What are the FDA-approved indications for acitretin. How does acitretin work in treating psoriasis. What are the off-label uses of acitretin in dermatology. What precautions should be taken when using acitretin.

Understanding Acitretin: A Powerful Retinoid for Psoriasis Treatment

Acitretin is a second-generation retinoid that plays a crucial role in the treatment of various dermatological conditions, particularly psoriasis. As a synthetic compound with similar activity to vitamin A, acitretin offers a range of therapeutic benefits for patients struggling with severe skin disorders. This article delves into the intricacies of acitretin, exploring its uses, mechanism of action, and important precautions for healthcare providers and patients alike.

FDA-Approved Indications for Acitretin

The U.S. Food and Drug Administration (FDA) has approved acitretin for several specific uses in the treatment of psoriasis. These include:

• Severe plaque-type psoriasis
• Generalized pustular psoriasis
• Localized pustular psoriasis
• Combination therapy with ultraviolet B (UVB) or psoralen ultraviolet A (PUVA)
• Combination therapy with cyclosporine
• Combination therapy with biologic therapies

Is acitretin effective as a monotherapy for psoriasis? Yes, acitretin is the only systemic retinoid that is FDA-approved for psoriasis and has shown efficacy when used alone.

Off-Label Uses of Acitretin in Dermatology

While acitretin’s primary indication is for psoriasis, dermatologists have found it beneficial in treating various other skin conditions. Some off-label uses include:

• Chemoprevention of nonmelanoma skin cancers in solid organ transplant recipients
• Darier disease
• Pityriasis rubra pilaris (PRP)
• Ichthyoses, such as lamellar ichthyosis
• Grover disease (transient acantholytic dermatosis)
• Lichen planus
• Lupus erythematosus

Can acitretin be used to prevent skin cancers in transplant patients? Yes, it has been used as a chemoprevention measure for nonmelanoma skin cancers in solid organ transplant recipients.

The Mechanism of Action: How Acitretin Works

Understanding how acitretin functions at the cellular level is crucial for appreciating its therapeutic effects. The mechanism of action involves several key steps:

1. Binding to cytosolic retinoic acid-binding protein (CRABP)
2. Transport to the nucleus
3. Interaction with nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs)
4. Formation of heterodimers or homodimers
5. Binding to DNA regulatory sequences (retinoid acid response elements or RAREs)
6. Activation of gene transcription

How does acitretin differ from other retinoids in its receptor binding? Acitretin competes with retinoic acid for CRABP and can activate multiple RARs, but it does not directly bind to them.

Anti-inflammatory and Anti-proliferative Effects

Acitretin exhibits both anti-inflammatory and anti-proliferative properties, which contribute to its efficacy in treating psoriasis and other skin conditions. It acts by:

• Normalizing keratinocyte differentiation in the epithelium
• Inhibiting the expression of proinflammatory mediators
• Modulating immune system function
• Inducing apoptosis in certain cell types
• Inhibiting tumor promotion

Acitretin vs. Other Retinoids: A Comparative Analysis

To better understand acitretin’s place in dermatological treatment, it’s helpful to compare it with other retinoids:

What makes acitretin unique among retinoids? Acitretin is relatively water-soluble compared to its predecessor, etretinate, and has less deposition in adipose tissue.

Precautions and Contraindications for Acitretin Use

While acitretin can be highly effective, it’s essential to be aware of its potential risks and contraindications:

Pregnancy and Teratogenicity

Acitretin is highly teratogenic and absolutely contraindicated in pregnant women or those who may become pregnant during treatment or within 3 years after discontinuation. Strict contraceptive measures are mandatory.

Liver Function

Regular monitoring of liver function is necessary, as acitretin can cause hepatotoxicity. Patients with pre-existing liver disease should be closely monitored or may not be suitable candidates for treatment.

Lipid Profile

Acitretin can elevate triglycerides and cholesterol levels. Regular lipid profile checks are recommended, especially in patients with a history of hyperlipidemia.

Skeletal Effects

Long-term use of acitretin may lead to hyperostosis and premature epiphyseal closure. Caution is advised in patients with a history of bone disorders.

Photosensitivity

Patients should be advised to avoid excessive sun exposure and use sun protection, as acitretin can increase photosensitivity.

How long should contraception be continued after stopping acitretin? Women of childbearing potential should use effective contraception for at least 3 years after discontinuing acitretin due to its long half-life and potential to be converted back to etretinate in the body.

Monitoring and Patient Management During Acitretin Therapy

Proper monitoring is crucial for the safe and effective use of acitretin. Healthcare providers should implement the following monitoring strategies:

• Baseline liver function tests, lipid profile, and pregnancy test (for women of childbearing potential)
• Regular follow-up liver function tests and lipid profiles (initially monthly, then quarterly)
• Periodic pregnancy tests for women of childbearing potential
• Monitoring for signs of depression or mood changes
• Regular skin examinations to assess treatment efficacy and potential side effects
• Bone density scans for patients on long-term therapy

How often should liver function tests be performed during acitretin therapy? Initially, liver function tests should be performed monthly. After the first few months, if results remain stable, the frequency can be reduced to quarterly.

Interprofessional Team Strategies for Optimal Acitretin Use

Effective management of patients on acitretin therapy requires a collaborative approach involving multiple healthcare professionals:

Dermatologist’s Role

The dermatologist is typically the primary prescriber and oversees the overall treatment plan. They are responsible for:

• Initial patient assessment and acitretin prescription
• Monitoring treatment efficacy and adjusting dosage as needed
• Conducting regular skin examinations
• Coordinating with other healthcare providers

Primary Care Physician’s Involvement

The primary care physician plays a crucial role in:

• Monitoring overall patient health
• Conducting regular health check-ups
• Managing comorbidities that may affect acitretin therapy

Pharmacist’s Contribution

Pharmacists are essential for:

• Educating patients on proper medication use and potential side effects
• Monitoring for drug interactions
• Ensuring appropriate contraception counseling

Laboratory Technician’s Role

Laboratory technicians are responsible for:

• Conducting regular blood tests for liver function and lipid profiles
• Performing pregnancy tests as required
• Promptly reporting abnormal results to the healthcare team

How can interprofessional collaboration improve patient outcomes in acitretin therapy? By fostering open communication and coordinated care among healthcare providers, patients can receive more comprehensive monitoring, timely interventions, and better management of potential side effects, ultimately leading to improved treatment outcomes and patient safety.

Future Directions and Research in Acitretin Therapy

As our understanding of retinoids and their effects on various skin conditions continues to evolve, several areas of research are being explored to enhance the use of acitretin:

Combination Therapies

Researchers are investigating novel combination therapies to potentially enhance the efficacy of acitretin while minimizing side effects. Some promising areas include:

• Combination with newer biologic agents for psoriasis
• Synergistic effects with other anti-inflammatory medications
• Exploration of topical-systemic combination regimens

Targeted Drug Delivery

Advancements in drug delivery systems may lead to more targeted applications of acitretin, potentially reducing systemic side effects. Areas of investigation include:

• Nanoparticle-based delivery systems
• Transdermal delivery methods
• Tissue-specific targeting techniques

Genetic Markers for Treatment Response

Identifying genetic markers that predict treatment response to acitretin could help personalize therapy and improve outcomes. Research is focusing on:

• Pharmacogenomic studies to identify responder and non-responder profiles
• Genetic risk factors for adverse events
• Biomarkers for monitoring treatment efficacy

Long-term Safety Studies

Continued research into the long-term safety profile of acitretin is crucial, particularly for patients requiring extended treatment. Areas of interest include:

• Effects on bone health over extended periods
• Cardiovascular risk assessment in long-term users
• Potential protective effects against certain cancers

What potential benefits could targeted drug delivery systems offer for acitretin therapy? Targeted delivery systems could potentially allow for higher local concentrations of acitretin in affected skin areas while minimizing systemic exposure, potentially reducing side effects and improving the overall safety profile of the medication.

Patient Education and Support for Acitretin Users

Effective patient education is crucial for the success of acitretin therapy. Healthcare providers should focus on the following aspects when counseling patients:

Understanding the Medication

Patients should be thoroughly informed about:

• The purpose of acitretin and its expected benefits
• Proper dosing and administration
• The importance of adherence to the treatment regimen
• Potential side effects and when to seek medical attention

Contraception and Pregnancy Prevention

For women of childbearing potential, emphasis should be placed on:

• The critical importance of effective contraception
• The need for contraception during treatment and for 3 years after discontinuation
• Regular pregnancy testing requirements
• The severe risks of pregnancy while on acitretin

Lifestyle Modifications

Patients should be advised on necessary lifestyle changes, including:

• Avoiding excessive sun exposure and using appropriate sun protection
• Limiting alcohol consumption due to potential liver effects
• Maintaining a healthy diet to manage lipid levels
• Regular exercise, as appropriate for their condition

Follow-up and Monitoring

Educate patients on the importance of:

• Regular follow-up appointments
• Compliance with blood tests and other monitoring procedures
• Promptly reporting any new symptoms or side effects

How can healthcare providers ensure patients fully understand the risks and responsibilities associated with acitretin therapy? Providers can use a combination of verbal counseling, written materials, and possibly video resources to educate patients. Additionally, having patients sign informed consent forms and contraception agreements can reinforce the importance of adhering to safety guidelines.

In conclusion, acitretin represents a powerful tool in the dermatologist’s arsenal for treating severe psoriasis and other challenging skin conditions. Its unique mechanism of action, coupled with its efficacy as both a monotherapy and in combination with other treatments, makes it a valuable option for many patients. However, the potential for serious side effects and strict contraindications, particularly regarding pregnancy, necessitate careful patient selection, thorough education, and vigilant monitoring. By implementing comprehensive interprofessional team strategies and staying abreast of ongoing research, healthcare providers can optimize the use of acitretin to improve patient outcomes while minimizing risks. As our understanding of retinoids continues to evolve, acitretin is likely to remain an important component of dermatological therapy, with potential for even more refined and targeted applications in the future.

Acitretin – StatPearls – NCBI Bookshelf

Continuing Education Activity

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion. This activity reviews the indications, contraindications, and adverse events associated with acitretin so that interprofessional team members can work together to manage patients using the medication optimally.

Objectives:

• Identify the indications for acitretin.

• Describe the adverse effects/toxicity with acitretin use.

• Outline the monitoring necessary for patients on acitretin therapy.

• Review interprofessional team strategies for improving care coordination for patients undergoing acitretin therapy to improve patient outcomes.

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Indications

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion.[1][2][3]

Vitamin A exists as retinol (vitamin A alcohol), retinal (vitamin A aldehyde), and retinoic acid (RA, vitamin A acid). The body cannot synthesize vitamin A; therefore, one must acquire it in the diet through foods such as eggs and milk. Carotenoids are precursors of vitamin A that are synthesized by plants. In the intestines, beta-carotene is converted to retinal then absorbed. Each molecule of beta-carotene converts into two molecules of retinal. Researchers have observed that animals with vitamin A deficiency have epidermal hyperkeratosis, squamous metaplasia of mucous membranes, and precancerous lesions.  

Currently, three generations of synthetic retinoids exist. First-generation retinoids include tretinoin (all-trans RA), isotretinoin (13-cis-retinoic acid), and alitretinoin (9-cis RA). Second-generation retinoids include etretinate and acitretin. Third-generation retinoids include adapalene, tazarotene, and bexarotene. In 1972, Bolag developed two aromatic retinoids: etretinate and acitretin. Acitretin is the retinoic acid metabolite of etretinate. Acitretin is relatively water-soluble in comparison and has a little deposition in adipose tissue. 

FDA-approved Indication

Acitretin is FDA-approved for psoriasis (severe plaque-type psoriasis, pustular psoriasis generalized, pustular psoriasis localized), combination therapy with ultraviolet B (UVB) or psoralen ultraviolet A (PUVA), combination therapy with cyclosporine, combination therapy with biologic therapies. Acitretin is the only systemic retinoid that is FDA-approved for psoriasis and effective as monotherapy.  

Off-labeled Use

Acitretin has been used off-label in dermatology for other uses. In solid organ transplants, acitretin has served as a chemoprevention measure for nonmelanoma skin cancers. Acitretin has also been used for Darier disease, pityriasis rubra pilaris (PRP), and ichthyoses such as lamellar ichthyosis. Additionally, acitretin has been used in Grover disease (transient acantholytic dermatosis), lichen planus, and lupus erythematosus.[4]

Mechanism of Action

Retinoids bind cytosolic retinoic acid-binding protein (CRABP) that acts as the intracellular carrier transporting it to the nucleus. In the nucleus, retinoids impact transcription by binding two families of nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXR). RAR and RXR families contain three receptor subtypes: alpha, beta, and gamma that are encoded by different genes. RAR can bind with RXR forming a heterodimer. RXR can bind with itself, forming a homodimer, or bind with other nuclear receptors such as thyroid hormone receptor, vitamin D3 receptor, and peripheral peroxidase-activated receptor (PPAR). Dimers of RAR/RXR or RXR/RXR bind to DNA regulatory sequences in the promoter region, retinoid acid response elements (RAREs). Once the ligand binds, it undergoes a conformational change to release co-repressors and recruit co-activators. The retinoid-receptor complex may antagonize the action of other transcription factors, thus working indirectly. Acitretin competes with RA for CRABP. Acitretin can activate but does not bind to multiple RARs.[5][6]

Acitretin has anti-inflammatory and anti-proliferative effects. It normalizes keratinocyte differentiation in the epithelium. It also hinders the expression of proinflammatory cytokines like interleukin-6 (IL-6), migration inhibitory factor-related protein-8 (MRP-8), and interferon-gamma. The agent acts by binding and activating all nuclear subtypes of retinoid X-receptors and retinoic acid receptors.

Pharmacokinetics

Absorption: Generally administered with food and reaches peak plasma concentration in 2.7 hours (2-5 hours).

Plasma Protein Binding: 99.9%

Metabolism: The initial metabolism of acitretin involves isomerization; this differs from isotretinoin, where the initial metabolism is oxidation. Acitretin converts to isoacitretin. Acitretin is ultimately eliminated in the bile as beta-glucuronide derivatives or through the kidneys as soluble metabolites. Acitretin can undergo reverse metabolism to etretinate when acitretin is used in combination with alcohol.

Excretion:  Its metabolites, as well as conjugates of acitretin and cis-acitretin, are excreted in the feces (34% to 54%) and urine (16% to 53%).

Terminal Elimination Half-life: Following multiple-dose, acitretin has a half-life of 49 hours, and cis-acitretin has 63 hours.

Administration

Initial: Administer 25 to 50 mg orally daily as a single dose with the main meal.

Maintenance: Administer 25 to 50 mg orally daily after initial response to treatment. The maintenance dose should have its basis in clinical efficacy and tolerability.

Acitretin is available in 10 mg and 25 mg in hard gelatin capsules. In psoriasis treatment with acitretin, improvement is seen approximately at weeks 4 to 6. The maximum benefit may take between 3 to 4 months. Treatment dosing is initiated at 25 mg orally once daily. When the disease is stable, dosing is often reduced to 10 mg orally once daily or 25 mg orally every other day as a maintenance protocol. Treatment with acitretin leads to decreased plaque thickness, scaling, and pruritis. However, there is not much reduction in body surface area (BSA).

In combination with phototherapy, dosing is recommended at 25 mg orally once daily for two weeks before phototherapy, with a need to decrease the initial dose of ultraviolet (UV) light. If a patient is already on a stable dose of UV light and is starting acitretin, reduce the dose by 30% to 50% approximately seven days after initiation of acitretin.

Specific Patients Population 

• Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. However, the use of acitretin is contraindicated in patients with severe hepatic impairment.

• Patient with Renal Impairment: A 53 % reduction of acitretin plasma concentrations was observed in patients with end-stage renal disease. The drug was not able to be removed by hemodialysis in these subjects.

• Pregnant Women: It is considered a pregnancy category X medicine. As per the box warning, acitretin must not be given to pregnant patients, patients who intend to become pregnant during therapy, or at least three years following discontinuation of treatment. Significant human fetal abnormalities have been reported with the administration of acitretin.

• Breastfeeding Women: Due to the potential for serious adverse reactions to infants, the manufacturer recommends avoiding acitretin in nursing mothers as the drug presents in breast milk.[7]

• Pediatric Patients: The safety and efficacy of acitretin are not established for pediatric patients.

• Geriatric Patients: In a multiple-dose trial, a 2-fold increase in acitretin plasma concentrations were observed in geriatric patients.

Adverse Effects

A high amount of vitamin A produces a wide spectrum of signs and symptoms primarily of the musculoskeletal, mucocutaneous, neuropsychiatric, central nervous systems, and hepatic systems. Many of the adverse reactions reported using acitretin capsules resemble those of the hypervitaminosis A syndrome. Following adverse reactions are reported in clinical trials and post-marketing experience.[8]

Cardiovascular: Flushing, acute myocardial infarction, thromboembolism, stroke

Immune System Disorders: Hypersensitivity, including angioedema and urticaria 

Nervous System: Headache, pain, rigors; myopathy with peripheral neuropathy which improved upon discontinuation of the acitretin.

Psychiatric: Aggressive feelings, depression, insomnia, self-injurious behavior, and/or suicidal thoughts have been reported. Since other factors may have contributed to psychiatric events, it is not known if they are related to acitretin.

Reproductive: Vulvo-vaginitis (due to Candida albicans)

Skin and Appendages: Thinning of the skin, exfoliation of the skin, xeroderma, nail disease, pruritus, erythematous rash, paronychia, particularly on the palms and soles; nail fragility, madarosis, alopecia, paresthesia, hyperesthesia, and exfoliative dermatitis

Vascular Disorders: Capillary leak syndrome

Miscellaneous: xerophthalmia, visual problems, cheilitis, rhinitis, pseudotumor cerebri, tinnitus, and epistaxis, hepatitis

Laboratory Abnormality: Hypercholesterolemia, increased liver enzymes, increased creatinine phosphokinase, hepatotoxicity, hypertriglyceridemia, hyperglycemia, hypoglycemia, reticulocytosis

Contraindications

Absolute Contraindications

• Pregnancy or woman who is likely to become pregnant

• Non-compliance with contraception

• Nursing mothers

Hypersensitivity to drug or components, pregnancy, intent to become pregnant within three years after treatment discontinuation, severe hepatic or renal dysfunction, chronic abnormally elevated blood lipid levels, or concomitant use with methotrexate or tetracyclines.

It is vital that clinicians who prescribe acitretin to women of childbearing age ensure that they do not get pregnant for at least three years after discontinuing the medication. 

United States Boxed Warning

Female patients should abstain from ethanol during therapy and for at least two months after discontinuing treatment.

Caution

• Concomitant administration with methotrexate increases the risk of hepatic adverse effects.

• Concomitant administration with cyclosporine increases the risk of hypertriglyceridemia.

• Acitretin can undergo reverse metabolism to etretinate with acitretin if used in combination with alcohol.[9]

• The use of other vitamin A compounds can lead to hypervitaminosis A-like toxicities.

• The combination of tetracyclines and retinoids can lead to pseudotumor cerebri and should be avoided.

Individuals prescribed acitretin should receive counsel against giving blood donations for at least three years. The drug is known to remain in the blood for a long time, and the risk of genetic defects is high.

Monitoring

• Lipid profile

• Liver function tests[10]

• Complete blood count (CBC)

• Blood glucose in patients with diabetes

• Evaluation of bone abnormalities and visual problems

• Serum pregnancy testing

Toxicity

Acitretin must be withdrawn all at once in case of acute overdosage. Overdose symptoms are similar to acute hypervitaminosis A (headache and vertigo). In both mice and rats, the acute oral toxicity (LD50) of acitretin was only observed at greater than 4,000 mg per kg dose. In one case report of an overdose, a 32-year old adult male patient with Darier’s disease took 525 mg single dose. Later, he has vomited for several hours; however, he did not experience any other ill effects. One case of fulminant hepatic failure following an intentional overdose of 600 mg of acitretin was reported where the patient demonstrated a rapid recovery and did not require liver transplantation. [11] If any female patients of childbearing potential take an overdose of acitretin, a pregnancy test is recommended at the time of overdose and needed to council patient as per box contraindication and warning related to potential birth defects. Also, need to encourage patients to use contraceptives for at least three years’ duration after the overdose.

Enhancing Healthcare Team Outcomes

Acitretin is frequently used to treat several skin disorders, including acne, psoriasis, lichen planus, and discoid lupus. While the drug is effective, it is crucial for interprofessional healthcare team members, including pharmacists, nurse practitioners, PAs, and primary care clinicians, to know its potential adverse effects. Clinicians should never prescribe the drug to a pregnant female because of the risk of teratogenicity. Also, the FDA has issued several boxed warnings about the risk of hepatitis when combining the agent with alcohol or methotrexate. When prescribing acitretin, the patient must understand the potential adverse effects and the importance of avoiding alcohol. [12][13]

Given the warnings, it is apparent that an interprofessional team is the best means to manage acitretin therapy. Once the prescriber has decided to give the patient the drug, nursing can counsel on the patient’s dosing, administration, and the potential teratogenicity if the patient is female. The pharmacist will verify dosing and perform medication reconciliation, alerting the prescriber of any issues. Nursing can also chart the therapeutic progress of the condition treated, so the prescriber can adjust therapy as needed. Through this interprofessional team paradigm, acitretin can deliver maximal benefit with minimal downside, resulting in better patient outcomes. [Level 5]

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References

1.

Ighani A, Partridge ACR, Shear NH, Lynde C, Gulliver WP, Sibbald C, Fleming P. Comparison of Management Guidelines for Moderate-to-Severe Plaque Psoriasis: A Review of Phototherapy, Systemic Therapies, and Biologic Agents. J Cutan Med Surg. 2019 Mar/Apr;23(2):204-221. [PubMed: 30463416]

2.

Skillen LA, Corry A. Combination therapy of sirolimus and acitretin in solid organ transplant recipients: a new cutaneous adverse event. Clin Exp Dermatol. 2019 Jan;44(1):62-63. [PubMed: 30430627]

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Mehrtens SH, de la Hera I, Shankar S. Case of keratoacanthoma centrifugum marginatum treated with acitretin. BMJ Case Rep. 2018 Nov 01;2018 [PMC free article: PMC6214385] [PubMed: 30389737]

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Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic psoriasis therapies. Int J Dermatol. 2019 Jun;58(6):649-658. [PubMed: 30246393]

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Chen W, Zhang X, Zhang W, Peng C, Zhu W, Chen X. Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients. Sci Rep. 2018 Sep 04;8(1):13182. [PMC free article: PMC6123456] [PubMed: 30181619]

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Guenther LC, Kunynetz R, Lynde CW, Sibbald RG, Toole J, Vender R, Zip C. Acitretin Use in Dermatology. J Cutan Med Surg. 2017 Nov/Dec;21(3_suppl):2S-12S. [PubMed: 28952335]

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Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Mar 17, 2021. Acitretin. [PubMed: 30000426]

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Chiricozzi A, Panduri S, Dini V, Tonini A, Gualtieri B, Romanelli M. Optimizing acitretin use in patients with plaque psoriasis. Dermatol Ther. 2017 Mar;30(2) [PubMed: 27998019]

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Grønhøj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol. 2000 Dec;143(6):1164-9. [PubMed: 11122016]

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Sauder MB, Cheung L, Beecker J. Acitretin-induced hepatitis: when to monitor cholestatic enzymes. J Cutan Med Surg. 2015 Mar-Apr;19(2):115-20. [PubMed: 25775629]

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Leithead JA, Simpson KJ, MacGilchrist AJ. Fulminant hepatic failure following overdose of the vitamin A metabolite acitretin. Eur J Gastroenterol Hepatol. 2009 Feb;21(2):230-2. [PubMed: 19092674]

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Ortiz NE, Nijhawan RI, Weinberg JM. Acitretin. Dermatol Ther. 2013 Sep-Oct;26(5):390-9. [PubMed: 24099069]

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Dunn LK, Gaar LR, Yentzer BA, O’Neill JL, Feldman SR. Acitretin in dermatology: a review. J Drugs Dermatol. 2011 Jul;10(7):772-82. [PubMed: 21720660]

Disclosure: Patrick Zito declares no relevant financial relationships with ineligible companies.

Disclosure: Thomas Mazzoni declares no relevant financial relationships with ineligible companies.

Uses, side effects, and interactions

Acitretin is a prescription drug. It is available as an oral capsule. It is used in the treatment of psoriasis.

It is also available as a brand-name drug called Soriatane and as a generic drug.

Share on PinterestAcitretin is an effective treatment for severe psoriasis.

Acitretin belongs to a class of drugs called retinoids. Retinoids relate to retinol, or vitamin A.

Acitretin works by binding to receptors in the body. These receptors help normalize the speed of skin cell growth, reducing the effects of conditions that include psoriasis.

A doctor will likely only prescribe acitretin if other drugs are not effective for a case of psoriasis or if an individual cannot use other psoriasis drugs.

This drug is used on a long-term basis. If prescribed, it is worth calling the pharmacy ahead of time as not all pharmacies stock this item.

The drug is used to treat severe psoriasis.

Psoriasis is a skin condition that causes cells in the outer layer of the skin to grow faster than normal and build upon the surface of the skin. This leads to inflammation and red, thickened areas of skin, often with silvery scales.

Acitretin carries a United States Food and Drug Administration (FDA) black box warning. This is the most serious health warning a drug can carry.

The medication carries the following warnings:

• Severe warning regarding congenital anomalies: Avoid this drug if you are pregnant or planning to become pregnant within three years after stopping this drug. Acitretin can cause severe congenital anomalies. Women who are able to bear children should use effective birth control while on acitretin.
• Liver problems warning: This drug can cause liver problems, include abnormal liver function test results and inflammation. A doctor will run blood tests before prescribing acitretin. These serve to check liver function before and during acitretin treatment.
• Vision problems: This drug can decrease vision in the dark, causing a condition called night blindness that can onset suddenly. Take extreme caution when driving at night while taking acitretin. This condition usually resolves after the course of treatment has drawn to a close.
• Avoid giving blood: Do not donate blood while taking this drug and for at least 3 years after stopping. The presence of acitretin in the blood can harm an unborn baby if given to a woman who is pregnant.
• Depression: This drug may cause depression or aggressive behavior, including self-harming urges. Call a doctor right away if these urges occur. The doctor may recommend a medication change.

Side effects that can occur when taking acitretin include:

• chapped lips
• peeling fingertips, palms, and soles of the feet
• itching
• scaly skin all over your body
• weak nails
• sticky or fragile skin
• runny or dry nose
• nosebleeds
• dry mouth
• joint pain
• tight muscles
• hair loss
• dry eyes
• high cholesterol
• drowsiness

The drug can also lead to serious complications in people that may already have a predisposition towards them, including:

• liver problems
• heart attack
• stroke
• serious skin conditions
• vision problems
• pancreatitis
• blood vessel issues
• high pressure on the brain
• depression
• abnormal muscle or bone changes
• high blood sugar levels

People with the following conditions should completely avoid this drug:

• severe liver and kidney disease
• high cholesterol
• allergy to retinoids or acitretin

Acitretin can interact with other drugs and chemicals in the body to create adverse effects. It is important to know what to take and avoid when on a course of acitretin.

This drug is known to increase the risk of congenital abnormalities, and alcohol can further enhance the duration of this risk to beyond 3 years after stopping acitretin. Avoid alcohol at all costs while taking acitretin.

There are several types of medication to avoid while taking acitretin, including:

• Tetracycline antibiotics: These increase the risk of dangerous pressure levels in the brain.
• Methotrexate: Taking this drug alongside acitretin can greatly increase the risk of liver problems.
• Progestin-only birth control pills, or minipills: Acitretin can reduce the effectiveness of minipills, and it is vital not to become pregnant while taking acitretin. A doctor may stop the minipill and prescribe a different method of birth control.
• Phenytoin: Acitretin can enhance the side effects of phenytoin, including slurred speech, confusion, and coordination or balance problems.
• Vitamin A supplements and other oral retinoids: Taking these drugs with acitretin may cause nausea, vomiting, loss of balance, and blurry vision.

Acitretin is available in its generic form in 10-milligram (mg) and as the brand-name drug Soriatane in 10-milligram (mg), 17.5-mg, 22.5-mg, and 25-mg capsules.

A typical starting dose is around 25 to 50 mg once per day, to be taken with the largest meal. The doctor who prescribed the drug will monitor the reaction to this dosage and make changes if side effects are becoming disruptive.

There is no dosage recommended for children under 18 years of age, as they should not take the medication. Adults over the age of 65 years will often start on a lower dose.

If a dose is accidentally missed, do not take a double dose next time. It is vital never to miss a dose, as this can reduce or block the effectiveness of the drug.

Here are several extra considerations to bear in mind when transporting, acquiring, or storing acitretin:

• Always take acitretin with food.
• Always carry the medication on your person. When flying, never put it into a checked bag but keep it in the carry-on luggage.
• Airport x-ray machines will not damage the medication.
• Always carry the original prescription-labeled box, as airport security may wish to see this.
• Avoid putting medication in the glove compartment of a vehicle or leaving it in the car. Be sure to avoid doing this in extreme temperatures.
• Many insurers require pre-authorization before approving this treatment. Contact your insurer ahead of time.
• Wear protective clothing in the sun, as acitretin makes the skin more sensitive.
• Prescriptions for acitretin are not refillable.

Retinol: application, effect, tips for use – Ingredients – Blog

We are used to the fact that most of the ingredients in the composition of cosmetics perform one function well: some moisturize, others relieve irritation, others promote renewal. But this rule does not apply to retinol – it masterfully copes with almost any problem, if you find the right approach to it. Anti-aging effect, reduction of pore relief, fight against rashes, lightening pigmentation, stimulation of renewal, increase in elasticity … A solid list, right?

Like other substances with a powerful active effect, it has its own characteristics. To begin with, the first time you use it, the skin condition may visually worsen before you see the first positive results. The most important thing here is not to stop halfway, but to continue the course of treatment / care. In addition, as part of cosmetics, this component is available in various forms and concentrations, so if an undesirable reaction occurs, it is easy to choose another option.

What is retinol?

Retinol is a form of vitamin A (however, the same name is often used as a general term for all vitamin A derivatives – retinoids).

This component has long been successfully used in cosmetics designed to correct age-related changes:

• wrinkles;
• tissue density reduction;
• age spots;
• uneven terrain;
• roughness and roughness;
• dullness, loss of radiance.

In addition, it is used in the treatment of acne and to get rid of post-acne marks.

What effect does it have on the skin?

• Smoothes the texture. Research shows that the natural process of skin cell renewal slows down after age 25. Retinol brings it back to optimal levels, helping to restore freshness, smoothness and even tone.
• Fights wrinkles. Retinol stimulates the production of collagen and elastin, which, in turn, fill wrinkles, smooth creases and restore elasticity.
• Clears pores. On oily and problematic skin, retinol will show itself as an effective assistant in the fight against rashes. It balances sebum production, preventing clogged pores and inflammation.

How does it work?

Penetrating deep into the skin, retinol stimulates the formation of new cells and restores connective tissues. Using it for the first time, you will most likely go through a process called retination, characterized by redness and intense flaking. By applying a product with retinol to your face, you force the cells to reorganize to work in a new mode, which implies accelerated renewal. This happens gradually, adaptation can take some time – usually up to 4 weeks.

In general, flaking and redness on first use is completely normal. If they are not accompanied by itching and burning, you should not immediately abandon the new care, just wait until the body “gets used” to it. However, if the symptoms do not disappear after 28 days of use, this is a reason to contact a cosmetologist or dermatologist in order to select an alternative form or dosage of the ingredient.

How to use it correctly?

In order to make the adaptation process comfortable, in the case of this active ingredient, the rule of “less is more” should be followed.

1. For the first acquaintance, it is recommended to choose a product with a low concentration.
2. Apply a small amount of product (pea size) at night a couple of times a week to see how tolerant you are. The action of retinoids persists for 72 hours.
3. If the skin reacts positively to the new ingredient, you can gradually increase the frequency of use and concentration. In case of severe irritation, on the contrary, it is recommended to reduce it – for example, by mixing it with a fat cream.

There is a concept of “retinol ladder”, which implies a gradual increase in regularity:

• 1-2 weeks – every three days,
• 3-4 weeks – every two days,
• From 5 weeks – every day.

Retinol can be applied all over the face, however it is recommended to avoid the lash line when used around the eyes.

What kind of skin is it suitable for?

Due to its broad spectrum of action, this ingredient is suitable for all skin types, however, the degree of sensitivity must be taken into account: skin prone to irritation requires special care in terms of frequency of use and concentration.

You can start using retinol to fight the first age-related changes (and prevent them) as early as 25 years old.

When will the result be noticeable?

It depends on the concentration, frequency of application and individual characteristics. The first improvements can be seen after just a few applications: at the end of the retinization period, the face becomes smoother, the tone evens out, and the pores are cleared.

If you have chosen this component for skin rejuvenation, keep in mind that the process will be quite lengthy. However, patience pays off: with regular, long-term use, retinol significantly increases the level of collagen in the skin, improving its density in deep layers and preventing the appearance of new wrinkles.

Studies show that wrinkle reduction is observed in most patients after 3 months, and with longer use, the condition continues to improve. So, after 6 months, a sufficient amount of collagen and elastin accumulates in the skin in order to gradually begin to fill in existing wrinkles, and dark spots lighten due to accelerated renewal.

Types and uses

Depending on the molecular structure and time of the first synthesis, retinoids are divided into generations. Substances similar in structure to the vitamin A molecule, called non-aromatic, got into the first generation, monoaromatic compounds into the second, polyaromatic compounds into the third, and, finally, the fourth generation combined pyranones.

Topical retinoids

Topical retinoids are included in topical formulations. Most often, first-generation retinoids are found in this format – the most studied and “predictable”.

To be effective on the skin, any form of vitamin A must be converted to retinoic acid (tretinoin) by its enzymes. So, the closer the molecule of the active substance in structure to the tretinoin molecule, the stronger the effect.

Consider the form of vitamin A, retinyl palmitate: under the influence of enzymes, it is first converted to retinol, then to retinaldehyde, and only then to tretinoin. The effect of a drug with retinyl palmitate will be less active than, for example, a drug with tretinoin that does not require conversion.

On the other hand, the more active the substance, the greater the likelihood of side effects. When choosing between different ingredients, the level of skin sensitivity should be taken into account: in many cases, a long transducer chain is more of a plus than a minus. Yes, the result will not be so fast, but with a high probability the retinization process will go smoothly and smoothly.

Let’s take a closer look at common forms:

Tretinoin. Used in pharmaceutical and professional products to combat acne, hyperpigmentation and hyperkeratosis.

Triple Power Night Multi-Acid Concentrate Lotion, 120 ml

Multifunctional lotion

8060 ₽

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Triple Power Overnight Cream, 50 ml

Effectively restores the protective barriers of the skin

8036 ₽

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Triple Power Brightening Serum, 30 ml

Evens tone, stimulates metabolic processes

8834 ₽

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Retinaldehyde (Retinal). Popular in cosmetics. In the chain of transformations, it is one step ahead of tretinoin. It has good efficiency already at a concentration of 0.025-0.05%, but due to possible instability it is somewhat less common in cosmetic products than other forms.

Anti-aging cream-gel, 50 ml

Prevents the appearance of wrinkles, improves skin firmness and elasticity

6149 ₽
-10%
6832 ₽

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Anti-aging serum, 30 ml

Models the oval of the face, has a moisturizing and revitalizing effect

6149 ₽
-10%
6832 ₽

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Retinol Lift wrinkle smoothing capsules, 10 pcs

INTENSIVE REJUVENATING ANTI-AGE CARE

1585 ₽

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Retinol. The most common retinoid, relatively inexpensive, but effective. For stabilization, it is often found in an encapsulated form: the molecules of the active substance are enclosed in capsules that prevent contact with other components in the composition of the product and are absorbed only when passing through the lipid layer.

Retinol Pure Serum, 30 ml

Powerful regenerating and lifting effect

7057 ₽

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1

Intense Concentrated Anti-Aging Eye Care, 15 ml

AGAINST WRINKLES, BAGS AND DARK CIRCLES UNDER THE EYES

2550 ₽
-20%
3187 ₽

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Restoring Cream, 50 ml

INTENSIVE RESTORATION AND RENEWAL OF THE EPIDERMIS

4060 ₽
-10%
4511 ₽

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Retinyl Palmitate. Ester of retinoic acid, which has a very gentle effect. In cosmetics, this component is most often found as an antioxidant at a concentration of about 0.5-2%, and for a pronounced effect (at the level of retinol) a sufficiently high concentration is required.

Multi-Action Serum, 150 ml

intensive care for aging skin

1318 ₽
-thirty%
1882 ₽

Receipt expected

Intensive anti-deep wrinkle serum, to even out complexion and skin texture B3, 30 ml

Intensive anti-ageing serum

3152 ₽
-20%
3939 ₽

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Systemic retinoids

Systemic retinoids are used for internal use in the complex therapy of skin diseases. The most common ones are:

Isotretinoin. It is used to combat moderate to severe acne (as part of such medical products as Roaccutane, Accutane and Acnecutane) and is considered the only drug that cures acne. It affects all the factors that cause the disease: the production of sebum, clogged pores and the growth of bacteria.

As with topical retinoids, isotretinoin often causes skin deterioration in the first weeks of treatment followed by gradual recovery. In addition to the period of exacerbation, isotretinoin has other possible side effects (for example, the development of depression, inflammatory bowel disease), so treatment should be carried out strictly under the supervision of a physician. During pregnancy, use is strictly prohibited.

It is important to follow the dosage prescribed by the medical specialist and continue the prescribed course of treatment even after the disappearance of external imperfections.

Acitretin and Etretinate. Retinoids of the second generation are prescribed for various types of psoriasis, impaired keratinization (as part of Tigazon and Neotigazon preparations). They inhibit the growth of cells in the outer layers of the skin and stabilize its cellular structure, helping to cope with peeling.

As in the case of isotretinoin, treatment should be carried out strictly under the supervision of a physician and is strictly not allowed during pregnancy.

Retinol can be a powerful help in solving many problems: from acne and enlarged pores to wrinkles, loss of elasticity and age spots. Although its action is well studied, it can behave completely differently on different skin, so the selection of a suitable remedy must be left to specialists, especially when it comes to systemic use.

Contact a cosmetologist or dermatologist to draw up a system and schedule of care: based on your needs and needs, the doctor will be able to choose a convenient form and give recommendations for use – you just have to observe the pleasant changes and enjoy the effect!

Author – Marina Kanukhina

Modern possibilities of systemic therapy of psoriasis

Currently, most scientists consider psoriasis as a systemic immune-associated disease with a dominant role in its development of genetic factors [1]. Genetic predisposition ( PSORS1; HLA Cw6, B13, B17, B27 ), the impact of environmental, humoral and cellular factors form pathological immune responses that cause a chronic inflammatory process in the skin and the body as a whole [2, 3].

Systemic inflammation in psoriasis is associated with the activity of T-lymphocytes and antigen-presenting cells, which produce a wide range of pro-inflammatory cytokines and chemokines. The successful use of anticytokine therapy in patients with psoriasis confirms the role of the immune system in the pathogenesis of dermatosis [4, 5].

The most common diseases and conditions pathogenetically associated with psoriasis are arterial hypertension, metabolic syndrome, type 2 diabetes mellitus, fatty liver disease. Psoriasis has been found to have the strongest association with metabolic syndrome among all skin diseases. It is possible that common genetic mechanisms contribute to the development of psoriasis and metabolic syndrome. Patients with psoriasis have a high prevalence of metabolic syndrome as a leading risk factor for cardiovascular disease. The research results suggest that the relationship of psoriasis with the above pathology can lead to an increase in early mortality and an even more pronounced decrease in the quality of life. Much attention should be paid to the functional state of the hepatobiliary system, since studies in this area have revealed significant changes in liver function in severe and torpid forms of dermatosis [6, 7].

Multifactorial etiology of psoriasis, systemic pathological processes, serious comorbidities, psychological state of patients, reduced quality of life often cause difficulties in the selection of therapy regimens. The choice of therapeutic method should depend on the presence of concomitant diseases, since in some cases the use of standard methods of treatment can harm the patient, many patients stop taking the drug due to intolerance and concerns about the safety profile. All of the above determines the need for a wider introduction into clinical practice of drugs for systemic therapy of psoriasis with a high safety profile [8].

A new class of therapeutic agents for the treatment of psoriasis, called “small molecules”, which are selective inhibitors of signaling pathways, have been developed to date. One of the representatives of this group of drugs is apremilast, a low molecular weight inhibitor of phosphodiesterase type 4 (PDE4) in inflammatory cells [9, 10].

PDE4 specifically targets cyclic adenosine monophosphate (cAMP) in inflammatory cells, including macrophages, monocytes, mast, dendritic cells, eosinophils, and T cells. The mechanism of action of apremilast is based on the inhibition of PDE4, which blocks the degradation of cAMP inside the cell. And an increase in the level of intracellular cAMP, in turn, suppresses the production of pro-inflammatory cytokines (for example, TNF-α, IFN-γ, IL-2, IL-12 and IL-23), which play a major role in the pathogenesis of dermatosis, and stimulates the production of anti-inflammatory cytokines (IL -6 and IL-10), which is pathogenetically substantiated in psoriasis [11, 12].

The aim of this study was to analyze the clinical efficacy and safety of systemic therapy for psoriasis using apremilast.

Material and methods

As a result of screening, 7 patients (5 men and 2 women) with moderate psoriasis aged 22 to 63 years (mean age 39.28±3.73 years) were included in the study. The average duration of the disease was 16.71±2.39 years.

To assess the severity of the pathological skin process, the dynamics of the course of the disease and the effectiveness of therapy in patients with psoriasis, we used the Psoriasis Area and Severity Index (PASI), the Body Surface Area Index (BSA), a global assessment researcher (Investigator’s Global Assessment; IGA). Itching was assessed using a numerical rating scale (10-cm scale; Numerical Rating Scale; NRS), a visual analog pain scale (VAS) was used to assess the activity of psoriatic arthritis. Dermatology Life Quality Index (DLQI) was used to assess the degree of negative impact of dermatosis on various aspects of a patient’s life.

Results

According to the clinical examination and assessment of the severity of clinical manifestations, before treatment, the average values ​​of the PASI index in the general group of patients were 25.27±3.64; BSA index — 12.78±1.84; IGA — 3.0±0.43; itching intensity (10 cm scale) — 5.85±0.84; VAS score — 4.28±0.61; number of painful joints — 7.28±1.04; number of swollen joints — 1.85±0.26; DLQI index — 14.57±2.09.

Due to the presence of moderate severity of psoriasis, a decrease in quality of life and resistance to previous therapy, patients were prescribed systemic therapy using the drug apremilast as monotherapy according to the standard scheme with a preliminary dose titration (Table 1). Table 1. Dose titration scheme

An objective assessment of the severity of the psoriatic process after 14 weeks of therapy showed a positive dynamics of the process in the general group of patients: the average values ​​of the PASI index were 9. 02±1.29; BSA index — 6.92±0.99; IGA score — 1.71±0.24; itching intensity (10 cm scale) — 2.42±0.34; VAS score — 2.14±0.31; number of painful joints — 2.72±0.39; the number of swollen joints was 0 (Table 2). Table 2. Comparative assessment of the severity of the psoriatic process during treatment with apremilast for 14 weeks

An objective assessment of the severity of the psoriatic process after 26 weeks of therapy also showed a positive dynamics of the process in the general group of patients: the average values ​​of the PASI index were 3.91±0.56; BSA index — 3.57±0.51; IGA score — 0.93±0.13; itching intensity (10 cm scale) — 1.35±0.19; VAS score — 1.71±0.24; number of painful joints — 2.72±0.39; number of swollen joints – 0; DLQI index — 3.71±0.53 (Table 3). Table 3. Comparative assessment of the severity of the psoriatic process during treatment with apremilast for 26 weeks

Thus, against the background of monotherapy with apremilast for 26 weeks, all 7 patients showed positive dynamics of the psoriatic process in the general group of patients: the average values ​​of the PASI index decreased by 85%; BSA index – by 72%; IGA score – by 69%; the intensity of itching (10-cm scale) – by 77%; VAS score — by 60%; the number of painful joints – by 63%; the number of swollen joints – by 100%; DLQI index – by 75%.

During the general clinical examination of patients throughout the entire period of taking apremilast, no clinically significant deviations in the results of laboratory tests were detected. Patients noted good tolerability of the drug. Three people had adverse events that manifested as mild dyspeptic disorders (nausea) in the early stages of taking the drug (the first 2 weeks), which resolved within 1-2 hours after taking the tablets.

Talk

Despite the fact that the arsenal of existing treatments for patients with psoriasis is currently quite wide, the problem of improving methods of treating dermatosis remains relevant to this day. Safety is one of the unmet needs in the treatment of the disease, since psoriasis is not only a skin disease, but also a systemic pathology, accompanied by polymorbidity in diseases of the internal organs and deviations in the psychosocial sphere [13].

The results of numerous studies suggest that the relationship of psoriasis with comorbidities such as cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome and obesity may lead to an even more pronounced decrease in the quality of life and an increase in early mortality [14] .

Various comorbid conditions have a significant impact on the tactical choice of therapy for psoriasis. Standard methods of treating dermatosis often present difficulties, since long-term use can contribute to the development of adverse events, worsening the course of concomitant pathology and require constant laboratory monitoring [15].

In addition to eliminating the inflammatory process in psoriasis, dermatosis therapy should also be aimed at prolonging remission and preventing the development of comorbid conditions [16].

According to international and domestic recommendations, the main systemic therapeutic agents for severe psoriasis are synthetic retinoids, cytostatic and biological drugs. However, with their long-term use, a high level of adverse events is often noted. For example, cyclosporine has hepatotoxicity and nephrotoxicity, and the use of this drug can lead to the development of arterial hypertension, impaired glucose tolerance, contribute to the onset of dyslipidemia, as a result of which cyclosporine is contraindicated in patients with metabolic syndrome and reduced renal function. Acitretin is hepatotoxic and may cause or worsen hypercholesterolemia or hypertriglyceridemia. Methotrexate and acitretin have a proven teratogenic effect, so they are used with caution in women of reproductive age. Methotrexate is also contraindicated in patients with alcohol dependence or chronic liver failure [17, 18].

Monoclonal antibody preparations are better tolerated with long-term therapy, but the main problem with biologics is an increased risk of infection, as well as the development of resistance, which can lead to a decrease in their clinical effectiveness in the long term. These drugs also cannot be used in patients with psoriasis on the background of multiple sclerosis and in the presence of other demyelinating diseases, in most cases during pregnancy and lactation, and with caution in patients with congestive heart failure [19].

In numerous studies, apremilast has demonstrated not only effective elimination of inflammation, a significant reduction in the number of immune cells that infiltrate the dermis and epidermis during psoriatic process, but also a favorable safety profile and good tolerability [20].

The safety of apremilast and the low risk of drug interactions allow it to be used for the treatment of psoriasis in the elderly, as well as those suffering, in addition to dermatosis, with concomitant diseases of the cardiovascular system, metabolic syndrome, and diabetes mellitus [21].

Obtained data from an observational study indicate that the use of apremilast helps to reduce inflammation in psoriatic skin lesions, the drug is an effective treatment for patients with moderate and severe plaque psoriasis and psoriatic arthritis. It was found that apremilast therapy is quite simple and convenient for patients: there is no need for constant monitoring of laboratory parameters, examinations to detect latent forms of tuberculosis, there is no risk of toxic effects on target organs, it is enough to follow current clinical guidelines for managing patients. The drug has gained recognition among patients for its convenient oral form [22].

Terminals

• Monotherapy with apremilast has been proven effective in the treatment of plaque psoriasis and psoriatic arthritis;

• a favorable safety profile and tolerability of apremilast therapy was stated;

• improved psychological state and improved quality of life.

Author contributions:

Research concept and design — Yu.N. Perlamutrov, T.V. Aivazova

Collection and processing of material – T.V. Aivazova, K.B. Olkhovskaya, A.M. Solovyov

Statistical data processing – T.V. Aivazova, K.B. Olkhovskaya, A.M. Solovyov

Text writing – T.V. Aivazova

Editing – Yu.N. Perlamutrov

Authors’ contributions:

The concept and design of the study – Yu.N. Perlamutrov, T.V. Aivazova

Collecting and interpreting the data – T.V. Aivazova, K.B. Olkhovskaya, A.M. Soloviev

Statistical analysis – T.V. Aivazova, K.B. Olkhovskaya, A.M. Soloviev

Drafting the manuscript – T.V. Aivazova

Revising the manuscript – Yu.N. Perlamutrov

Credits

HOW TO QUOTE:

Perlamutrov Yu.N., Aivazova T.V., Olkhovskaya K.B., Solovyov A.M. Modern possibilities of systemic therapy of psoriasis.