Federal guidelines for the management of patients with vitiligo

RUSSIAN SOCIETY DERMATOVENEREOLOGY and cosmetology

FEDERAL clinical guidelines
The behavior of patients with vitiligo

Moscow 2013

Personal composition of the working group on preparation of the federal guideline for profile "Dermatology", "Vitiligo" section:

Volnukhin Vladimir Anatolievich - a leading researcher at the Department of development of physiotherapy treatments FGBU "State Scientific Center of dermatology and cosmetology» Russian Ministry of Health, MD, Professor

METHODOLOGY

The methods used for the collection / selection of evidence:

search in electronic databases.

Description of the methods used for the collection / selection of evidence:

evidence base for recommendations are publications included in the Cochrane Library, EMBASE and MEDLINE databases.

The methods used to assess the quality of evidence and strength:

• The consensus of experts;
• Assessment of significance according to the rating scheme (scheme attached).

The rating scheme force estimating recommendations (Table 1):

levels of evidence	Description
1++	Meta-analyzes of high-quality systematic reviews of randomized controlled trials (RCTs), or RCTs with a very low risk of bias
1+	Well-conducted meta-analyzes, systematic, or RCTs with a low risk of bias
1-	Meta-analyzes, systematic, or RCTs with a high risk of bias
2++	High-quality systematic reviews of case-control or cohort studies. High-quality reviews case-control or cohort studies with a very low risk of mixing effects or systematic errors and the average probability of a causal relationship
2+	Well-conducted case-control or cohort studies with an average risk of mixing effects or systematic errors and the average probability of a causal relationship
2-	Case-control or cohort studies with a high risk of mixing effects or systematic errors and the average probability of a causal relationship
3	Non-analytic studies (for example case reports, case series)
4	expert opinion

The methods used for the analysis of the evidence:

• A review of published meta-analyzes;
• Systematic reviews of the evidence from the tables.

The methods used for formulating the recommendations:

The consensus of experts.

The rating scheme force estimating recommendations (Table 2):

Force	Description
BUT	At least one meta-analysis, systematic review or RCT evaluated as ++ 1 is directly applicable to the target population and demonstrate the robustness of the results or group of evidence, including the results of studies evaluated as 1+, directly applicable to the target population and the results demonstrate the overall stability
AT	Evidence Unit, which includes the results of studies rated as 2 ++, directly applicable to the target population and demonstrating overall stability results or Extrapolated evidence from studies rated as 1 ++ or 1+
FROM	Group of evidence, including the results of studies rated as 2+, directly applicable to the target population and demonstrating overall sustainability of results; or Extrapolated evidence from studies rated as 2 ++
D	Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+

Indicators benign practices (GoodPracticePoints – GPPs):

Recommended benign practice is based on the clinical experience of the working group to develop recommendations.

Economic analysis:

value not analyzed and publications pharmacoeconomics not analyzed.

Method validation guidelines:

• External peer review;
• Internal expert judgment.

Description of the method validation guidelines:

These recommendations are in the preliminary version reviewed by independent experts.

Comments received from experts, systematized and discussed by the working group. Introduced as a result of this change in the recommendation were recorded. If changes were not made, the reasons for refusal registered by the change.

Consultation and expert assessment:

A preliminary version was put up for discussion at the site FGBU "State Scientific Center of dermatology and cosmetology" the Ministry of Health Russia to persons who are not involved in the development of recommendations, were able to participate in the discussion and improvement recommendations.

Working group:

For the final version of the recommendations and quality control re-analyzed by the working group.

Key recommendations:

The strength of the recommendation (A-D) is in presenting text recommendations.

VITILIGO

Cipher on the International Classification of Diseases ICD-10

L80

DETERMINATION

Vitiligo - a chronic disease of unknown etiology, characterized by the appearance in different areas body depigmented spots and bleached hair due to the destruction and reduce the number of melanocytes in skin.

Etiology and epidemiology

The etiology of vitiligo is not yet clear. There are several hypotheses of the pathogenesis of the disease - a genetic, autoimmune, neurohumoral, oxidative stress, melanotsitorragii, autotsitotoksicheskaya, converged.

According to most experts, the leading role in the damage of melanocytes and violation of melanogenesis in the skin of patients with vitiligo is an autoimmune mechanism is attached.

Vitiligo prevalence in the general population is between 0.5 and 2%; the prevalence of the disease among children and adolescents is not different from the prevalence among the adult population (B) (1).

CLASSIFICATION (2):

unsegmented bar vitiligo

• generalized vitiligo
• akrofatsialnoe vitiligo
• universal vitiligo
• mixed vitiligo (combination unsegmented bar and segmental vitiligo)
• vitiligo mucous membranes (the presence of more than one lesion)
• rare variants

segmental vitiligo

• uni-, bi- or plyurisegmentarnoe vitiligo

Non-deterministic / unclassified vitiligo

• focal vitiligo
• Vitiligo of the mucous membranes (the presence of the lesion)

CLINICAL PICTURE

In typical cases, the skin, mucous membranes rarely appear single or multiple depigmented patches of milky-white color, various shapes and sizes, with clear boundaries. The spots often occur at the site of skin trauma (Koebner phenomenon), are prone to peripheral growth and mergers. The foci of depigmentation can be observed areas of residual pigmentation, rarely - skin hyperpigmentation, especially pronounced on the periphery of the lesions.

hearths vitiligo usually occur on the skin of the eyelids, periorbital area, neck, armpits, trunk, elbows, forearms, dorsum of the hands, genitals, perineum, knee and ankle joints, the knees, the back surface Stop. Sometimes they are combined with one or more halo nevi (pigmented nevi depigmented with halo).

Some patients in the centers of depigmentation observed bleached hair (in the growth of eyelashes and eyebrows, at least - on the head, armpits, pubic and other body parts).

In some cases, the appearance of white spots can be accompanied by itching, erythema and skin desquamation.

DIAGNOSTICS

The diagnosis of vitiligo is based on the history and clinical picture of the disease - the presence of spots on the skin milky white with clear contours and the typical localization. At the initial examination it is advisable to record the type and location of white spots by photographing. For a more clear visualization of lesions vitiligo and differential diagnosis is recommended viewing them using a Wood's lamp.

Laboratory research

• clinical blood test;
• urinalysis;
• blood chemistry (glucose levels, hepatic and renal function);
• serum study level of antibodies to thyroglobulin and thyroid peroxidase (to detect concomitant autoimmune disease it is advisable, if possible, the study of blood other antibody: antinuclear antibodies, antibodies to parietal cells of the stomach, etc.).

microscopic examination Skin biopsies shown in cases where the diagnosis is not clear and is clinically impossible to determine the version of chromatopathy.

To exclude associated diseases, including other autoimmune disorders, recommended medical consultation (pediatrician), endocrinologist, otolaryngologist, gynecologist, ophthalmologist. According to the testimony appointed consultation with other professionals.

differential diagnosis

Differential diagnosis of vitiligo is most often carried out with the multicolored ringworm, depigmented nevi, anemic nevus, lichen sclerosus, lichen simplex, zoster white, teardrop gipomelanozom idiopathic, secondary leucoderma, growing at atopic dermatitis, syphilis, Lupus erythematosus, leprosy, pint.

Less commonly differentiated from vitiligo pebaldizma, albinism syndrome Vogt-Koyanagi-Harada syndrome Bloch-Sulzberger syndrome Klein-Waardenburg syndrome Wolfe gipomelanoza Ito, tuberous sclerosis, depigmentation induced trauma or chemical substances.

TREATMENT

The goals of treatment:

• stop the progression of the disease;
• reduce the activity of the pathological process;
• restore pigmentation in vitiligo outbreaks and reduce the incidence of skin lesions;
• improve the quality of life of patients.

General comments on the therapy.

With limited forms of vitiligo unsegmented bar with lesion area of ​​not more than 10-20% of the body surface, and when egmentarnom vitiligo treatment method of choice is the topical medication means. In cases where no effect on their prescribed use medium-wave ultraviolet irradiation treatment or ultraviolet excimer light with a wavelength of 308 nm.

In patients with common forms of vitiligo affected area more than 10-20% of the body surface by the methods of choice are phototherapy with narrowband wavelength of 311 nm or broadband UV treatment medium wave with wavelength 280-320 nm.

Patients aged 18 years and older in the case of absence of the effect of treatment with other therapeutic agents shown holding PUVA therapy with oral administration of a photosensitizer.

The maximum allowable number of photographic processes and PUVA therapy in the treatment of vitiligo patients is not established. Taking into account data on the increase in the incidence of skin cancer during mnogokursovoy PUVA therapy to patients with psoriasis, as well as in theory possible risk of carcinogenic activity large cumulative doses of medium wave ultraviolet radiation, vitiligo patients with I-III skin phototype recommended lifetime of not more than 150 PUVA therapy procedures 200 and narrowband phototherapy with long procedures wavelength 311 nm (3).

Treatment of patients with vitiligo universal form of topical corticosteroid agents, topical calcineurin inhibitors and methods of phototherapy in most cases is not efficient.

The patient should be apprised of the long duration of treatment of the disease ranging from 6 months to 1 year or more.

regimens

drug therapy

1. Topical glucocorticosteroid agent (A) (4, 5)

The use of topical glucocorticoid drugs is by first-line treatment of patients with disabilities forms unsegmented bar with vitiligo affected area not more than 10-20% of the body surface and patients segmental vitiligo. Literature data indicate that moderate effectiveness of treatment of vitiligo with topical glucocorticosteroids (A) (4-6).

• methylprednisolone aceponate, cream, ointment topically 1 time per day in the form of applications

or

• alklometezona dipropionate cream, ointment, 1 time a day topically in the form of applications

or

• betamethasone dipropionate cream, ointment topically 1 time per day in the form of applications

or

• clobetasol propionate cream, ointment topically 1 time per day in the form of applications.

Treatment with topical glucocorticosteroids carried out on a continuous or intermittent pattern.

In the treatment of children prescribed continuous scheme glucocorticosteroid drugs of moderate or high activity 1 time per day for 3 months. Adults are recommended prescribe high or very high degree of activity 1 times a day for 4-6 months.

By intermittent scheme commonly prescribed drugs high or very high degree of activity: application is performed 1 time per day for 2-3 weeks, followed by a one- or two-week break. In the absence of side effects of repeated courses 4-6 is performed.

In cases of prolonged use of topical glucocorticosteroids should consider the possibility development of local side effects (steroid acne, skin atrophy, striae, hirsutism, infectious complications). When applied to a large surface of the body there is the risk of systemic effects glucocorticosteroid drugs as a result of skin absorption.

2. Topical calcineurin inhibitors (A).

When treating patients with limited forms of vitiligo in cases where no effect on the application glucocorticoid topical formulations are an alternative means of topical inhibitors calcineurin.

Several randomized, including placebo-controlled, studies have established the effectiveness of treatment of vitiligo, in both adults and children, 0.1% tacrolimus ointment (A) (6-9). When comparing the results of therapy vitiligo children 0.1% tacrolimus ointment preparations and the clobetasol propionate statistically significant differences were not detected (A) (6, 9).

Prepared positive effect in the treatment of children tacrolimus ointment 0.03% (C) (10-12).

The efficiency of the treatment of vitiligo pimecrolimus cream 1% (A) (13, 14). A satisfactory effect is observed mainly in the lesions localized on the face.

• tacrolimus 0.1% ointment topically two times daily as applications

or

• tacrolimus ointment 0.03% outwardly 2 times per day in the form of applications

or

• Pimecrolimus 1% Cream outwardly 2 times per day in the form of applications.

The course of treatment with topical calcineurin inhibitors of 3 months or more.

Application of topical calcineurin inhibitors safer compared with treatment with topical glucocorticosteroids, since it does not cause skin atrophy.

Treatment with topical calcineurin inhibitors is not recommended to be combined with phototherapy or sun exposure of the skin. It is believed that with such a combination may increase the risk of skin tumors.

Note. The instructions for medical use of the ointment of tacrolimus and pimecrolimus cream vitiligo not included in the indications for use.

Drug-free treatment

1. Narrowband medium wave ultraviolet therapy with a wavelength of 311 nm (A).

Narrowband phototherapy with a wavelength of 311 nm is one of the most effective methods for the treatment of vitiligo.

In a randomized study demonstrated the efficacy of monotherapy vitiligo patients narrowband ultraviolet radiation having a wavelength 311 nm: during a 6-month course of treatment the percentage of repigmentation of vitiligo in foci was 42.9% in the control sections - 3.3% (A) (15). Patients unsegmented bar Vitiligo has a higher efficiency of narrowband phototherapy in comparison with the therapy PUVA (A) (16).

• Exposure begin with a dose of 0.1-0.25 J / cm², The procedure is carried out with the regime of 2-3 times a week (but not 2 days in a row). Each subsequent procedure a single dose increased by 5-20% before the advent of mild to moderate erythema, are not itchy or painful sensations. Later in the presence of a single dose of erythema left constant in the absence of erythema dose increased by 5-20%. On the course administered from 20 to 100 procedures, and more.

2. Broadband medium-wave ultraviolet therapy (syn. selective phototherapy, wavelength 280-320 nm) (C).

Carrying a 12-month course of therapy broadband medium-wave ultraviolet radiation patients widespread vitiligo possible to achieve good results (repigmentation of more than 75% area affected) in 57.1% cases (C) (17). It is shown that the broadband medium wave ultraviolet therapy reduces disease activity flow (C) (18).

• Irradiation begin with a dose equal 0,01-0,025 J / cm² or component of 25-30% of the minimum erythemal dose. Subsequent increase unit doses every 2-4 procedure - before the weak or moderately severe erythema, are not itchy or painful sensations, after which the dose is left constant. The maximum single dose ranges from 0.1 to 0.59 J / cm². Procedures are carried out with the regime of 2-3 times a week. On Course 20-100 is prescribed procedures and more.

3. ultraviolet excimer laser radiation, treatment with a wavelength of 308 nm (A).

In monotherapy vitiligo patients ultraviolet excimer laser light having a wavelength of 308 nm repigmentation of the skin of varying severity was observed in 85% of lesions (A) (19).

The greatest effect is achieved in the foci vitiligo disposed in ultraviolet light sensitive areas (20).

• It is believed that the minimum erythemal dose foci vitiligo equivalent to the minimal erythemal dose (100 mJ / cm²) Recorded in patients with skin phototype I, in connection with which the irradiation starts with a dose equal to 50-100 mJ / cm². When the localization of foci vitiligo on the face, neck and underarm initial dose of 50 mJ / cm² (0.5 minimal erythema dose). When the location of the lesions on the trunk or limbs, treatment is initiated with a single dose of 100 mJ / cm² (1 minimal erythemal dose). The procedures carried out with the mode 2 times per week. the irradiation dose is increased each procedure or every 2nd procedure at 25-100 mJ / cm² (0.25-1 Minimal erythemal dose) until a weak or moderate erythema, not accompanied by itching or painful sensations. In subsequent procedures, the dose is left constant or increase by 25-50 mJ / cm² (0.25-0.5 minimal erythema dose) depending on the presence and intensity of erythema, as well as the individual patient acceptance of treatment. On the course administered from 20 to 60 procedures and more.

4. Treatment excimer ultraviolet monochromatic light with a wavelength of 308 nm (A).

In a randomized, controlled trials has a higher efficiency of treatment of vitiligo excimer monochromatic UV light with a wavelength of 308 nm compared with narrowband phototherapy with wavelength 311 nm: repigmentation over 75% of the lesions was achieved in 37.5%, respectively, and 6% of vitiligo foci (A) (21).

In comparing the effectiveness of treatment with UV excimer limited vitiligo monochromatic light and UV excimer laser statistically significant differences found (A) (22).

• Depending on the localization of foci depigmentation starting dose of 0.05-0.2 J / cm² (50-70% of the minimum erythemal dose). The procedures carried out with the mode 2 times per week. A single dose of radiation increases each procedure or procedures in 1-2 0.05-0.1 J / cm² (10-40% of the minimal erythema dose) before the appearance of mild to moderate erythema, is not accompanied by itching or pain, then left constant. On the course administered from 20 to 60 procedures and more.

5. PUVA therapy with oral administration of a photosensitizer (A).

Randomized controlled studies show the effectiveness of PUVA therapy in patients with vitiligo (A) (16, 23). However, treatment by this method is accompanied by a higher number of side effects.

• Ammi majus fruit furokumariny, tablets, 0.8 mg / kg body weight of a single oral dose of 2 hours before the irradiation with long-wave ultraviolet light (wavelength 320-400 nm)

or

• methoxsalen, capsules, 20 mg (2 capsules) inside once per 2-4 hours prior to irradiation with long-wave ultraviolet light (wavelength 320-400 nm)

Irradiation begin with a dose of UVA constituting 25-50% of the minimum phototoxic dose, or c 0,1-0,5 J / cm². Procedures are carried out 2-3 times a week (but not 2 days in a row). In the absence of erythema single dose is increased every second or third procedure on 10-20% or 0.2-0.5 J / cm². When the mild erythema dose is left constant. The maximum value of a single dose of irradiation - 5 J / cm².

PUVA treatment is administered as repeated courses consisting of 15-25 treatments at intervals of 1-3 months or one year long, including 100 and more procedures.

Note that this method of treatment has several side effects that limit its use: photosensitivity eyes and skin, the risk of cataracts and skin cancer. PUVA therapy often leads to severe hyperpigmentation and formation of a sharp contrast between the affected, repigmentirovannoy and apparently healthy skin.

special situations

treatment of children

In children suffering from vitiligo, the first line of therapy is topical glucocorticosteroids.

In the absence of data on the safety and long-term effects of UV therapy children crednevolnovuyu ultraviolet therapy and treatment by an excimer light with a wavelength of 308 nm to children under 12 years are only recommended for severely valid indications in view of the ratio of expected benefits and potential risk.

The use of PUVA therapy in children is contraindicated.

treatment of pregnant women

vitiligo treatment in pregnant women is not recommended.

the results of the treatment requirements

• termination of new and increase existing lesions;
• the absence of inflammation on the skin;
• restoring pigmentation in vitiligo foci;
• improving the quality of life of patients.

Tactics in the absence of the effect of treatment

If there is no effect of the use of topical glucocorticoid is recommended assignment means of topical calcineurin inhibitors.

In the absence of effect of drug treatment is recommended to assign one of the methods phototherapy or PUVA therapy.

PREVENTION

Patients are advised to avoid stressful situations, intense sun exposure, skin trauma. In sunny weather it is necessary to protect the affected skin from sun damage sunscreen agents.

Bibliography

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