RU2214249C2 - Method for treatment of chronic hyperplastic laryngitis - Google Patents

Abstract

FIELD: medicine, otorhynolaryngology. SUBSTANCE: invention proposes method for treatment of chronic hypertrophic laryngitis by direct administration of an intralaryngeal interferon inductor poludanum and cycloferon in vocal folds or subfolding space. Method provides high concentration of preparation in inflammation focus and rapid voice recovery. EFFECT: improved treatment method.

Description

 The invention relates to medicine, in particular to otorhinolaryngology, and is intended for the treatment of recurrent chronic hyperplastic laryngitis. It can be used in the clinical practice of otorhinolaryngologists and phoniatrists.

 The urgency of the problem of chronic hyperplastic laryngitis is due to its prevalence. According to various authors, it makes up from 8.4 to 10% of the inflammatory pathology of the larynx (V.S. Kuznetsov 1965, 1972; A.I. Alimov 1973; O.K. Kleinsasser 1965, 1969).

 In recent years, there has been an increase in recurrent viral infections. The deterioration of the environmental situation in the country, allergization, and the spread of tobacco smoking, including passive smoking, lead to a weakening of general and local immunity. Good vascularization of the mucous membrane of the larynx and upper respiratory tract creates additional conditions for the reproduction of the virus in the area of the primary focus.

 Reproduction of the viruses of the mucous membrane of the larynx consists of several stages. The speed of reproduction depends on the general and local reactivity of the body, the functional state of the organs of the upper respiratory tract.

 At later stages of the development of infection, the epithelium grows, desquamates, loosens the larynx mucosa. All of the above leads to its defects and metaplasia, creates favorable conditions for the occurrence of co-infection.

 In 25 patients with chronic laryngitis with grade II-III epithelial dysplasia, we identified Epstein-Barr virus (EBV) by means of a biopsy test and polymerase chain reaction (PCR). This virus belongs to the group of herpes viruses, is extremely widespread throughout the world and is interesting, mainly due to its possible role in the development of carcinogenesis (Fields B., Naipa D. 1989).

 As our observations have shown, the clinical manifestations of chronic laryngitis not only depended on the presence of EBV virus in the mucous membrane of the larynx, but also caused specific specific forms of the disease, characterized by a persistent long course and resistance to all types of drug and surgical treatment.

 A known method of treating patients with inflammatory and benign hyperplastic formations of the larynx, including microsurgical intervention, antibiotic therapy and physiotherapy (copyright certificate 468632, MKI A 61/06).

 Treatment with this method has several disadvantages, the main of which are relapses of the disease and, as a result, poor voice quality due to the development of cicatricial changes in the mucous membrane of the vocal folds. Sclerosis of the mucous membrane of the vocal folds is caused by both frequent inflammatory changes and inadequate surgical interventions - biopsies. As a result, the chronic inflammatory process of the mucous membrane in some cases leads to malignancy.

 In 1999, we proposed a method for the treatment of chronic hyperplastic laryngitis, including endolaryngeal microsurgical intervention and anti-relapse systemic treatment with one of the interferon inducers, amiksin, to avoid relapse and prevent malignancy (copyright certificate 2144331).

 The disadvantage of this method is the low concentration of the interferon inducer in the focus of inflammation and, as a result, an increase in the duration of treatment (taking the drug up to six weeks). The inexpediency of using endolaryngeal microsurgical intervention in patients with submandibular laryngitis complicated by compensated stenosis of the larynx. The inability to use amixin in patients with severe pathology of the kidneys, liver and blood diseases.

 These disadvantages can be prevented using the proposed method of treatment.

 The aim of the method is to increase the effectiveness of the treatment of chronic hyperplastic laryngitis and the prevention of relapse of the disease.

 The goal is achieved by an integrated approach to diagnostic issues and the use of a new local method of introducing interferon inducers (cycloferon, half-dan, ridostin, larifan, etc.).

 The theoretical prerequisite for the development of the method was the study of interferon status, morphological studies, microbiological data and clinical observations.

 The study of interferon status (INF) was carried out by us in 25 patients with chronic hyperplastic viral laryngitis before treatment. All patients showed a decrease in titers of interferon α from 40 to 320 units / ml and interferon γ from 4 to 16 units / ml. Spontaneous production of interferon was not determined, only 6 patients showed an increase to 4 units / ml. In some cases, a high titer of serum interferon was noted with a sharp decrease in the production of γ INF, which indicated immunodeficiency of the T-cell link.

 Currently, the main focus of PCR use remains the diagnosis of infectious diseases. Unlike enzyme-linked immunosorbent assay, which is widely used for such purposes, DNA and RNA diagnostics can detect the causative agent of the disease in the blood, tissues and other body fluids. For the differential diagnosis of chronic inflammatory processes, PCR is widely used in gynecology, urology, pulmonology and dermatology. In otorhinolaryngological practice, this method has not yet found proper application.

 Epstein-Barr virus was detected in 25 patients. Basically, this virus was associated with mycoplasmas and fungi, which predetermined the search for a new effective method of treating this pathology.

 According to the proposal, a method of treating chronic hyperplastic laryngitis includes local injection of a solution of an interferon inducer into the region of the vocal folds or into the region of the inflammatory infiltrate of the lining of the larynx, which allows creating a high concentration of the drug in the affected area.

 Of the interferon inducers in the treatment of patients with chronic viral laryngitis, we first proposed the use of half-dan and cycloferon.

 The active substance is a half-dan - a complex of polyadenylic and polyuridylic acids (in equimolar ratios). Half-moon is a high molecular weight inducer of interferon. Stimulates the formation of α-, β- and γ-interferons. It enhances the activity of natural killers, the level of which is initially reduced in patients with herpes virus infection. It is a modulator of the immune system - it increases the performance of T- and B-cell immunity and macrophage-phagocytic system. It has a pronounced inhibitory effect on herpes viruses, eliminates immunosuppression. The advantages of this drug is that in therapeutic doses it is not toxic, does not have allergenicity and pyrogenicity. Reduces the frequency of exacerbation in chronic viral recurrent diseases. It is well compatible with antibiotics and other drugs for the treatment of viral and intracellular infections (Ershov F.I. 1986).

 For the treatment of chronic laryngitis, half-dandelion is used in injections. 200 μg lyophilized powder is dissolved in 4 ml of 0.5% sol. novocaine. The introduction is carried out 1 time every 2 days. The duration of treatment is 7-10 injections. The number of patients 12.

 Cycloferon is a low molecular weight inducer of the synthesis of alpha, beta and gamma interferons in the body. It is a synthetic analogue of the natural alkoloid from the Citrus grandis culture. Cycloferon in the body stimulates the production of interferons by immunocompetent cells - leukocytib macrophages, fibroblasts, as well as epithelial cells. Cycloferon contributes to the correction of the body's immune status.

 Treatment of chronic hyperplastic laryngitis with cycloferon is carried out in the form of injections of 250 mg. The introduction is carried out 1 time per day after 2 days. The basic course is 5-10 injections. The number of patients 13.

Case Study
For intralaryngeal administration of half-dan, the contents of the ampoule or vial (200 μg of powder) ex tempos are dissolved in 4 ml of 0.5% sol. novocaine and injected in 2.0 ml (100 μg) in each vocal fold or subglottic space every other day. The course of treatment is prescribed 7-10 injections.

 For the intralaryngeal administration of cycloferon, one ampoule with a capacity of 2 ml containing 250 mg of the drug substance is used. 1 ml is injected into each vocal fold or subglottic space after 1-2 days, depending on the patient's individual tolerance. 5-10 injections are prescribed for the course of treatment.

The technique of intralaryngeal administration of the drug is as follows. The skin of the front surface of the neck at the injection site is treated with 70 ^o spiritus vini aetilici. The prepared solution is filled into a disposable 5 ml syringe. Injection is performed on both sides laterally and below the anterior notch of the thyroid cartilage in men by 3-3.5 cm; in women, 2-2.5 cm. With sub-folding laryngitis, this distance increases by 0.7-1.0 cm. It is also necessary to ensure that the patient is sitting without tension, motionless, since even a slight movement can interfere with the administration of the drug directly into the focus inflammation. In the first few hours after the injection, pain is possible.

 Patient Bashmakova T.M. 1950 born medical history 946/99 was hospitalized with a diagnosis of chronic sub-laryngitis laryngitis acute stage, compensated stenosis of the larynx.

 Complaints of hoarseness, rapid fatigue of the voice, shortness of breath during physical exertion. Sick for 5 years, last exacerbation for 1 month. I do not smoke. She received antibiotic therapy, antihistamines, inhalations of hydrocortisone and a 1% solution of dioxidine 15. The treatment was ineffective.

 Objectively - the voice is hoarse, with laryngoscopy pronounced sub-fold rollers. The mucous membrane of the vocal folds and subglottis is hyperemic, swollen. When breathing, the glottis in the posterior third of 0.5 cm.

 In the study of INF status, the insufficiency of the interferon system of the III degree in α and γ link.

 Given the presence of compensated stenosis of the larynx and, as a consequence, the impossibility of carrying out a biopsy test, the patient made scraping of the mucous membrane of the under-skin space. During PCR, the Epstein-Barr virus was detected.

 Since July 1999, taking into account the prevalence of the patient’s process, a course of intralaryngeal injections of the hemisphere has been started. On the second day after the first injection, the patient noted a decrease in hoarseness, she began to breathe better. After 4 weeks, the patient almost recovered a normal sonorous voice, significantly decreased spanning infiltrates and inflammatory changes.

 In the control study of interferon status - insufficiency of the interferon system of the 1st degree in the link and the 2nd degree in the γ-link.

 Patient Tarnovsky L.B. B. 1939 medical history 1922/99 was treated with a diagnosis of chronic hyperplastic laryngitis, stage of exacerbation. Chronical bronchitis.

 Complaints of hoarseness, sore throat. Sick for 15 years, last exacerbation for 2 months. Smokes for 29 years on a pack of cigarettes per day. He received antibiotic therapy, antihistamines, inhalations of hydrocortisone and a 1% solution of dioxidine 15. The treatment was ineffective.

 Objectively - the voice is hoarse, with laryngoscopy, the vocal folds are hyperemic, there is swelling along the free edge of the right and left vocal folds. Over the entire surface of the vocal folds there is a cobweb-like whitish coating (leukoplakia). With microlaryngoscopy, the thickening of the epithelium in the area of the vocal folds, the epithelium looks gray-red, the skin is similar, the sites of keratinization of the epithelium in the form of surface white spots are determined.

 In the study of INF status, the insufficiency of the 1st degree interferon system in α and γ link.

 June 4, 1999, given the prevalence of the process, the patient underwent decortication of the vocal folds. During PCR diagnosis, the Epstein-Barr virus was detected. A month later, the patient began to receive intralarengial injections of cycloferon. After 2 weeks, the patient returned to a normal sonorous voice, after 3 weeks the laryngoscopic and microlaryngoscopic picture returned to normal.

 In the control study of IFS - INF indicators are within normal limits.

Using the proposed method provides the following advantages:
- allows you to create a high concentration of the drug in the focus of inflammation;
- good functional effect (sonorous voice);
- prevents relapse of the disease (observation period up to 3 years);
- the listed advantages together provide a faster recovery and avoid malignancy of tissues;
- the use of intralaryngial administration of an interferon inducer is a conservative and at the same time effective way of treating chronic sub-laryngitis.

Sources of information
1. Ershov F.I. The interferon system is normal and with pathology. - M .: Medicine, 1996 .-- 239 p.

 2. Kuznetsov B.C., Egorov A.A. Some ways to improve the organization of phoniatric care // Krat. thesis. reports of the 3rd Congress of Otorhinolaryngologists of the RSFSR. - Rostov n / a. - 1972. - S. 192-194.

 3. Fields B., Nipe D. et al. Virology. - M .: Mir, 1989 .-- 494 p.

 4. Kleinsasser O. Mikrolaryngoskopie und endolaryngeale Mikrochirurgie. -Technik und Typische Befimd. Stuttgart - New York, 1968. - 180 s.

 5. Kleinsasser 0. Mikrolaryngoskopie und endolaryngeale Mikrochirurgie. // HNO. - 1974. - Bd. 22. - 2.- S.33-38.

Claims (1)

 A method for the treatment of chronic hypertrophic laryngitis by intralaringeal administration of an interferon inducer - half-dan and cycloferon, characterized in that the drug is injected directly into the vocal folds or the subglottic space.