Advances in the treatment of keloid by intradermal injection

Keloid is a pathological scar characterized by hyperplasia and aggressive growth of connective tissue of the skin.It is formed after traumatic, inflammation, operation more, good hair is in the place such as before bosom, scapular ministry, earlobe.Keloids on exposed parts affect aesthetic appearance, skin lesions in functional areas affect local activities, and keloids are often accompanied by pruritus, pain, local hypersensitivity, etc., causing heavy psychological burden on patients, and in severe cases, the quality of life is affected.Although keloid has a variety of clinical treatment methods, its formation mechanism is still unclear and the recurrence rate is high, so it is a difficult problem for surgical treatment.Intra-dermal injection has been widely used in the treatment of keloid at home and abroad.

Keloids are benign tumors of the dermis and subcutaneous tissue that result from excessive collagen deposition after tissue damage.In the early stage of trauma, inflammatory reactions occur in the tissue dermis, leukocyte infiltration, excessive proliferation, activation and migration of fibroblasts, excessive deposition and disorder of collagen fibers in the extracellular matrix are the pathological basis for keloid formation.In recent years, the combination of traditional methods and new treatment methods for keloid has achieved a certain degree of efficacy.Intradermal injection for keloid is widely used at home and abroad because of its simple operation, remarkable effect and few adverse reactions.The research progress on the mechanism of drug action and injection method of intradermal injection for keloid is summarized as follows.

1. Injectable medicines

1.1 Corticosteroid hormone

Topical injection of corticosteroids is one of the most common and effective methods.Prednisolone acetate, triamcinolone acetate and compound betamethasone are commonly used in clinical practice.Hormones can inhibit the expression of type I and III procollagen genes in fibroblasts, reduce the synthesis of collagen fibers, accelerate the degradation of collagen, and reduce the content of hyaluronic acid. In addition, hormones can reduce the release of histamine and other inflammatory mediators, and reduce the intensity of allergic reactions.Corticosteroids are divided into short-acting preparations and long-acting preparations, so there is a difference in the injection cycle in skin lesions. Prednisolone acetate is injected once a week, no more than 2 ~ 3mL each time.Triamcinolone acetonide acetate should be injected once every 2 to 3 weeks.Compound betamethasone is injected once every 3 to 4 weeks, no more than 1mL each time.Topical injection of corticosteroid is often used in combination with other drugs. The dosage of corticosteroid is not clearly prescribed, which needs further study.The common adverse reactions of local injection of corticosteroid hormones include local skin and subcutaneous tissue atrophy, pigmentation, telangiectasia, secondary infection, tissue necrosis, etc.

1.2 Antitumor drug

Antitumor drugs were earlier used in the treatment of keloid.Clinical commonly used anti-tumor drugs are 5-fluorouracil (5-fu) and bleomycin.Anti-tumor drugs act competitively on the synthesis of DNA and RNA, thereby inhibiting the proliferation of fibroblasts, reducing the production and secretion of collagen, and achieving the purpose of treating scars.5-fu is commonly used in foreign countries at a dose of 40mg/mL ~ 50mg/mL, while in domestic clinical treatment, the low dose of 5mg/mL ~ 10mg/mL combined with lidocaine injection has a difference in efficacy and adverse reactions. Therefore, the drug dose and injection interval and treatment course need to be further studied.Because 5-fu is a cell-cycle specific drug, 5-fu alone has an obvious therapeutic effect. However, studies at home and abroad have shown that 5-fu combined with hormone drugs is more effective than alone, and has the advantages of low recurrence rate and fewer adverse reactions.Adverse reactions to injection of anti-tumor drugs include pain, erythema swelling, pigmentation and skin atrophy.

1.3 Calcium Channel Blockers

Calcium channel blockers are mainly used in the treatment of cardiovascular diseases. In recent years, they have been used in the treatment of keloid and achieved good results.Commonly used calcium channel blockers are verapamil and nicardipine.Calcium channel blockers inhibit fibroblasts, thereby reducing collagen content in scars and reducing extracellular matrix synthesis.Studies have shown that verapamil may inhibit the synthesis of -smamrna and extracellular matrix in urethral scar fibroblasts induced by TGF- 1 by enhancing the expression of Smad7, inhibit interleukin-6, intravascular cell growth factor, and induce apoptosis.Verapamil (2.5mg/mL) was injected according to the size of the lesion, with an injection volume of 0.5 ~ 2.0mL for each site, and the total amount was no more than 10mg each time. The injection was given every 4 weeks, and the curative effect was observed, until the volume became smaller and the hardness became soft, so as to relieve the patient’s itching, pain and other symptoms, and achieve the treatment purpose.Studies have shown that verapamil is superior to triamcinolone in terms of inducing apoptosis and adverse drug reactions.Adverse reactions include pain, heart rate changes, and hypotension.So bradycardia, conduction block, asthma, should be banned in pregnant women.

1.4 Interferon

Interferon is widely used in clinical antiviral and immunomodulation, and has achieved certain curative effect in anti-fibrosis in recent years.Interferon can be used to treat keloid by local injection and topical ointment.Interferon is divided into -(leukocyte) type, -(fibroblast) type, -(lymphocyte) type.Currently, INF -2b and INF are mainly used in the treatment of keloid.INF -2b is a naturally occurring cytokine that inhibits fibroblast proliferation and biosynthesis, inhibits TGF- 1 expression, but does not induce fibroblast apoptosis and is therefore prone to relapse.INF -2b(1.5 million U/mL) should be injected into the lesion at a distance greater than 2cm.Inf-gamma can promote the production of collagenase by fibroblasts in vitro, promote the decomposition of collagen, soften keloid, reduce the volume, and achieve the purpose of treatment.Inf-gamma injection to keloid the general dosage for each injection of 1 ~ 3 million U, once a week, for 10 weeks.Common adverse reactions to interferon injections include headache, muscle soreness, and flu-like symptoms.

1.5 Botulinum toxin A

Botulinum toxin type A is the bacterial endotoxin secreted by botulinum toxin. It mainly ACTS on the neural-muscle junctions and inhibits the release of acetylcholine, thereby reducing the tension of the skin.Botulinum toxin A is A safe and effective treatment that can affect cell proliferation and apoptosis, treat keloid and prevent disease recurrence.Wang Lin et al. found that botulinum toxin type A (50U/mL) with A spacing of 1cm, 5U/ point and A total amount of no more than 100U per person had A significant effect on improving intractable keloid pain and itching after treatment.Currently, there are four types of botulinum toxin type A preparations registered.Serious adverse reactions have not been reported in the treatment of keloid with botulinum toxin type A injection, but there may be unexpected potential adverse reactions. Problems such as injection dose, treatment course, discontinuation period after treatment and recurrence after discontinuation need to be solved.

2. Injection therapy application

2.1 Combined application

Triamcinolone acetonide and 5-fu are commonly used in combination therapy in clinical practice. The combination of the two drugs can play a synergistic role, and the treatment efficiency can be significantly improved.Bijlard et al. found that the combined use of 5FU and triamcinolone acetonide was more effective than the single use of 5FU or triamcinolone acetonide, and the effective rate of patients with local combined injection of the two drugs was 50% ~ 90%.Yao quan et al. verified the efficacy and safety of the combined application of triamcinolone acetonide and 5-fu with the meta method, but the relationship between the proportion of triamcinolone acetonide and the therapeutic efficacy and adverse reactions should be improved through long-term follow-up and experimental studies.Combined injection of steroid hormones and anti-tumor drugs will produce obvious pain, so the injection should be added with 2% lidocaine to reduce pain, and reduce the concentration of the two drugs, reduce direct stimulation to the injection site, reduce toxic and side effects.Existing studies have shown that the effect of intradermal injection with lidocaine has been studied, and it has been found that the pain is not alleviated after the local injection with lidocaine, and the occurrence of adverse reactions caused by the use of lidocaine is reduced naturally by not using lidocaine.Drugs injected into skin lesions can also be combined with surgery, laser, cryotherapy and radiotherapy, with good efficacy and low recurrence rate.

2.2 Use of syringes

Strictly adhere to the principle of aseptic operation, with iodine volts tampons disinfection vitiligo patches, the use of disposable syringe treatment, on the edge of the keloids and tapered to the leather into the needle, back to the drawing without blood after injected into the skin, slowly into the needle and medicine to keep the needle injection in scar tissue, injection to scar tissue surface slightly pale, not injected the drug into the normal skin, or scarring, lest cause adverse reactions.For those with larger scars, multi-point injections can be used to minimize the number of needle points.Currently, needleless syringe is used in clinical practice, that is, high pressure gas is generated through the power source without needle during drug injection, so that the drug liquid forms a fine liquid flow, which penetrates the skin and reaches the subcutaneous immediately. Because of the change of injection principle, the drug liquid disperses and distributes under the skin, the effective time is faster, and the drug absorption rate is higher.It has been reported that the use of needle-free syringe can make the drug enter the injection site in the form of mist diffusion, increase the absorption area and improve the absorption rate, and there is no obvious stinging sensation compared with the traditional needle-free syringe.The use of needleless syringe can improve the uneven effect of traditional syringe drugs and the pain of patients during treatment.

3. Summary

Intra-dermal injection therapy is widely used in clinical practice, with simple operation, remarkable effect and acceptable cost.Because inject method, inject interval, inject dosage, the effect of different treatment that treats course of treatment, the adverse reaction after treating also has difference.Intra-dermal injection therapy can flatten and soften keloids, but it cannot completely remove keloids or reduce the area of scar tissue.Clinically, the treatment method should be considered according to the location, size, shape, age, the patient’s opinion, financial capacity and other factors of keloid.Now keloid formation mechanism is lack of full understanding, and there is no standardized radical treatment program, clinical often adopt comprehensive treatment methods to alleviate symptoms, reduce the recurrence rate.Therefore, the study of the pathogenesis of keloid, the improvement of existing treatment methods and the development of new treatment programs should continue.

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