western medicine treatment:
(1) Non-steroidal anti-inflammatory drugs have a faster anti-inflammatory and analgesic effect, are effective for most psoriatic arthritis, and are the drugs of choice. Commonly used are aspirin, ibuprofen, indomethacin, non-prazazone, diclofenac, asimicin, and sulindac, etc. An oral can be selected according to the patient's tolerance, clinical efficacy and economic conditions.
(2) Cytotoxic drugs: Because the disease has excessive proliferation of epidermal cells in the pathology of skin tissue, certain cytotoxic drugs that inhibit DNA synthesis can be used to inhibit mitosis of cells for therapeutic purposes. Although these drugs have a certain effect on the disease, they will produce toxic reactions and are easy to relapse after stopping the drug. During the medication, liver, kidney function and white blood cells should be checked frequently, and indications should be strictly selected.
Methotrexate: It is a derivative of methotrexate, which has a good effect on psoriasis, but the poisoning dose and therapeutic dose of the drug are very close, the safety range is narrow, and it can cause extensive liver fibrosis. Indications should be strictly selected during use. The drug is suitable for erythrodermic, pustular and extensive skin lesions, and its contraindication is the same as that of aminopterin sodium (Bai Xue Ning). Do not use drugs such as sulfa, salicylic acid, tetracycline family, aminobenzoic acid, and phenytoin during medication. Because methotrexate is attached to plasma proteins, it can be replaced by the aforementioned drugs, which interferes with its excretion in the renal tubules, thereby increasing its toxicity. Can be taken orally, intramuscularly or intravenously at a dose of 20 to 25 mg per week, or 2.5 mg per day, for 5 days, 2 days after withdrawal, 5 days after withdrawal, and 7 days after withdrawal. Weinstein based on the principle of epidermal cell dynamics, proposed to take 2.5-7.5 mg orally every 12 hours, three times a day, and then administer the same method every week. The reason is that the cycle of normal epidermal cells is 457 hours, while the cycle of epidermal cells in this disease is only 37.5 hours. The drug is mainly used in the DNA synthesis phase of the cell cycle, which can prevent DNA synthesis and inhibit mitosis of cells. After taking the medicine for 12 to 16 hours after taking it once, taking it 3 times in a row can inhibit all the diseased epidermis within 36 to 48 hours. This is also the principle of action on joint diseased tissue cells. Normal epidermal cells have fewer side effects because they have a long cell cycle and enter the DNA synthesis phase.
Other immunosuppressive agents such as azathioprine, hydroxyurea, thiopurine, and cyclosporine A are effective and should be selected and used according to their respective advantages and disadvantages.
Retinoic acid (retinoic acid) This medicine is effective for psoriatic skin lesions and arthritis. All-trans retinoic acid has a good effect, and it is 0.5Mg / kg each time. This medicine has teratogenic effects. It is contraindicated in pregnant and lactating women. It is best not to use in patients with liver and kidney dysfunction.
Ethimide is commonly used among them. Although it is effective, it has the effect of inducing leukemia, so it should not be used again.
(3) Glucocorticoids: At present, it is generally not advisable to take such drugs, because their side effects are large, and a rebound phenomenon may occur after reduction or withdrawal.
2. Non-pharmacological treatment (1) Photochemotherapy: oral methoxsaline (8-methoxypsoralen), 2 hours after exposure to long-wave ultraviolet rays, the effect is better for psoriasis skin lesions, and arthritis symptoms have been reported Can be reduced accordingly.
(2) Physical therapy: short-wave electrotherapy, ultrasound therapy, whole-body mineral hot water bathing method, whole-body steam bath method.
(3) Anesthesia: stellate ganglion block, knuckle joint synovial injection therapy, sacroiliac joint synovial injection therapy, knee joint synovial injection therapy.
(4) Other treatments: psychotherapy and surgical arthroplasty.
(B) the prognosis of this disease is long, can last for decades, can even be extended for life, easy to relapse. Patients with psoriasis generally have a better prognosis. A few patients have extensive joint involvement, severe skin lesions, and high disability rates. Acute disease arthritis itself rarely causes death, but glucocorticoids and cytotoxic drugs can cause fatal complications such as severe infections, peptic ulcers and perforations.