PSORIASIS: Causes and treatments
Why is it produced?
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
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
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?
Etiopathogenesis
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
Patients go through outbreaks and stability phases. Outbreaks typically affect the self-esteem of most patients.
My experience with the disease
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
Therapeutic Strategy
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
“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
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
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
Narrow UVB Band
- 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
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
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
- 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
- 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)
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
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)
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.