RU2796387C1 - Method of herpes zoster treatment - Google Patents

Abstract

FIELD: medicine; infectious diseases.

SUBSTANCE: invention is intended for the treatment of herpes zoster infection. The method includes administering acyclovir orally, from the first day of admission to the hospital, at a dosage of 800 mg 5 times a day for 10 days, and local treatment of the skin lesion with a solution of aniline dye once a day from the first day of admission to the hospital until the end of the eruptive period. Additionally, Superlymph 25 IU is prescribed in the form of suppositories rectally 2 times a day for 10 days.

EFFECT: method provides prolongation of the interrecurrent period, elimination of cases of postherpetic neuralgia, helps to increase the effectiveness of therapy, reduces the time of regression of clinical manifestations, such as the duration of the period of rashes, allodynia, insomnia, the severity of pain syndrome, reduces the area of skin lesions, the incidence of bacterial superinfection due to the use in combination with basic, etiotropic and pathogenetic therapy of Superlymph.

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Description

The method relates to medicine, namely to infectious diseases, is intended to reduce the duration of clinical manifestations of herpes zoster infection, improve the results of treatment of this infection.

The increase in the number of patients with herpes zoster observed in recent years is associated with an increase in its severe and complicated forms. Complications include the development of postherpetic neuralgia, which often leads to a significant decrease in the quality of life, and sometimes to early disability [Immunomodulators in the treatment of herpes zoster / Provotorov V.Ya., Bibicheva T.V., Popov V.E., Rogova Yu .A., Kharahordina Yu.E. // Actual problems of medicine. T. 26-1, no. 11 (182), 2014. - S. 54-56].

The main schemes of antiviral therapy for herpes zoster in adult patients are: valaciclovir 1000 mg 3 times / day. orally for 7 days or famciclovir 500 mg 3 times / day. orally for 7 days, or acyclovir 800 mg 5 times / day. orally for 7-10 days [Complex treatment of herpetic lesions of the peripheral nervous system / Igonina I.A., Kolokolov O.V., Bakulev A.L., Kravchenya S.S., Kolokolova A.M., Sitkali I.V. // RMJ. 2013. No. 30 No. - p. 15-18; Dyudyun A.D. General principles of diagnosis and treatment of patients with herpesvirus infection (clinical lecture). Dermatovenereology. Cosmetology. Sexopathology. 2016, No. 1-4. - S. 118-155].

Numerous studies have proven the effectiveness of Superlymph in patients with herpes infection. The antiviral effect of Superlymph is due not only to the direct inhibitory effect of the drug on the replication of the herpes virus, but also indirectly through the activation of cytotoxic effector cells, such as macrophages, natural killers, and others, which also occurs as a result of the action of cytokines.

The immunotropic drug Superlymph was developed at the Department of Immunology of the Russian National Research Medical University. N.I. Pirogov. The drug, which is a standardized complex of antimicrobial peptides and cytokines, has antiviral and antimicrobial effects, stimulates the functional activity of phagocytic cells, such as monocytes and neutrophils: activates phagocytosis, the production of cytokines: IL-1, TNF, induces antitumor cytotoxicity of macrophages, increases the activity of natural killers [found on the Internet https://www.vidal.ru/drugs/superlymph_30595]. In the available literature, we did not find indications of the effectiveness of the use of Superlymph in patients with herpes zoster.

The invention according to patent RU No. 2770293 "Method of treating recurrent bacterial vaginosis in women infected with the herpes simplex virus" contains a treatment regimen using Superlymph for the treatment of recurrent bacterial vaginosis associated with herpes infection. The method includes a two-stage therapy. At stage 1, antibiotic therapy with clindamycin 300 mg 2 times a day for 7 days after meals, starting from the 7th day of the menstrual cycle, is carried out, and at stage 2, immunomodulatory therapy with Superlymph 10 IU is carried out, one suppository vaginally at night for 10 days. The course of immunomodulatory therapy is repeated after 2 months. The use of the invention makes it possible to achieve a reduction in the frequency of recurrence of bacterial vaginosis in women of reproductive age infected with the herpes simplex virus, correction and normalization of the microbial flora, prolongation of remission and minimization of the frequency of complications due to the normalization of the biocenosis of the urogenital tract, sanitation of the focus, and a decrease in the level of pro- and inflammatory cytokines in the cervical mucus. However, this study addresses the treatment of bacterial vaginosis associated with herpes simplex, but does not address the treatment of herpes zoster infection.

A known method for the treatment of postherpetic neuralgia in elderly patients with organic personality disorders [US Pat. RU No. 2285528 dated 10/20/2006]. The authors propose to carry out complex treatment with antiviral agents, immunomodulators, analgesics, nootropics, metabolites, cerebroprotectors, antidepressants and drugs with hypocholesterolemic action, in certain doses and administration regimen. The method provides effective treatment due to the complex effect on various pathogenetic links of the disease, taking into account the specific age and neuropsychic characteristics of this group of patients.

However, the authors do not indicate which immunomodulators were used and what is the scheme of their use. In addition, from the description of the effectiveness of the method, it is not clear whether the clinical effect will be reproducible in a contingent of patients who do not have the age and neuropsychic characteristics given by the authors.

The technical result of the proposed method: the elimination of postherpetic neuralgia and the lengthening of the interrecurrent period after suffering herpes zoster, the relief of clinical manifestations of herpes zoster for up to 10 days, including pain, allodynia, insomnia.

To achieve this goal, we examined 40 patients who are hospitalized at the clinical base of the VSMU. N.N. Burdenko at the Voronezh Regional Clinical Infectious Diseases Hospital in 2021 and 2022 with a diagnosis of herpes zoster, gangliocutaneous form. The diagnosis was made in accordance with current national clinical guidelines for infectious diseases.

Among the clinical manifestations of herpes zoster in all patients upon admission, the following were observed: asthenovegetative syndrome, vesicular rash in the form of groups of vesicles on a hyperemic background of the skin, with unilateral localization and characteristic distribution over the skin within one dermatomazone of the skin, innervated by the nerve fibers of one dorsal nerve root, soreness along the rash, insomnia due to severe pain syndrome, allodynia. Patients were admitted on the 2-3rd day of the disease at the stage of rashes.

The inclusion criteria for patients were: age over 18 years, verified diagnosis of herpes zoster, gangliocutaneous form, with lesions of the dermatome innervated by the spinal ganglia, informed consent to participate in the study, recurrence of herpes zoster within a calendar year. The exclusion criteria for patients were as follows: the presence of HIV infection, indications of intolerance to any of the Superlymph components, a history of autoimmune and oncological diseases.

Patients received basic therapy, etiotropic and pathogenetic, in accordance with the available clinical guidelines for the treatment of herpes zoster. As an etiotropic therapy, acyclovir was used orally at a dosage of 800 mg 5 times a day for 10 days, prescribed from the first day of admission to the hospital. Pathogenetic therapy consisted in the local treatment of the skin lesions with a solution of aniline dye (brilliant green) once a day from the first day of admission to the hospital until the end of the eruptive period. To relieve pain, amitriptyline and gabapentin were prescribed as needed on days 3-4 of hospitalization.

Patients were divided into 2 groups depending on the treatment regimen used by simple randomization.

The main group, consisting of 20 patients, from the first day of admission to the hospital was prescribed basic therapy in combination with Superlymph 25 IU in the form of suppositories rectally 2 times a day for 10 days.

The control group, consisting of 20 patients, received only basic therapy. The results of treatment are presented in the table.

When studying the clinical efficacy of different methods of treatment, it was found that in the main group of patients the eruptive period was 3.3±0.21 days, in the control group - 5.5±0.4 days, respectively (P<0.05).

Subjectively, patients noted the disappearance of pruritus and burning sensation along the course of the rashes according to the questionnaire data at 4±0.12 days of treatment in the main group, and by 6±0.24 days of therapy in the control group (p<0.05).

In patients of the main group, there was a tendency to rapid relief of pain syndrome, in comparison with the control group, based on the CRS pain assessment scale. This was manifested by an improvement in well-being, appetite, the disappearance of insomnia, a decrease in the intensity of pain along the affected dermat.

In the control group, 90% of patients rated the severity of the pain syndrome at 7 or more points - a strong pain syndrome, and only 10% rated it from 4 to 6 points, which corresponds to a moderate pain syndrome. In the main group, the majority - 85% rated pain from 1 to 3, which is regarded as a weak pain syndrome, 15% put 3-5 points - moderate pain in the acute period of the disease.

To stop the pain syndrome, all patients from the control group required the appointment of pathogenetic pain therapy: antidepressants (amitriptyline) and gabapentin by the 3rd-4th day of hospitalization, and in the main group, only one patient was prescribed such therapy on the 4th day of hospitalization.

A significant reduction in the frequency of bacterial skin infection was revealed, namely the appearance of pustular elements in the area of the affected dermatome: in the control group, bacterial superinfection was noted in 35% of patients, while only one patient - 5% of the main group developed this complication.

A decrease in the duration of allodynia was noted statistically significant in the main group: 6.2±0.32, while in the control group this period was 8.5±0.25 days (p<0.05).

Normalization of sleep in patients in the main group occurred by 5±0.11 days of treatment, and patients from the control group noted the cessation of insomnia only by 7±0.18 days of hospitalization (p<0.05).

During the treatment, a decrease in the area of skin lesions in the area of innervation of the affected dermatome was noted: before treatment in the main group, the area of skin lesions was 179±0.72 cm ² , in the control group 164±0.72 cm ² . Against the background of the prescribed treatment, the area of skin lesions by day 5 decreased to 63±0.54 cm ² , in the control group to 88±0.32 cm ² .

In the long-term period, the frequency of postherpetic neuralgia in the compared groups attracts attention: none of the patients of the main group noted the persistence of pain after discharge from the hospital, while in the control group more than half of the patients - 60% turned after discharge from the hospital for a consultation with a neurologist and they were diagnosed with postherpetic neuralgia, which required medical correction: the appointment of gabapentin and B vitamins and follow-up.

Another important result was the lengthening of the interrecurrent period: none of the patients from the main group had a recurrence of herpes zoster within six months after therapy, and in the control group, 8 patients (40%) sought medical help during this time period with a relapse of herpes zoster. herpes.

The inclusion of a drug containing cytokines and antimicrobial peptides in the complex treatment of herpes zoster leads to a prolongation of the interrecurrent period and the elimination of cases of postherpetic neuralgia, improves the effectiveness of therapy, reduces the time of regression of clinical manifestations, such as the duration of the period of rashes, allodynia, insomnia, and the severity of pain syndrome , reduces the area of skin lesions, the incidence of bacterial superinfection.

Clinical examples

Example 1. Patient K., aged 63, was admitted to VOKIB with complaints of a rash on the right side, itching, burning along the rash, pain in the chest on the right, insomnia, poor appetite. 3 days ago, shooting pains appeared in the right side, Diclofenac gel applied topically on its own, without effect. On the eve of the day of hospitalization, "vesicles" appeared on the right in the abdomen, the number of which increased. He turned to a dermatologist and was referred for a consultation with an infectious disease specialist (Fig. 1).

In the anamnesis, a similar episode occurs repeatedly over the past year. Chronic diseases: hypertension, coronary artery disease, obesity.

Objectively: General condition of moderate severity. Consciousness is clear. The skin is of normal color, dry, warm. On the skin of the abdomen on the edematous and hyperemic area of the skin - groups of vesicles filled with serous contents, spreading along the dermatome. Visible mucous membranes are pink, moist. Tongue moist, slightly coated with white coating.

The pharynx is not hyperemic, the tonsils are not hypertrophied, there are no raids. Peripheral lymph nodes are not palpable. Vesicular breathing in the lungs. There are no rales on auscultation. Heart sounds are rhythmic, muffled. Pulse - 90 beats / min., rhythmic. AD-130/80 mm Hg The abdomen is soft, painless on palpation, enlarged due to subcutaneous fat. The liver and spleen are not palpable. Pasternatsky's symptom is negative. Urination free, painless. The chair is regular, decorated. There are no meningeal symptoms.

The patient was prescribed the following drugs: acyclovir 800 mg 5 times a day orally in combination with Superlymph 25 IU, rectal suppositories 2 times a day.

By the 4th day of treatment, the appearance of new elements was no more, at the same time the patient noted the disappearance of skin itching and burning in the affected areas. Sleep returned on day 5. The severity of the pain syndrome according to the CRS scale was 2 points, which corresponds to a mild pain syndrome, and, accordingly, the appointment of pain therapy was not required. Allodynia disappeared on the 7th day of treatment. There was no bacterial infection during hospitalization. The patient was discharged on day 11 with recovery. When questioned by phone after 6 months, this patient found that there were no recurrences of herpes zoster during this period.

Example 2. Patient M., 78 years old, was admitted to VOKIB with complaints of burning pain in the right shoulder, a rash on the skin on the right, itching, burning along the rash, poor sleep, weakness. Diseases are associated with hypothermia. Yesterday, intense pain appeared, she took NSAIDs (nimesil), without effect. Today, a rash appeared on the surface of the skin in the region of the collarbone and shoulder on the right, and she independently applied for a consultation with an infectious disease specialist (Fig. 2).

According to the anamnesis, she had herpes zoster 9 months ago. Chronic diseases: hypertension, hypothyroidism.

Objectively: General condition of moderate severity. Consciousness is clear. The skin is of normal color, dry, warm. On the skin of the right shoulder, on an edematous and hyperemic area of the skin, there are groups of vesicles filled with serous contents, spreading along the course of the dermatome. Visible mucous membranes are pink, moist. Tongue moist, slightly coated with white coating. The pharynx is not hyperemic, the tonsils are not hypertrophied, there are no raids. Peripheral lymph nodes are not palpable. Vesicular breathing in the lungs. There are no rales on auscultation. Heart sounds are rhythmic, muffled. Pulse - 80 beats / min., rhythmic. AD-125/80 mm Hg The abdomen is soft, painless on palpation. The liver and spleen are not enlarged. Pasternatsky's symptom is negative. Urination free, painless. The chair is regular, decorated. There are no meningeal symptoms.

The patient was prescribed the following drugs: acyclovir 800 mg 5 times a day orally.

Against the background of therapy, only on the 6th day of treatment did the appearance of new elements stop, at the same time the patient noted the disappearance of skin itching and burning in the lesions (Fig. 3). The severe pain syndrome on the CRS scale was 6 points, which corresponds to a severe pain syndrome and required the appointment of pain therapy on the 4th day of hospitalization (amitriptyline and gabapentin). On the 7th day, sleep was restored, at the same time allodynia disappeared. At the 8th hospitalization, a bacterial infection was noted: pustules with purulent contents formed in place of the vesicles. The patient was discharged on day 15 with recovery. When questioning over the phone after 6 months of this patient, it was found that the patient was observed by a neurologist on an outpatient basis for postherpetic neuralgia, received a course of amitriptyline, gabapentin and B vitamins. Herpes zoster recurrence was noted 4 months after discharge from the hospital, she was treated on an outpatient basis.

Description for the figures.

Figure 1. Photo of the area of skin lesion patient K., 63 years old, gangliocutaneous form, on the 5th day of hospitalization with a diagnosis of herpes zoster, gangliocutaneous form.

1 - measuring palette in increments of 1 cm

2 - drying vesicle with scale formation

Figure 2. Photo of the area of skin lesions of the patient M., 78 years old, diagnosed with herpes zoster, gangliocutaneous form, on the day of hospitalization.

2 - drying vesicle with scale formation

3 - grouped vesicles, the skin is hyperemic.

Figure 3. Photo of the area of the skin lesions of the patient M., 78 years old, diagnosed with herpes zoster, ganglionic form, on the 5th day of treatment in the hospital.

2 - drying vesicle with scale formation

4 - granulation.

Claims (1)

A method for the treatment of herpes zoster, including the appointment of acyclovir orally, from the first day of admission to the hospital, at a dosage of 800 mg 5 times a day for 10 days and local treatment of the skin lesion with a solution of aniline dye once a day from the first day of admission to the hospital until the end of the eruptive period, characterized in that the drug Superlymph 25 IU is additionally prescribed in the form of suppositories rectally 2 times a day for 10 days.

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