PSORIASIS: Causes and treatments

Psoriasis is a chronic skin disease that occurs in about 1% of the population and affects both sexes equally. It can occur at any age but over 70% of cases do so before age 30.

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    It typically appears as red circular and scaly lesions that can become very itchy. This disease has outbreaks. There are periods in which the disease aggravates and periods in which it is more controlled. There is no cure for this disease. The patient must focus on keeping the disease in check to prevent recurrences.

    Why is it produced?

    It has been shown that psoriasis has a certain genetic susceptibility. If one parent has it, the risk of their offspring to get it is 10%. If both parents suffer from this disease there is a 40% chance that their children will have it as well.

    Over this genetic belief, certain infections may develop like streptococci, staphylococci, candida, trauma (Koebner Phenomenon). Also, some drugs such as β-blockers, lithium, antimalarials and certain antihypertensives, and stress can become triggers.

    Symptoms

    The lesion is characterized as a red scaling plate, which can sometimes be very pronounced. These lesions may have different sizes. From very small (guttate psoriasis), to very large and confluent (psoriatic erythroderma) which occur when psoriasis affects more than 90% of the skin.

    There are several types of psoriasis:

    • Guttate psoriasis: It usually presents as small plates between 2-5 mm in diameter, affecting both the trunk and limbs. There may also be lesions on the scalp. Usually affects young people and often produces tonsillitis or a toxicodermia (drug induced cutaneous reactions).
    • Psoriasis in small and large plates (“vulgar psoriasis”) : is the most common clinical form of psoriasis and is usually chronic with continuous outbreaks. The plates may be small, less than 3 cm, or larger. They are red, circular and may flake a lot. Appears on elbows, knees, scalp (especially behind the ears), back and navel.
    • Erythroderma: means when there is an involvement of more than 90% of the skin. It may appear suddenly or progress from a previous psoriasis. It is a serious condition that requires hospitalization.
    • Pustule forms: Some patients may have lesions with pus inside (pustules); either localized, for example, only on the palms or on the palms and soles of the feet. However, it may affect different areas of the skin.

     

    Where does Psoriasis develop?

    • Psoriasis of the skin folds (inverse psoriasis). Sometimes psoriasis may affect the folds (especially on armpits and buttocks). The lesions in these locations are different from the rest of the skin, characterized by red, moist lesions with sharp edges and no flaking.
    • Psoriasis of the scalp. On this location psoriasis develops as a very rich, pearly peeling forming a thick layer which can sometimes cross the hairline and become visible.
    • Psoriasis of the nails. Often psoriasis affects the nails. The most characteristic feature is the presence of small holes in several nails as if it was done with a pin (“pitting”). It is also common to find a whitish discoloration on the edge of the nail (leukonychia) and also a characteristic lesion called “oil stain” which is a salmon colored stain lining the whitish discoloration. Rare, but possible is the thickening of the end of the nail.
    • Palmo Plantar Psoriasis. There may be a lot of scaling and deep fissures and/or swelling may develop on the fingertips (pulpitis).

    Treatment for Psoriasis

    Psoriasis is a chronic disease so there is no curative treatment. The objective is to try to prevent outbreaks.

    Generally, the type of treatment depends on the severity of Psoriasis. When there is a mild psoriasis, topical treatment is used, mainly corticosteroid creams and / or vitamin D derivative (calcipotriol and tacalcitol).

    For moderate and severe Psoriasis more potent treatments such as phototherapy or systemic treatments are used. Acitretin (a derivative of vitamin A) and also immune-suppressants such as methotrexate and cyclosporin A. Recently, more specific immune treatments so-called “biological therapy” are used. They are synthesized by biotechnology and are used for severe cases that were not able to be controlled with systemic therapy.

    How to prevent Psoriasis?

    To prevent outbreaks early treatment of infections (especially tonsillitis) is recommended. Trauma due to scratching must be avoided, as these traumas can lead to the appearance of new lesions. It is also recommended to avoid stress and certain drugs such as lithium, beta-blockers, antimalarials, NSAIDs and systemic corticosteroids. Between outbreaks, as maintenance therapy, it is recommended to keep the skin hydrated by applying moisturizers on a daily basis. In some cases it is necessary to apply creams without corticosteroid, such as vitamin D derivatives to keep the disease under control.

    Etiopathogenesis

    Skin cells shed rapidly due to cell hyper proliferation.

    Psoriasis is mediated by immune mechanisms with a genetic base. There are also environmental factors involved. Excessive inflammatory response by several mediators such as TNF-alpha occurs. There are different types of triggers:

    • Physicists such as trauma
    • Viral or bacterial infections
    • Medication: beta blockers, ACE inhibitors, lithium, antimalarials among others
    • Emotional stress

    Types of Psoriasis

    • Vulgar
    • Gutatta
    • Facial
    • Erythrodermic
    • Facial
    • Nail
    • Scalp
    • Arthropathic

    Evolution

    It is a chronic disease for which there is no cure, but there are periods of remission.

    Patients go through outbreaks and stability phases. Outbreaks typically affect the self-esteem of most patients.

    My experience with the disease

    Psoriasis is one of the conditions in which I have invested more effort and dedication.

    Until recently dermatologists had the perception that we could not do much against a dermatosis that responded poorly to topical and systemic treatments, and had an unpredictable course. Patients felt hopeless, as if it were a biblical disease.

    In my years of residence in Dermatology, during a vacation in London, I had the opportunity to learn about a treatment that offered satisfactory results known as Goekerman. It consists of applying a tar (mineral) and radiate with UVB (311 nm). Upon my return, I convinced the professor of the Clinical Hospital of Barcelona, Professor Piñol Aguadé, and my father, who had his office in Corachán Clinic, that we should introduce this treatment in our country. So the first lamps were imported to Spain.

    At this time photobiology began in Dermatology; in fact, a few years after the photochemotherapy or PUVA was introduced, which consisted of associating the wall with oral psoralens and using long length (230 nm) radiation. This treatment achieved unprecedented results and extensive recalcitrant psoriasis.

    As part of my training, I was also at the Mayo Clinic in U.S.A. Upon my return to Barcelona another promising treatment was introduced; oral retinoids derived from vitamin A.

    I formed a Psoriasis unit at the Sagrat Cor Hospital in Barcelona, whose treatments were mostly outpatient and together with the Hospital of Sant Pau, we became the pioneers in Spain in puva therapy (therapeutic modality using long wave UV Rays).

    The equipment required for this treatment is very costly such as the German Waldman Cabins. New models continue to be developed with different wavelengths, such as ultraviolet narrowband UV-B radiation. Unlike classical PUVA, the puva therapy (psoriasis) does not require administration of psoralens being a significant advantage. For instance, it does not require eye protection against ultraviolet rays during the day and does not produce digestive discomfort.

    Topical treatments remain the first choice for localized psoriasis. Today they have been discovering new molecules, such as derivatives of vitamin D, potent corticosteroids or biological immunomodulators (tacrolimus), that are able to clear stubborn areas such as the scalp, nails, etc.

    In these cases, our collaborators and we prescribe customized topical formulations in which we associate various active ingredients that enhance its effectiveness compared with commercial formulas. The difference is because commercial formulas use very rigid excipients and only one active principle, which reduce the efficiency on certain locations such as the scalp, nails, elbows, knees, etc.

    Today we know that this is a chronic inflammatory disease of autoimmune etiology. Before we only knew part of the mechanism: the keratinocyte hyperproliferation and impaired epidermal differentiation. So we administered Methotrexate (antiproliferative cytostatic) and were getting effective results even though by then we were unaware that T lymphocytes, macrophages and different cytokines (ILK) are the main actors of the pathophysiology of the disease. Psoriasis and other autoimmune diseases benefit from biological treatments that inhibit cytokines (TNF-alpha) or monoclonal antibodies that act in other interleukin cells.

    Currently the available drugs for systemic treatments are methotrexate, cyclosporine A, retinoids, photochemotherapy (PUVA) and new biological agents. Each has its indications and contraindications.

    Treatment Options

    The objective is not only to clear the area in the shortest time avoiding possible side effects, but also in keeping the patient under control over an extended period of time without suffering from the disease.

    Therapeutic Strategy

    Today there is no cure for psoriasis. So our goal is to keep the disease in remission. The type of treatment is decided according to the size, location and general condition of the patient.

    Our residents and employees have protocols on how these drugs should be used. Below is a summary of these protocols.

    Before using a systemic treatment, we usually begin with classic treatments we know best: topical retinoid treatment, puva therapy, methotrexate and cyclosporine.

    “I distrust new medications on the market. I use medications that have been on the market for at least two years so that there is enough evidence of having advantages over those previously used”.

    Topical treatments

    Topical corticosteroids are one of the most effective treatments, if used correctly. They have different strengths and are often used in combination with other active ingredients, to multiply their effectiveness and reduce side effects.

    “Patients should not be afraid to use topical corticosteroids. They are essential in treating the early stages of multiple dermatosis and if administered correctly by a specialist it should not produce side effects.”

    Topical corticosteroids may be associated with derivatives of vitamin D3. The skin is an organ metabolically active and can synthesize this vitamin along with ultraviolet radiation. There are vitamin D receptors in the skin.

    Derivatives of vitamin D significantly improve psoriatic lesions since they inhibit keratinocyte proliferation. The most effective ones are analogs such as tacalcitol and calcitriol.

    Systemic Treatments

    Retinoids + topical treatment

    Psoriasis patients have dry skin and suffer from water loss. Therefore it is important to moisturize the skin.

    I recommend emollient oils or moisturizers without synthetic ingredients made for sensitive skin, followed by an emollient cream. I often use custom design formulations tailored to the patient’s specific needs. The formula may be an ointment, a cream, a gel, a lotion or an aerosol. May contain 2-10% urea, kola extract, aloe vera, salicylic acid, propylene glycol, corticosteroids, and derivatives of vitamin D.

    By administering oral retinoids or acid-acitretino 13 retinoico- cis along with a topical treatment we can expect to get a better response than administering them separately.

    Photochemotherapy: PUVA

    It is associated with the administration of psoralens 8 MOP or 5 MOP taken orally 2 hours before exposure to UVA, topically ½ hour before or by the use of suppositories to avoid possible digestive problems.A series of requirements must be followed such as the energy level to be administered and the ocular protection from sunlight to be used among other conditions. Results are usually achieved with two weekly sessions for a period of 5-7 weeks.

    Action mechanism: Act by forming photoactive dimers in which after irradiation cells are eliminated with suitable results for psoriatic cells: mutagenicity (interacts with DNA), immunosuppressive and antiproliferative action.

    Repuva

    Involves the administration of oral retinoids 10 days prior to treatment with PUVA and during treatment obtaining better results in less time than with PUVA therapy. As with other treatments, a series of recommendations must be followed.

    Narrow UVB Band

    This light spectrum is the most effective for psoriasis achieving similar results to PUVA therapy with additional advantages:

    • Does not require administration of psoralens
    • The narrowband radiation may be used in pregnant women and children. It can also be combined with oral retinoids for better results.

    Methotrexate

    [Protocol prepared by: Dr. V. Expósito, Dr. M. Sánchez Regaña, Dra. Maribel Iglesias, Prof. Pau Umbert]

    Necessary information from each patient.

    Liver disease

    Kidney Disease

    Gastroduodenal ulcer

    Colitis

    Arthropathy

    Alcohol

    Drugs that patients might take may interact with treatment by increasing the toxicity of methotrexate or reduce renal elimination.

    reduce renal elimination.

    Administration and Dosage

    Initial dose: 5 mg with CBC before and within the next 7 days.

    Maximum dose: 0.5 mg / kg (approximately 20-30 mg)

    Weekly doses 5-15 mg v.o. and 25-30 mg i.m.

    Taking medications orally, intramuscular or subcutaneously are equally effective.

    Results may be seen in the first 7-14 days; however best results take between 4-8 weeks, although generalized pustular psoriasis may respond in 24 hours.

    Results may be seen in the first 7-14 days; however best results take between 4-8 weeks, although generalized pustular psoriasis may respond in 24 hours.

    Folinic acid is effective if there is an MTX overdose because it reduces the absorption of dihydrofolate induced by MTX interfering in its effectiveness. Folic acid is recommended 24 hours after methotrexate administration, 1 mg / day or 5-7mg / week to reduce methotrexate toxicity.

    Side Effects

    Some patients have mild discomfort within 24 hours of taking the medication, but in general the side effects are less frequent.

    Patient follow-up

    Blood tests are taken: before treatment, seven days after starting treatment and 4-6 weeks thereafter: CBC, B12 and folic acid, urea, creatinine, transaminases, alkaline phosphatase, total bilirubin, albumin (or protein) serology hepatitis B and C (first time) and terminal peptide of procollagen III (nonspecific marker of liver fibrosis, not isolated but useful increase. Progressive elevation. Risk when above 4).

    Preferably creatinine clearance or glomerular filtration rate: annual.

    Chest x-ray: At beginning of treatment and annually.

    Hepatic ultrasonography: every 3-4 months to see if there are any fibrosis fatty changes. If there is a change, a liver biopsy is done.

    Liver biopsy (1/1000 bleeding risk and risk of death 1/10000):

    Liver ultrasound (fibrosis, fatty changes).

    Elevated transaminases (hepatic enzymes) (5 from 9 or 6 from 12 annual high determinations).

    1,5 g of methotrexate accumulated.

    .

    Ciclosporina

    [Protocolo preparado por: Dr. Manuel Sánchez Regaña, Dr. Cristian Fischer Levancini, Prof. Pablo Umbert – Servicio de Dermatología del Hospital Sagrat Cor. Universidad de Barcelona]

    Mecanismo de acción

    Péptido cíclico lipofílico que se aísla de los hongos. Inhibe, de forma dosis dependiente, la síntesis y acción de los linfocitos T helper, no tanto de los T supresores ni de otras células como los linfocitos B o células NK, ello lo diferencia de otros inmunosupresores. Interfiere en la síntesis de interleukina 2. No altera la síntesis de glóbulos rojos ni plaquetas. No produce toxicidad medular. Puede utilizarse durante el embarazo.

    Farmacocinética

    La ciclosporina (SANDIMUN NEORAL) se presenta en forma de cápsulas de gelatina blanda de 25, 50 Y 100 mg y en suspensión oleosa donde 100mg equivalen a 1 ml.

    Las cápsulas parecen tener mayor biodisponibilidad.

    Fármaco lipofílico pero cuya absorción se afecta poco por los alimentos EXCEPTO por el zumo de pomelo que la modifica.

    Se metaboliza en el hígado y se excreta por la bilis.

    En los niños hay un mayor aclaramiento renal de la sustancia.

    Interacciones medicamentosas

    Atención con los fármacos nefrotóxicos: aminoglucosidos, anfoericina B, Ciprofloxacino, trimetropina.

    Antiinflamatorios no esteroideos (Mínimas dosis).

    Puede potenciar el efecto de la lovastatina, cochicina, toxicidad neuromuscular.

    Atención con los agentes que intervienen con el citocromo P 450.

    Puede aumentar los nivels de Ciclosporina: Ketoconazol, macrólidos (eritromicina, josamicina, doxiciclina).los contraceptivos orales, bloqueantes del canal del calcio (dilitiazem, nicardipino). Puede darse en embarazadas pero no en la lactancia.

    Indicaciones principales

    Psoriasis: dosis 3-5 mg/kg/día; se inicia por 3 mg/kg/día y, si en 3 semanas no se consigue respuesta aceptable se sube a un máximo de 5 mg/ kg; la ciclosporina empieza a ser efectiva en 15 días.

    Se recomienda hacer tandas de tratamiento cortas; 3 meses de máximo con interrupción brusca o paulatina (es indiferente); nunca pasar de 2 años seguidos (máximo de la terapia continua). Es útil en artropatía y en psoriasis ungueal.

    Side Effects

    Afectación renal: lo más preocupante es la fibrosis intersticial si se superan los 2 años de tratamiento y se administran dosis altas.

    Hipertensión arterial: similar.

    Hipertricosis, hiperplasia gingival, acné, seborrea, granulomas piogénicos periungueales.

    Complicaciones neurológicas

    Temblor, disestesias y parestesias, aparecen a los 3 meses y se atenúan, van ligadas al déficit de magnesio y de colesterol. Se asocia a niveles altos de tensión arterial y vasoconstricción periférica.

    Síntomas mayores: convulsiones, alucinaciones, ataxia, afasia.

    Síntomas menores: temblor, insomnio, ansiedad, amnesia, cefalea.

    Contraindicaciones

    Anomalías de la función renal.

    Insuficiencia hepática.

    HTA no controlada.

    Infecciones en curso de evolución; HIV, hepatitis B y C.

    Neoplasias cutáneas antiguas o concurrentes (excepto BCC).

    Déficit inmunitarios.

    NO es teratógena. Por tanto, en caso de necesidad, se puede administrar durante el embarazo.

    Control terapéutico

    Antes del tratamiento:

    Tensión arterial.

    Creatinina, potasio, ácido úrico.

    Colesterol, triglicéridos.

    Magnesio.

    GOT, GPT, Bilirrubina.

    HIV, VHB, VHC.

    Embarazo.

    Durante el tratamiento: Mismo control, primero cada 15 días (primer mes) y después mensual.

    Modificaciones en función del control terapéutico

    En caso de HTA diastólica superior a 95 (mantenida): disminuir dosis o administar nifedipina; si en 15 días se mantiene, parar el tratamiento.

    En caso de aumento de creatinina: si sube un 30% el valor basal, se disminuye la dosis; en caso de que el tratamiento dure un año se solicita la tasa de filtración glomerular.

    En caso de hiperlipemia: dieta y valorar fibratos, nunca inhibidores de la HMG CoA reductasa.

    En caso de hipomagnesemia; potencial riesgo de neuro y nefrotoxicidad; se administra por vía oral.

    Tratamientos biológicos

    Estamos cerca del problema etiopatogénico de la psoriasis, ya que podemos actuar específicamente en el intríngulis del mecanismo inflamatorio, existiendo 3 maneras de actuar:

    • Modulando los agentes que actúan sobre la células T: alfacept y el efalizumab
    • Inhibidores del Factor de necrosis tumoral-alpha: etanercept, infliximab
    • Inhibidores de la interleukina L12 y IL 23: Ustekinumab

    Intrucciones para el paciente con adalimumab, etanercept, ustekinumab e infliximab

    Su dermatólogo le ha recetado un tratamiento específico y selectivo para su psoriasis que controlará las lesiones cutáneas y mejorará mucho su calidad de vida. Uno de los posibles riesgos del mismo es la aparición de infecciones. Es por ello que creemos conveniente que lea con atención las siguientes recomendaciones para su prevención:

    • Informe a su médico de familia de que está realizando este tratamiento
    • Evite, en lo posible, el contacto continuado con personas que padezcan enfermedades infecto-contagiosas
    • No fume
    • Evite la ingerir queso fresco, azul, de roquefort y, en general, productos lácteos no pasteurizados
    • Evite el contacto con excrementos de pájaro (limpieza de jaulas) o con acuarios
    • Acuda de inmediato a su dermatólogo en caso de fiebre, tos, ahogo, dolor de cabeza, dolor de garganta o en otra zona del cuerpo, y también si nota la aparición de úlceras o granos con pus en el cuerpo
    • Extreme la precaución en los viajes a países con riesgo de enfermedades infecciosas: beba agua embotellada, prevenga las picaduras de artrópodo y vacúnese antes de viajar (consultar cuales puede recibir)
    • Evite las vacunas con virus vivos (el resto, como las de la gripe, son seguras)
    • Si va a ser intervenido quirúrgicamente, avise a su dermatólogo
    • En caso de cirugía mayor hay que suspender el tratamiento 2 semanas antes y reinstaurarlo tras el cierre completo de la herida quirúrgica
    • En caso de cirugía menor, se recomienda llevarla a cabo entre infusiones y puede recomendarse amoxicilina 2g 1 hora antes (claritromicina en alérgicos)

    Etanercept (Enbrel)

    Desde 2003 conocemos su seguridad al ser utilizado para la artritis reumatoidea severa y 4 años la seguridad en el psoriasis severo que no responde con los tratamientos clásicos y en especial en el psoriasis artropático. La respuesta aparece ¾ parte de pacientes a los 3 meses. En aquellos que se interrumpió se consigue recapturarlos después de 5 meses.

    Antes del tratamiento se debe de seguir un protocolo para descartar infecciones (tuberculosis, micosis sistémicas, etc.).

    Existen interacciones medicamentosas con vacunas y tratamientos inmunosupresores como la ciclofosfamida. La aparición de neoplasias es similar a la población normal.

    Enbrel

    [Protocolo elaborado por Dr. Sanchez Reñaga, Prof. Pablo Umbert]

    Se trata de una proteína de fusión de Fc de la IgG1 humana y el receptor soluble del TNF. Especialidad de diagnóstico hospitalario y dispensación en farmacia hospitalaria.

    Indicaciones aprobadas

    Psoriasis en placas moderada-grave en adulto

    Psoriasis artropática

    Artritis reumatoidea

    Espondilitis anquilosante

    Hidrosadenitis; atopia.

    Posología en la psoriasis

    50 mg subcutáneo 2 días a la semana, durante 12 semanas.

    Efectivo desde la segunda semana.

    Posteriormente, 25 mg 2 días a la semana, con duración variable.

    Monitorización antes y después del tratamiento

    Antes del tratamiento:

    Siempre PPD, radiografía de tórax.

    Hemograma; GOT-GPT; HIV; VHB; VHC; anamnesis básica (neoplasia subyacente). Descartar embarazo (categoría B); se secreta por la leche materna.

    Después del tratamiento: no requiere ninguna monitorización concreta; sólo hay que controlar la posible aparición de linfomas a largo plazo.

    Side Effects

    Reacciones leves en el punto de inyección.

    Sd.pseudogripal (45%).

    Infecciones (35%) generalmente del tracto respiratorio superior y leves.

    ANA (11%); anticuerpos anti-Enbrel: raros.

    No anafilaxia.

    Inicio o exacerbación de insuficiencia cardiaca o Sd desmielinizantes.

    Interacciones farmacológicas

    No tiene; precaución con vacunas.

    Consideraciones especiales

    Es muy efectivo.

    Se tolera bien y es fácil de manejar.

    Actúa rápidamente.

    Se puede asociar a otros fármacos.

    Puede ser seguro en hepatópatas

    Hay que realizar un seguimiento del paciente por el riesgo de linfomas.

    Ustekinumab (Stelara)

    Sin duda es el tratamiento biológico ideal, por su gran eficacia, seguridad, y comodidad, como refleja la publicación de resultados a largo plazo, con controles superiores a 3 años (Br. Journal of Dermatology, 22 de febrero de 2012).

    El Instituto Nacional de Salud Americano (NICE) ha evaluado sus resultados en ensayos clínicos y ha concluido que tiene mayor probabilidad de respuesta que el etanercept o el adalimumab, pero menor respuesta que el infliximab.

    Su eficacia es de un 75% con dosis semanales de 45 mg-90 mg hasta la cuarta semana y cada 3 meses hasta la semana 40, teniendo en cuenta que se pude continuar el tratamiento o interrumpirlo hasta un nuevo brote.

    El 80% de los 766 pacientes del estudio permanecieron con el tratamiento hasta 3 años. Entre los pacientes que continuaron con el tratamiento, el 82% (90 mg) lo recibían cada 3 meses.

    La comodidad de admininstrar 1 inyección cada 12 semanas es importante para lograr un mayor cumplimiento terapéutico.

    Por todo esto, es un tratamiento muy indicado en aquellos pacientes que no responden a otros biológicos.

    El problema es su alto coste. Por este motivo sólo lo prescribimos en aquellos pacientes que no han respondido con los otros tratamientos, en su mayoría eficaces y fáciles de controlar para evitar efectos secundarios.

    EN EL TRATAMIENTO DE LA PSORIASIS YA NO SOMOS UNOS ESPECTADORES COMO ANTAÑO. TENEMOS EN NUESTRAS MANOS OPCIONES EFICACES QUE HAN MODIFICADO LAS ESPERANZAS DE NUESTROS PACIENTES.

    Doctor Pablo Umbert