Psoriasis

PSORIASIS: from greek “psōriasis”, which come from “psōra” (scab) which derive from “psân” (toscratch).

GENERALITY OF PSORIASIS

Psoriasis is an inflammatory T-cell mediated chronic skin disorder. It is mainly due to an alteration of skin maturation, indeed epidermal hyperproliferation cause the activation of the immune system and lead to vascular changes and inflammation.

It has multifactorial origins, and is characterized by elementary lesions such as  erithema, scales, plaques, and papules.

 

EPIDEMIOLOGY OF PSORIASIS

In Caucasian race the percentage of patient affected is between 1,4%-4,8%; while in Asio-Africans populations is very much lower ranging between 0,4%-0,7%. In the United States of America it turns around 2,2%-2,6%. In Italy 3% of the population is affected, while around Australian aborigens and American natives populations there are not affected patients at all, probably due to the conditions in which this peoples live, very much in contact with sun (TABLE 4.1).

TABLE 4.1 Epidemiology of psoriasis percentages according to several  populations.

POPULATION % PSORIASIS
Caucasian race 1,4%-4,8%
Asio-African races 0,4%-0,7%
USA Population 2,2%-2,4%
Italy Population 3%
Germany 1,3%
UK 1,5%
Aborigens and American Native Any

 

PATHOGENESIS OF PSORIASIS

As we said psoriasis is a multifactorial disease, and a polygenic disease, wich means that to show it needs several factors and several genes.

Involved antigens

There are two types of psoriasis, their classification is based on the expression of  hystocompatibility antigens: Type I psoriasis and type II psoriasis.

Type I psoriasis has an high familiar inheritability, and shows in patients with an age below 46 y.o. (y.o. = years old), the pick has been registered between 16 and 22 y.o. patients. It is associated with the following antigens:

  • HLA-B17
  • HLA-B27
  • HLA-Cw6
  • HLA –DR7

Type I psoriasis has a low family inheritability, and shows in patients with an age above 55 y.o. It is associated with the following antigens:

  • HLA-Cw
  • HLA-DR

Triggering factors

Psoriasis is a polygenic disease, which means that it doesn’t follow the mendelian transmission model, but is susceptible to many triggering factors. This factors can be Non-genetic or genetic.

Non-genetic triggering factors

Non genetic triggering factors can be divided into exogen or endogen:

Exogen – Non-genetic triggering factors are:

  • Stress
  • Infections ( such as Streptococcus β-emolithic infections)
  • Drugs (such as β-blockers and lithium)
  • Ultraviolet radiations
  • Smoke
  • Injuries

Endogen – Non-genetic triggering factors are:

  • Obesity
  • Pregnancy
  • Confinement (lying-in or puerperium)

Genetic triggering factors

Nine loci nonetheless have been identified as genetic triggering factors, and the most significant has been found in the class I HLA (Human Leukocyte Antigen) region of chromosome 6p21.3 (HLA-Cw6), which is involved in 30-50% of cases and it has been called PSOR1.

In the short harm of chromosome 6 do exist three loci involved in psoriasis manifestation and are:

  • PSOR1
  • HCR
  • CDSN (corneodesmosin)

Hystopathogenesis of psoriasis

Psoriasis is caused by a keratinocytes hyper-proliferation and differentiation, which is mainly caused by T- lymphocyte. T-cells are involved in the production of proinflammatory cytokines and Grow Factors. Although there are several other cells involved, which lead to the psoriatic manifestations, due to the release of inflammatory cytokines;  and are:

  • Endothelial cells
  • Fibroblasts
  • Keratinocytes
  • Langherans cells
  • Macrophages
  • Polimorphonucleates
  • T-Cells

 T-cells and acquired immunity

An hypothesis is that T- lymphocyte mediate the defense that our body trigger against external antigens such as:

  • Bacteria
  • Virus
  • Self-antigens
  • Superantigens
  • Aminoacids
  • Autologs keratins

According to the previous hypothesis the lymphocyte under the influence of kemokynes migrates toward lymphonodes where it can interact with antigen presenting cells, and so the lymphocyte can differentiate into a mature T-lymphocyte and migrate toward the cutis. Where interacting with keratinocytes and host cells leads to the production of cytokines and chemokines.

Innate immunity role in psoriasis

Innate immunity is characterized by proteins of the Complement, cytokines, it doesn’t need a previous cellular interaction to promote an inflammatory responce.

Cells of the psoriatic cutis are:

  • Neutrophyles (which are present in the perivascular areas)
  • Natural killer cells (which induce the release of cytokines
  • Plasmocitoid dendritic cells (which are able to release INF-α and TNF)
  • CD11c+ dendritic cells ( which produce IL-23 and IL-20).

The cytokines involved in this disease  are:

  • TNF-α
  • IL-1
  • IL-8
  • IL-12
  • IL-17
  • IL-20
  • IL-22
  • IL-23
  • INF

Hystologically there are two main factor which discriminate psoriasis:

  1. Keratinocytes hyperproliferation
  2. The presence of neutrophyles into epidermis and t-lymphocytes in dermis.

In each and every layer of the epidermis can be observed an increment of mitosis. The most important information we must observe to hystologically diagnose psoriasis are:

  • Paracheratosis areas with neutrophyle inside.
  • Stratched interpapillar cristae
  • Keratinocytes with light cytoplasm in the superficial layers of the epidermis
  • Widen capillaries

The normal keratinocytes need 28 days to pass from the stratum basale to the stratum corneum, while in psoriatic lesions they migrate in just 4 days. This lead the cutis’s thickness to increase 4 to 6 times more than a normal skin.

CLINICAL DIAGNOSIS, VARIETY AND OUTCOMES OF PSORIASIS

Arthropathic psoriasis

Arthropathic psoriasis can appear in 5%-45% of psoriatic patients. Almost 85% of patients affected by arthropathic psoriasis shows superficial signs of the disease before to show the more severe articular symptoms.

The Moll and Wright classification divide this variety of psoriasis into five types:

  1. Interphalangeal distal type
  2. Asymmetric oligoarthritis
  3. Poliarthritis
  4. Spondilitis
  5. Mutilans arthritis

Erithrodermic psoriasis

Erithrodermic psoriasis is caused by drug assumption and induce the vulgaris psoriasis to get worse. Drugs which can get worse the psoriasis are:

  • Not steroidal anti-inflammatory (mainly indometacin)
  • β –blockers
  • lithium salts

Psoriasis guttata

Psoriasis guttata is due to streptococcus β-blockers and is mainly observed in patients very young (10-16 y.o.) . Lesions of this variety do not aggregate and  have a diameter of few millimeters till 1,5 cm and are mainly localized at the proximal ends and at the trunk.

Nummular psoriasis

Nummular psoriasis is a variety of psoriasis guttata and is characterized by wider lesions which reach a diameter of 4cm

Spinulosic psoriasis

Spinulosic psoriasis is a variety of psoriasis guttata with lesions localized at the elbow and knees but causes some problem in the differential diagnosis couse can be confused with lichen planus and with hair pitiriasis rubra.

Inverted psoriasis

Inverted psoriasis is mainly localized in areas of the body where folds or crooks are present like inter-gluteus,  groin (inguen), below the udder (breast) , and the armpit (axillary) regions. It is characterized by very shiny scales and even smooth because of their location in regions which are mainly covered with sweat.

Pustule psoriasis

Pustule psoriasis is distinguished into two types localized and generalized. This variety shows the same lesion, but they differ for the amplitude of the hit area.

Localized palm-plantar psoriasis of Barber

Localized palm-plantar psoriasis of Barber shows scales all around and in the middle of feet plants and hand palms. It is not associated with PSOR1, this information suggest to follow a different  therapeutic approach.

Hallopeau acrodermatitis

Hallopeau acrodermatitis is a particular type of localized pustule psoriasis variety which hit fingers.

Generalized pustule psoriasis of Von Zumbush

Generalized pustule psoriasis of Von Zumbush shows the appearance of several pustules which aggregates in great areas, they start as little random pustules, but than converge forming great lesions.

Nail psoriasis

The psoriasis localized in the nail is usual in vulgaris psoriasis, and in arthropatic and erithrodermic psoriasis varieties, but is some cases it can be the unique manifestations. Are indeed present under-nail hyperkeratosis , which can lead to the detachment of the entire nail (onicolysis).

Psoriasis vulgaris

Psoriasis vulgaris also known as plaque psoriasis involve 80%-90% of patients with psoriasis. Usually this variety of psoriasis shows raised inflammed lesions with a silvery layer on the top called plaque. Psoriasis vulgaris can be fatal as the extreme inflammation and exfoliation cause the inability for the body’s ability to regulate temperature and perform barrier functions. A particular clinical aspect of the psoriasis is the Koebner isomorphism which shows the formation of plaque over a scar or a tattoo. To state the clinical severity of the disease. Is used PASI (Psoriasis Area Severity Index) which evaluate the disease giving a score from 0 to 4.

THERAPY OF PSORIASIS

According to the severity of the illness, to lesion’s location and to the anamnesis of the patient there are several therapy which can be  treated topically or systemically with a pharmacological approach or through the use of non-ablative soft surgical instruments  (phototherapy). So we can distinguish three different treatments for psoriasis:

  • TOPIC DRUGS THERAPY
  • SYSTEMIC DRUGS THERAPY
  • PHOTOTHERAPY

TOPIC DRUGS THERAPY

Generally when the psoriasis cover not more than 20% of the body surface area (BSD) physicians decide upon using mainly a topic pharmacological approach, sometimes associated to  phototherapy, or seldom in association with systemic treatments.

The topic drug treatments can be summarized in the folowng:

  • Emollients and moisturizers and keratolytic agents
  • Vitamin D derivatives
  • Retinoids
  • Corticosteroids

Emollients and moisturizers and keratolytic agents

An emollient such as vasellin, has several functions in the treatment of psoriasis, it lubricate and soothes skin which is dry and flaky; produces an occlusive film which can limit water loss (allowing the re-hydration of the stratum corneum promoting a more pliable skin.

Salicylic acid is a kheratolytic agent which help the detachment of psoriatic scales and reduce hyperkeratosis; it is often used together with emollients and moisturizers and favorite drugs absorption. It can cause side effects such as tinnitus salycilism and hyperventilation.

Coal tar is a moisturizer (a derivative of crude coal) has the function to decrease epidermal cell mitosis and stop the formation of scales. It reduces sebum production and perform an anti-inflammatory action on the psoriatic lesions. Coal tar is used particularly for the cure of guttate psoriasis and for psoriatic lesions localized on the scalp, in the shampoo form. It can be used on psoriatic lesions which are small (around 4 cm). It can cause smart and can sensitize the skin, and it release a strong smell and can stain lesions.

Vitamin D derivatives

Vitamin D was isolated first in 1936 from cod liver. It is produced by the skin thanks to UV-light stimulation. Calcipotriol and Tacalcicol  increase cellular differenciation and inhibit cellular proliferation. It is indicated for the treating of psoriatic plaques, because it reduces scale formation. The tolerated weekly cumulative dose is maximum 5mg. it must not be used in case of pustular or erythrodermic psoriasis due to their increased systemic absorption. Side effects caused by the  use of this drugs are irritation, hypercalcemia hypercalcuria, the formation of renal stones (due to calcitriol intoxication). They must not be used during pregnancy nursing nor on children.

CALCIPOTRIOL– DAIVONEX®/Prodotti Formenti

  • THERAPEUTIC INDICATIONS: as cream or ointment (oin.) it is used for the treatment of psoriasis vulgaris. As cutis solution (cut.sol.) it is used for the treatment of scalp psoriasis.
  • SIDE EFFECTS and CONTRAINDICATIONS: excipients hypersensitivity. Calcium metabolism disorders. Psoriasis guttata, erythrodermic esfoliative and pustules, for high risk of hypercalcemia arise. Contraindicate to patient with kidney or epatic insufficiency, in pregnant woman, during nursing phase, and in children.
  • POSOLOGY AND DOSAGE: twice a day.
  • INTERACTIONS: – –
  • PACKAGED & BRANDED NAMES:
DAIVONEX®/Prodotti Formenti

  • Cream 0,005% 30g
  • sol. 0,005% 30gm
  • 0,005% 30g

PSORCUTAN®/Intendis

  • Cream 0,005% 30g
  • sol. 30ml 50 mcg/ml
  • cr. 0,005% 30g
  • THERAPEUTIC INDICATIONS: topic treatment of psoriasis vulgaris, it can be used also on the face and on the scalp.
  • SIDE EFFECTS and CONTRAINDICATIONS: excipients hypersensitivity. Phosphor-Calcium metabolism disorders. Contraindicate in pregnant woman, during nursing phase, and in children.
  • POSOLOGY AND DOSAGE: once a day before bedtime, or as otherwise indicated by the physician. Gently apply just on the lesion surface
  • INTERACTIONS: UV-ray, sun light.
  • PACKAGED & BRANDED NAMES:

MONOHYDRATE TACALCITOL–TICLAPSOR®/NovartisFarma

TICLAPSOR®/Novartis Farma

  • 4mcg/g 20g

VELLUTAN®/Abiogen Pharma

  • 20 g 4 mcg/g
  • Cut. 20ml 4mcg/g

Retinoids

Tazarotene acts on retinoic acid skin receptors: RARβ-γ and is used as topic drug for the treatment of psoriasis.

TAZAROTENE (retinoid) – ZORAC®/Pierre Fabre Italia

  • THERAPEUTIC INDICATIONS: Is used for a topic treatment of psoriasis vulgaris, in the presence of small and averaged severity shich involve till 10% of b.s. (Body Surface).
  • SIDE EFFECTS and CONTRAINDICATIONS: do not apply in on the face and on the face and the scalp. It should not be used during pregnancy even though presumed, particularly in the nursing phase.
  • POSOLOGY AND DOSAGE: apply once a day (the evening) over the psoriatic lesions , painting attention of covering only the injured surfaces of the skin, and do not apply over 10% of b.s. (Body Surface).
  • INTERACTIONS: medicinal and cosmetic prepared with dehydrating and irritant contents.
  • PACKAGED & BRANDED NAMES:
ZORAC®/Pierre Fabre Italia

  • Gel in water solution 0,05% 15g
  • Gel in water solution 0,1% 15g

Corticosteroids

Topic corticosteroids have an anti-inflammatory result, they decrease vascular permeability, consequently decreasing skin edema and leukocytes penetration into skin. They also have anti-proliferative and immunosuppressive effects. In brief corticosteroids persuit the following functions:

  • Anti-inflammatory
  • Anti-proliferative
  • Immunosuppressive

Corticosteroids can be found in ointment formulations (which help the hydration of the skin, which have good results on dry hyperkeratotic and scaly psoriatic lesions; it can be found as cream which can be used particularly on infected areas; and it can be found as solutions, particularly for scalp psoriasis, but it must be remembered that alcohol based solutions should not be applied over open lesions because they cause pain.  In brief corticosteroid can be found in the following formulations:

  • Ointments
  • Creams
  • Solutions
TELEANGECTASIS: from greek words “telos-“ (end) + “-agheion-“ (vaso) + “-ektasis-“ (estenction). It is an alteration of the cutis and sometime of the oral mucosa, with the appearing of dilated superficial blood vessels.

ECCHYMOSIS: from greek “ek-“ (outside) + “–chymos- “ (juice) + “–osis” (condition). It is synonym of bruise; it is a subcutaneous extravasation of blood larger than 1 .

PYOGENIC: it comes from greek “pyon” (pus) + “genes” (which generate). pyogenic agents are able to produce an inflammatory reaction followed by pus production. Such substances  or microorganisms have a positive kemiotattic action which means that they attract leukocytes (white blood cells).

Corticosteroids can produce side effects. Can cause a systemic absorption, can cause Dermal atrophy, telangiectasis  or angioectasias (also known as spider veins) which are small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Corticosteroids can cause also ecchymosis. They can also cause peri-orbital acne and poor wound healing, and can favorite the formation of pyogenic infections. In breaf corticosteroids can cause the following side effects:

  • Systemic absorption
  • Dermal atrophy
  • Telangiectasis
  • Ecchimosis
  • Periorbital acne
  • Poor wound healing
  • Pyogenic infections

 

 

 

TABLE 4.2 Classification of corticosteroids.

POTENCY CORTICOSTEROID BRANDED NAMES
 

Ultra-High

 

 

Halobetasol propinate ULTRAVATE®
 

Colbetasol propinate

TEMOVATE®

CLOBESOL®

OLUX®

Betamethasone dipropionate DIPROLENE®
Diflorasone diacetate PSORCON®
 

 

 

High

 

Halcinonide HALOG®
Amicinonide CYLOCORT®
Betamethasone dipropinate DIPROLENE-AF®
Mometasone furoate ELOCON®
Diflorasone diacetate FLORONE®
Fluocinonide LIDEX®
Desoximetasone TOPICORT®
 

Mild to High

 

Halcinonide HALOG®
Triamicinoone  acetonide ARISTOCORT®
Betamethasone dipropionate DIPROSONE®
Fluocinonide LIDEX-E®
 

 

Mild

 

Hydrocortisone valerate WESTCORT®
Triamicinolone acetonide KENALOG®
Flurandrenolide CORDRAN®
Mometasone furoate ELOCON®
Fluocinolone acetonide SYNALAR®
 

 

 

Low to Mild

 

 

Hydrocortisone valerate WESTCORT®
Triamicinolone acetonide KENALOG®
Flurandrenolide CORDRAN®
Betamethasone dipropionate DIPROSONE®
Hydrocortisone bytyrate LOCOID®
Flucolone acetonide SYNALAR®
 

 

Low

 

Alclometasne dipropionate ACLOVATE®
Betamethasone valerate VALISONE®
Hydrocortisone, Dexamethasone, Prednisolone, Methylprednisolone SYNALAR®

SYSTEMIC DRUG THERAPY

When the psoriasis cover more than 20% of the body surface area (BSD) physicians decide upon using mainly a systhemic pharmacological approach , sometimes associated to  phototherapy, and in association with topic treatments.

The election drugs for a systemic treatment of psoriasis are:

  • Acitretin
  • Ciclosporin (Cs)
  • Methotrexate
  • Fumaric acid derivatives
  • Biological molecules

Acitretin

Acitretin is a retinoid of second generation; it is an active metabolite of etretinate (etretinate withdraw in United States in 1998). Because of its side effects it is restricted to treatment of really severe psoriasis cases.

ACITRETIN (retinoid) – SORIATANE®

  • THERAPEUTIC INDICATIONS: Psoriasis, ittiosiforme state, palmar cheratoderma, Darier illness and lichen planus.
  • SIDE EFFECTS and CONTRAINDICATIONS: this drug is highly teratogen and must not be taken during pregnancy and nor nursing, and in woman who do not use contraceptives. Epatic and renal insufficiency. Must not be used I nassociation with tetraciclin metotrexato, vitamine A, or any other retinoids. patients which shows constant high level of sieric lipid.
  • POSOLOGY AND DOSAGE:
  • INTERACTIONS: Retinoids. Fenitioina. Progestinic. Metotrexato. Tetraiclins. Ethylic alcohol.
  • PACKAGED & BRANDED NAMES:
NEOTIGASON®/Roche

  • 20cps 35mg
  • 30cps 10mg

SORIATANE®

Methotrexate

Methotrexate is used for severe psoriasis which doesn’t respond correctly to topical treatments. It can suppress B-cells and macrophages, and induce T-cells to apoptosis, it suppresses IL-1 and IL-8 priduction by peripheral blood mononuclear cells and reduces T-cell production of INF-γ and of TNF.

METHOTREXATE – METHOTREXATE®

  • THERAPEUTIC INDICATIONS: acute leukemia rheumatoid arthritis, arthropathic psoriasis, psoriasis, mammary carcinoma, coriocarcinoma and similar trophoblastic affections, micosis fungoides, lymphatic leukemia and meningitis.
  • SIDE EFFECTS and CONTRAINDICATIONS: CONTROINDICATIONS this drug must not be taken during pregnancy and nor nursing. Do not use in patients with renal or liver problems, or with preexisting anemia, leukopeina thrombocytopenia, in alcoholics, and in patients with active infectious disease. SIDE EFFECTS It can cause headache, chills, fever, fatigue, abdominal pain, nausea, vomiting, dizziness. Pruritis, alopecia, urticaria, ecchimosis, sunborn (phototoxicity). Osteopathy. Pulmonary fibrosis.
  • POSOLOGY AND DOSAGE: 2,5-5mg 12h x 3dose week. For injections 50-75mg/week, in association with folic acid.
  • INTERACTIONS: salicilates, sulphonamides, (diuretics, antibacterial, hypoglycemic) tetracyclin, clorafenico, epatotoxic drugs: retinoids leflunomide, azatioprin sulfasalazin.
  • PACKAGED & BRANDED NAMES:
METHOTREXATE®/Wyeth Lederle

  • 25 cpr. 2,5mm
  • 1fl. 1g/10ml

METOTRESSATO TEVA®/Teva Pharma Italia

METOTREXATO  MAYNE®/Mayne Pharma (Italia)

Cyclosporine (Cs)

Is used for moderate and severe forms of psoriasis which resists to other therapies. Cyclosporine is an immunosuppressant widely used in organs transplantation. This therapy can last even several months.

CYCLOSPORINE – SANDIMMUN®/Novartis Farma

  • THERAPEUTIC INDICATIONS: Bone marrow transplantations, endogen uveite, nefrosic syndrome, severe psoriasis, rheumatoid arthritis, atopic dermatitis.
  • SIDE EFFECTS and CONTRAINDICATIONS: CONTRAINDICATIONS Hypersensibility to the active molecule, preparation with Hypericum perforatum. SIDE EFFECTS headaches, paresthesias, flu-like symptoms, abdominal pain, nausea. Hypertension, Nephrotoxicity, neurotoxicity, hepatotoxicity, hyperglycemia. Do not use over one year to avoid further side effects.
  • POSOLOGY AND DOSAGE: initially 2,5mg/kg/day ; than may increase the dose at 2week intervals of 0,5 mg/kg/day; do not override the dose of 5mg/kg/day.
  • INTERACTIONS: antibiotics, or substances nephrotoxic (aminoglicosides, amfotericin B, ciprofloxacin, colchicin and trimethoprim), FANS particularly clofenac, lovastatin, inhibitors of the epathic system of cytochrome P450. Ketoconazol, eritromicin, doxiciclin, propafenon, calcium antagonists, barbiturici, carbamazepin, fenitoin, metamizol, rifampicin, nafcillin, sulfadimidin, trimetoprim, hypericum perforatum, metilprednisolon, prednisolon, josamicin.
  • PACKAGED & BRANDED NAMES:
SANDIMMUN®/Novartis Farma

  • 30 cps. 100mg
  • 25mg
  • 50mg

Fumaric acid derivatives

Fumaric acid derivatives are not yet used in Italy but they give seveare gastrointestinal side effects.

Biological molecules

Biological molecules are monoclonal antibody, of fusion proteins, which can inhibit the triggering factors of psoriasis. This molecules can be distinguished into two groups:

Molecules which target is TNF-α (infliximab, etanercept, adlimumab)

Molecules which selectively block the activation and the division of T-cells (efalizumab). This drugs are available and used for treatment of psoriasis vulgaris, and arthropathic.

Patients treated with anti-TNF-α have  an high risk to get tubercholosis, because of the induced apoptosis.

 

PHOTOTERAPY

Phototherapy has been used for over 100 years to moisten severe psoriasis, the 313 nanometers  wavelength is the most effective for psoriasis treatment. The ultraviolet arrays of 315-400 nanometers and Ultraviolet B (290-320 nm) are an efficient therapy.

Ultraviolet B

Ultraviolet B is not toxic, and can be used as a single agent. Is usually combined with lubricants.  Ultraviolet B lamps TL01 (311-313nm)  are particularly efficient in psoriasis which resist to topic treatments.

P+UVA therapy (Psolaren + UVA)

PUVA therapy is used for :

  • Psoriasis guttata
  • Psoriasis vulgaris
  • Inverted psoriasis

The patients take orally psoralen (8-methoxypsoralen, 5-mehoxypsoralen and trioxalen,) which have a photosensitive action, and after two hours the patient is irradiated with ultraviolet arrays. Psoralen intercalate into DNA , inhibiting DNA replication and thus, inhibiting epidermal cell hyperproliferation. The free radicals formation cause a damage to cell membranes, as well as in cytoplasmic contents and to the nucleus of epidermal cells, so inhibiting cell growth. PUVA therapy is administered 2-4 times a week for 4-8 weeks (almost 20 sessions). SIDE EFFECTS of PUVA therapy can be: constipation diarrhea, nausea, vomiting, itching, erithema. And a prolongued use of psoralen can lead to cataracts, and skin cancer.

PUVA therapy increases the apoptosis of activated T-Cells.

New therapies

The monoclonal antibody anti-IL-12/13 and adalimumab (which binds specifically to TNF-α and blocks its interaction with the p55 and p75 cell surface TNF receptors) is not yet been approved but is on pre marketing study.


 

TABLE 3.2 Therapy of psoriasis related to the severity.

THERAPY DRUGS
 

 

 

 

Topic > 20% BSD

 

 

 

EMOLLIENTS

VASELINE

VITAMIN D DERIVATIVES

CALCIPOTRIOL

TACALCITOL

RETINOID

TAZAROTEN

CORTICOSTEROIDS

 

 

 

 

 

 

 

 

Systemic < 20% BSD

 

 

RETINOIDS

ACITRETIN

METHOTREXATE

CICLOSPORIN

FUMARIC ACID DERIVATIVES

BIOLOGICAL MOLECULES

1st group: (TNF-α target)

INFLIXIMAB

ETANERCEPT

ADALIMUMAB

2nd group: (T-limphocytes blockers)

EFALIZUMAB

 

 

Phototherapy

 

 

ISOTRETIONIN

TRIAMCINOLONE ACETONIDE

 

TABLE 3.2 Therapy costs

THERAPY TWELVEMONTHLY COSTS
STEROIDS 500,00€/2.000,00€
DOVONEX 2.000,00€/8.000,00€
UVB 2.000,00€
PUVA 3.500,00€
SORIATANE 6.500,00€
METHOTREXATE 1.500,00€/2.500,00€
CYCLOSPORINE 5.000,00€
BIOLOGICAL MOLECULES 10.000,00€/15.000,00€

 

 

PSORIASIS: from greek “psōriasis”, which come from “psōra” (scab) which derive from “psân” (toscratch).

GENERALITY OF PSORIASIS

Psoriasis is an inflammatory T-cell mediated chronic skin disorder. It is mainly due to an alteration of skin maturation, indeed epidermal hyperproliferation cause the activation of the immune system and lead to vascular changes and inflammation.

It has multifactorial origins, and is characterized by elementary lesions such as  erithema, scales, plaques, and papules.

 

EPIDEMIOLOGY OF PSORIASIS

In Caucasian race the percentage of patient affected is between 1,4%-4,8%; while in Asio-Africans populations is very much lower ranging between 0,4%-0,7%. In the United States of America it turns around 2,2%-2,6%. In Italy 3% of the population is affected, while around Australian aborigens and American natives populations there are not affected patients at all, probably due to the conditions in which this peoples live, very much in contact with sun (TABLE 4.1).

TABLE 4.1 Epidemiology of psoriasis percentages according to several  populations.

POPULATION % PSORIASIS
Caucasian race 1,4%-4,8%
Asio-African races 0,4%-0,7%
USA Population 2,2%-2,4%
Italy Population 3%
Germany 1,3%
UK 1,5%
Aborigens and American Native Any

 

PATHOGENESIS OF PSORIASIS

As we said psoriasis is a multifactorial disease, and a polygenic disease, wich means that to show it needs several factors and several genes.

Involved antigens

There are two types of psoriasis, their classification is based on the expression of  hystocompatibility antigens: Type I psoriasis and type II psoriasis.

Type I psoriasis has an high familiar inheritability, and shows in patients with an age below 46 y.o. (y.o. = years old), the pick has been registered between 16 and 22 y.o. patients. It is associated with the following antigens:

  • HLA-B17
  • HLA-B27
  • HLA-Cw6
  • HLA –DR7

Type I psoriasis has a low family inheritability, and shows in patients with an age above 55 y.o. It is associated with the following antigens:

  • HLA-Cw
  • HLA-DR

Triggering factors

Psoriasis is a polygenic disease, which means that it doesn’t follow the mendelian transmission model, but is susceptible to many triggering factors. This factors can be Non-genetic or genetic.

Non-genetic triggering factors

Non genetic triggering factors can be divided into exogen or endogen:

Exogen – Non-genetic triggering factors are:

  • Stress
  • Infections ( such as Streptococcus β-emolithic infections)
  • Drugs (such as β-blockers and lithium)
  • Ultraviolet radiations
  • Smoke
  • Injuries

Endogen – Non-genetic triggering factors are:

  • Obesity
  • Pregnancy
  • Confinement (lying-in or puerperium)

Genetic triggering factors

Nine loci nonetheless have been identified as genetic triggering factors, and the most significant has been found in the class I HLA (Human Leukocyte Antigen) region of chromosome 6p21.3 (HLA-Cw6), which is involved in 30-50% of cases and it has been called PSOR1.

In the short harm of chromosome 6 do exist three loci involved in psoriasis manifestation and are:

  • PSOR1
  • HCR
  • CDSN (corneodesmosin)

Hystopathogenesis of psoriasis

Psoriasis is caused by a keratinocytes hyper-proliferation and differentiation, which is mainly caused by T- lymphocyte. T-cells are involved in the production of proinflammatory cytokines and Grow Factors. Although there are several other cells involved, which lead to the psoriatic manifestations, due to the release of inflammatory cytokines;  and are:

  • Endothelial cells
  • Fibroblasts
  • Keratinocytes
  • Langherans cells
  • Macrophages
  • Polimorphonucleates
  • T-Cells

 T-cells and acquired immunity

An hypothesis is that T- lymphocyte mediate the defense that our body trigger against external antigens such as:

  • Bacteria
  • Virus
  • Self-antigens
  • Superantigens
  • Aminoacids
  • Autologs keratins

According to the previous hypothesis the lymphocyte under the influence of kemokynes migrates toward lymphonodes where it can interact with antigen presenting cells, and so the lymphocyte can differentiate into a mature T-lymphocyte and migrate toward the cutis. Where interacting with keratinocytes and host cells leads to the production of cytokines and chemokines.

Innate immunity role in psoriasis

Innate immunity is characterized by proteins of the Complement, cytokines, it doesn’t need a previous cellular interaction to promote an inflammatory responce.

Cells of the psoriatic cutis are:

  • Neutrophyles (which are present in the perivascular areas)
  • Natural killer cells (which induce the release of cytokines
  • Plasmocitoid dendritic cells (which are able to release INF-α and TNF)
  • CD11c+ dendritic cells ( which produce IL-23 and IL-20).

The cytokines involved in this disease  are:

  • TNF-α
  • IL-1
  • IL-8
  • IL-12
  • IL-17
  • IL-20
  • IL-22
  • IL-23
  • INF

Hystologically there are two main factor which discriminate psoriasis:

  1. Keratinocytes hyperproliferation
  2. The presence of neutrophyles into epidermis and t-lymphocytes in dermis.

In each and every layer of the epidermis can be observed an increment of mitosis. The most important information we must observe to hystologically diagnose psoriasis are:

  • Paracheratosis areas with neutrophyle inside.
  • Stratched interpapillar cristae
  • Keratinocytes with light cytoplasm in the superficial layers of the epidermis
  • Widen capillaries

The normal keratinocytes need 28 days to pass from the stratum basale to the stratum corneum, while in psoriatic lesions they migrate in just 4 days. This lead the cutis’s thickness to increase 4 to 6 times more than a normal skin.

CLINICAL DIAGNOSIS, VARIETY AND OUTCOMES OF PSORIASIS

Arthropathic psoriasis

Arthropathic psoriasis can appear in 5%-45% of psoriatic patients. Almost 85% of patients affected by arthropathic psoriasis shows superficial signs of the disease before to show the more severe articular symptoms.

The Moll and Wright classification divide this variety of psoriasis into five types:

  1. Interphalangeal distal type
  2. Asymmetric oligoarthritis
  3. Poliarthritis
  4. Spondilitis
  5. Mutilans arthritis

Erithrodermic psoriasis

Erithrodermic psoriasis is caused by drug assumption and induce the vulgaris psoriasis to get worse. Drugs which can get worse the psoriasis are:

  • Not steroidal anti-inflammatory (mainly indometacin)
  • β –blockers
  • lithium salts

Psoriasis guttata

Psoriasis guttata is due to streptococcus β-blockers and is mainly observed in patients very young (10-16 y.o.) . Lesions of this variety do not aggregate and  have a diameter of few millimeters till 1,5 cm and are mainly localized at the proximal ends and at the trunk.

Nummular psoriasis

Nummular psoriasis is a variety of psoriasis guttata and is characterized by wider lesions which reach a diameter of 4cm

Spinulosic psoriasis

Spinulosic psoriasis is a variety of psoriasis guttata with lesions localized at the elbow and knees but causes some problem in the differential diagnosis couse can be confused with lichen planus and with hair pitiriasis rubra.

Inverted psoriasis

Inverted psoriasis is mainly localized in areas of the body where folds or crooks are present like inter-gluteus,  groin (inguen), below the udder (breast) , and the armpit (axillary) regions. It is characterized by very shiny scales and even smooth because of their location in regions which are mainly covered with sweat.

Pustule psoriasis

Pustule psoriasis is distinguished into two types localized and generalized. This variety shows the same lesion, but they differ for the amplitude of the hit area.

Localized palm-plantar psoriasis of Barber

Localized palm-plantar psoriasis of Barber shows scales all around and in the middle of feet plants and hand palms. It is not associated with PSOR1, this information suggest to follow a different  therapeutic approach.

Hallopeau acrodermatitis

Hallopeau acrodermatitis is a particular type of localized pustule psoriasis variety which hit fingers.

Generalized pustule psoriasis of Von Zumbush

Generalized pustule psoriasis of Von Zumbush shows the appearance of several pustules which aggregates in great areas, they start as little random pustules, but than converge forming great lesions.

Nail psoriasis

The psoriasis localized in the nail is usual in vulgaris psoriasis, and in arthropatic and erithrodermic psoriasis varieties, but is some cases it can be the unique manifestations. Are indeed present under-nail hyperkeratosis , which can lead to the detachment of the entire nail (onicolysis).

Psoriasis vulgaris

Psoriasis vulgaris also known as plaque psoriasis involve 80%-90% of patients with psoriasis. Usually this variety of psoriasis shows raised inflammed lesions with a silvery layer on the top called plaque. Psoriasis vulgaris can be fatal as the extreme inflammation and exfoliation cause the inability for the body’s ability to regulate temperature and perform barrier functions. A particular clinical aspect of the psoriasis is the Koebner isomorphism which shows the formation of plaque over a scar or a tattoo. To state the clinical severity of the disease. Is used PASI (Psoriasis Area Severity Index) which evaluate the disease giving a score from 0 to 4.

THERAPY OF PSORIASIS

According to the severity of the illness, to lesion’s location and to the anamnesis of the patient there are several therapy which can be  treated topically or systemically with a pharmacological approach or through the use of non-ablative soft surgical instruments  (phototherapy). So we can distinguish three different treatments for psoriasis:

  • TOPIC DRUGS THERAPY
  • SYSTEMIC DRUGS THERAPY
  • PHOTOTHERAPY

TOPIC DRUGS THERAPY

Generally when the psoriasis cover not more than 20% of the body surface area (BSD) physicians decide upon using mainly a topic pharmacological approach, sometimes associated to  phototherapy, or seldom in association with systemic treatments.

The topic drug treatments can be summarized in the folowng:

  • Emollients and moisturizers and keratolytic agents
  • Vitamin D derivatives
  • Retinoids
  • Corticosteroids

Emollients and moisturizers and keratolytic agents

An emollient such as vasellin, has several functions in the treatment of psoriasis, it lubricate and soothes skin which is dry and flaky; produces an occlusive film which can limit water loss (allowing the re-hydration of the stratum corneum promoting a more pliable skin.

Salicylic acid is a kheratolytic agent which help the detachment of psoriatic scales and reduce hyperkeratosis; it is often used together with emollients and moisturizers and favorite drugs absorption. It can cause side effects such as tinnitus salycilism and hyperventilation.

Coal tar is a moisturizer (a derivative of crude coal) has the function to decrease epidermal cell mitosis and stop the formation of scales. It reduces sebum production and perform an anti-inflammatory action on the psoriatic lesions. Coal tar is used particularly for the cure of guttate psoriasis and for psoriatic lesions localized on the scalp, in the shampoo form. It can be used on psoriatic lesions which are small (around 4 cm). It can cause smart and can sensitize the skin, and it release a strong smell and can stain lesions.

Vitamin D derivatives

Vitamin D was isolated first in 1936 from cod liver. It is produced by the skin thanks to UV-light stimulation. Calcipotriol and Tacalcicol  increase cellular differenciation and inhibit cellular proliferation. It is indicated for the treating of psoriatic plaques, because it reduces scale formation. The tolerated weekly cumulative dose is maximum 5mg. it must not be used in case of pustular or erythrodermic psoriasis due to their increased systemic absorption. Side effects caused by the  use of this drugs are irritation, hypercalcemia hypercalcuria, the formation of renal stones (due to calcitriol intoxication). They must not be used during pregnancy nursing nor on children.

CALCIPOTRIOL– DAIVONEX®/Prodotti Formenti

  • THERAPEUTIC INDICATIONS: as cream or ointment (oin.) it is used for the treatment of psoriasis vulgaris. As cutis solution (cut.sol.) it is used for the treatment of scalp psoriasis.
  • SIDE EFFECTS and CONTRAINDICATIONS: excipients hypersensitivity. Calcium metabolism disorders. Psoriasis guttata, erythrodermic esfoliative and pustules, for high risk of hypercalcemia arise. Contraindicate to patient with kidney or epatic insufficiency, in pregnant woman, during nursing phase, and in children.
  • POSOLOGY AND DOSAGE: twice a day.
  • INTERACTIONS: – –
  • PACKAGED & BRANDED NAMES:
DAIVONEX®/Prodotti Formenti

  • Cream 0,005% 30g
  • sol. 0,005% 30gm
  • 0,005% 30g

PSORCUTAN®/Intendis

  • Cream 0,005% 30g
  • sol. 30ml 50 mcg/ml
  • cr. 0,005% 30g
  • THERAPEUTIC INDICATIONS: topic treatment of psoriasis vulgaris, it can be used also on the face and on the scalp.
  • SIDE EFFECTS and CONTRAINDICATIONS: excipients hypersensitivity. Phosphor-Calcium metabolism disorders. Contraindicate in pregnant woman, during nursing phase, and in children.
  • POSOLOGY AND DOSAGE: once a day before bedtime, or as otherwise indicated by the physician. Gently apply just on the lesion surface
  • INTERACTIONS: UV-ray, sun light.
  • PACKAGED & BRANDED NAMES:

MONOHYDRATE TACALCITOL–TICLAPSOR®/NovartisFarma

TICLAPSOR®/Novartis Farma

  • 4mcg/g 20g

VELLUTAN®/Abiogen Pharma

  • 20 g 4 mcg/g
  • Cut. 20ml 4mcg/g

Retinoids

Tazarotene acts on retinoic acid skin receptors: RARβ-γ and is used as topic drug for the treatment of psoriasis.

TAZAROTENE (retinoid) – ZORAC®/Pierre Fabre Italia

  • THERAPEUTIC INDICATIONS: Is used for a topic treatment of psoriasis vulgaris, in the presence of small and averaged severity shich involve till 10% of b.s. (Body Surface).
  • SIDE EFFECTS and CONTRAINDICATIONS: do not apply in on the face and on the face and the scalp. It should not be used during pregnancy even though presumed, particularly in the nursing phase.
  • POSOLOGY AND DOSAGE: apply once a day (the evening) over the psoriatic lesions , painting attention of covering only the injured surfaces of the skin, and do not apply over 10% of b.s. (Body Surface).
  • INTERACTIONS: medicinal and cosmetic prepared with dehydrating and irritant contents.
  • PACKAGED & BRANDED NAMES:
ZORAC®/Pierre Fabre Italia

  • Gel in water solution 0,05% 15g
  • Gel in water solution 0,1% 15g

Corticosteroids

Topic corticosteroids have an anti-inflammatory result, they decrease vascular permeability, consequently decreasing skin edema and leukocytes penetration into skin. They also have anti-proliferative and immunosuppressive effects. In brief corticosteroids persuit the following functions:

  • Anti-inflammatory
  • Anti-proliferative
  • Immunosuppressive

Corticosteroids can be found in ointment formulations (which help the hydration of the skin, which have good results on dry hyperkeratotic and scaly psoriatic lesions; it can be found as cream which can be used particularly on infected areas; and it can be found as solutions, particularly for scalp psoriasis, but it must be remembered that alcohol based solutions should not be applied over open lesions because they cause pain.  In brief corticosteroid can be found in the following formulations:

  • Ointments
  • Creams
  • Solutions
TELEANGECTASIS: from greek words “telos-“ (end) + “-agheion-“ (vaso) + “-ektasis-“ (estenction). It is an alteration of the cutis and sometime of the oral mucosa, with the appearing of dilated superficial blood vessels.

ECCHYMOSIS: from greek “ek-“ (outside) + “–chymos- “ (juice) + “–osis” (condition). It is synonym of bruise; it is a subcutaneous extravasation of blood larger than 1 .

PYOGENIC: it comes from greek “pyon” (pus) + “genes” (which generate). pyogenic agents are able to produce an inflammatory reaction followed by pus production. Such substances  or microorganisms have a positive kemiotattic action which means that they attract leukocytes (white blood cells).

Corticosteroids can produce side effects. Can cause a systemic absorption, can cause Dermal atrophy, telangiectasis  or angioectasias (also known as spider veins) which are small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Corticosteroids can cause also ecchymosis. They can also cause peri-orbital acne and poor wound healing, and can favorite the formation of pyogenic infections. In breaf corticosteroids can cause the following side effects:

  • Systemic absorption
  • Dermal atrophy
  • Telangiectasis
  • Ecchimosis
  • Periorbital acne
  • Poor wound healing
  • Pyogenic infections

 

 

 

TABLE 4.2 Classification of corticosteroids.

POTENCY CORTICOSTEROID BRANDED NAMES
 

Ultra-High

 

 

Halobetasol propinate ULTRAVATE®
 

Colbetasol propinate

TEMOVATE®

CLOBESOL®

OLUX®

Betamethasone dipropionate DIPROLENE®
Diflorasone diacetate PSORCON®
 

 

 

High

 

Halcinonide HALOG®
Amicinonide CYLOCORT®
Betamethasone dipropinate DIPROLENE-AF®
Mometasone furoate ELOCON®
Diflorasone diacetate FLORONE®
Fluocinonide LIDEX®
Desoximetasone TOPICORT®
 

Mild to High

 

Halcinonide HALOG®
Triamicinoone  acetonide ARISTOCORT®
Betamethasone dipropionate DIPROSONE®
Fluocinonide LIDEX-E®
 

 

Mild

 

Hydrocortisone valerate WESTCORT®
Triamicinolone acetonide KENALOG®
Flurandrenolide CORDRAN®
Mometasone furoate ELOCON®
Fluocinolone acetonide SYNALAR®
 

 

 

Low to Mild

 

 

Hydrocortisone valerate WESTCORT®
Triamicinolone acetonide KENALOG®
Flurandrenolide CORDRAN®
Betamethasone dipropionate DIPROSONE®
Hydrocortisone bytyrate LOCOID®
Flucolone acetonide SYNALAR®
 

 

Low

 

Alclometasne dipropionate ACLOVATE®
Betamethasone valerate VALISONE®
Hydrocortisone, Dexamethasone, Prednisolone, Methylprednisolone SYNALAR®

SYSTEMIC DRUG THERAPY

When the psoriasis cover more than 20% of the body surface area (BSD) physicians decide upon using mainly a systhemic pharmacological approach , sometimes associated to  phototherapy, and in association with topic treatments.

The election drugs for a systemic treatment of psoriasis are:

  • Acitretin
  • Ciclosporin (Cs)
  • Methotrexate
  • Fumaric acid derivatives
  • Biological molecules

Acitretin

Acitretin is a retinoid of second generation; it is an active metabolite of etretinate (etretinate withdraw in United States in 1998). Because of its side effects it is restricted to treatment of really severe psoriasis cases.

ACITRETIN (retinoid) – SORIATANE®

  • THERAPEUTIC INDICATIONS: Psoriasis, ittiosiforme state, palmar cheratoderma, Darier illness and lichen planus.
  • SIDE EFFECTS and CONTRAINDICATIONS: this drug is highly teratogen and must not be taken during pregnancy and nor nursing, and in woman who do not use contraceptives. Epatic and renal insufficiency. Must not be used I nassociation with tetraciclin metotrexato, vitamine A, or any other retinoids. patients which shows constant high level of sieric lipid.
  • POSOLOGY AND DOSAGE:
  • INTERACTIONS: Retinoids. Fenitioina. Progestinic. Metotrexato. Tetraiclins. Ethylic alcohol.
  • PACKAGED & BRANDED NAMES:
NEOTIGASON®/Roche

  • 20cps 35mg
  • 30cps 10mg

SORIATANE®

Methotrexate

Methotrexate is used for severe psoriasis which doesn’t respond correctly to topical treatments. It can suppress B-cells and macrophages, and induce T-cells to apoptosis, it suppresses IL-1 and IL-8 priduction by peripheral blood mononuclear cells and reduces T-cell production of INF-γ and of TNF.

METHOTREXATE – METHOTREXATE®

  • THERAPEUTIC INDICATIONS: acute leukemia rheumatoid arthritis, arthropathic psoriasis, psoriasis, mammary carcinoma, coriocarcinoma and similar trophoblastic affections, micosis fungoides, lymphatic leukemia and meningitis.
  • SIDE EFFECTS and CONTRAINDICATIONS: CONTROINDICATIONS this drug must not be taken during pregnancy and nor nursing. Do not use in patients with renal or liver problems, or with preexisting anemia, leukopeina thrombocytopenia, in alcoholics, and in patients with active infectious disease. SIDE EFFECTS It can cause headache, chills, fever, fatigue, abdominal pain, nausea, vomiting, dizziness. Pruritis, alopecia, urticaria, ecchimosis, sunborn (phototoxicity). Osteopathy. Pulmonary fibrosis.
  • POSOLOGY AND DOSAGE: 2,5-5mg 12h x 3dose week. For injections 50-75mg/week, in association with folic acid.
  • INTERACTIONS: salicilates, sulphonamides, (diuretics, antibacterial, hypoglycemic) tetracyclin, clorafenico, epatotoxic drugs: retinoids leflunomide, azatioprin sulfasalazin.
  • PACKAGED & BRANDED NAMES:
METHOTREXATE®/Wyeth Lederle

  • 25 cpr. 2,5mm
  • 1fl. 1g/10ml

METOTRESSATO TEVA®/Teva Pharma Italia

METOTREXATO  MAYNE®/Mayne Pharma (Italia)

Cyclosporine (Cs)

Is used for moderate and severe forms of psoriasis which resists to other therapies. Cyclosporine is an immunosuppressant widely used in organs transplantation. This therapy can last even several months.

CYCLOSPORINE – SANDIMMUN®/Novartis Farma

  • THERAPEUTIC INDICATIONS: Bone marrow transplantations, endogen uveite, nefrosic syndrome, severe psoriasis, rheumatoid arthritis, atopic dermatitis.
  • SIDE EFFECTS and CONTRAINDICATIONS: CONTRAINDICATIONS Hypersensibility to the active molecule, preparation with Hypericum perforatum. SIDE EFFECTS headaches, paresthesias, flu-like symptoms, abdominal pain, nausea. Hypertension, Nephrotoxicity, neurotoxicity, hepatotoxicity, hyperglycemia. Do not use over one year to avoid further side effects.
  • POSOLOGY AND DOSAGE: initially 2,5mg/kg/day ; than may increase the dose at 2week intervals of 0,5 mg/kg/day; do not override the dose of 5mg/kg/day.
  • INTERACTIONS: antibiotics, or substances nephrotoxic (aminoglicosides, amfotericin B, ciprofloxacin, colchicin and trimethoprim), FANS particularly clofenac, lovastatin, inhibitors of the epathic system of cytochrome P450. Ketoconazol, eritromicin, doxiciclin, propafenon, calcium antagonists, barbiturici, carbamazepin, fenitoin, metamizol, rifampicin, nafcillin, sulfadimidin, trimetoprim, hypericum perforatum, metilprednisolon, prednisolon, josamicin.
  • PACKAGED & BRANDED NAMES:
SANDIMMUN®/Novartis Farma

  • 30 cps. 100mg
  • 25mg
  • 50mg

Fumaric acid derivatives

Fumaric acid derivatives are not yet used in Italy but they give seveare gastrointestinal side effects.

Biological molecules

Biological molecules are monoclonal antibody, of fusion proteins, which can inhibit the triggering factors of psoriasis. This molecules can be distinguished into two groups:

Molecules which target is TNF-α (infliximab, etanercept, adlimumab)

Molecules which selectively block the activation and the division of T-cells (efalizumab). This drugs are available and used for treatment of psoriasis vulgaris, and arthropathic.

Patients treated with anti-TNF-α have  an high risk to get tubercholosis, because of the induced apoptosis.

 

PHOTOTERAPY

Phototherapy has been used for over 100 years to moisten severe psoriasis, the 313 nanometers  wavelength is the most effective for psoriasis treatment. The ultraviolet arrays of 315-400 nanometers and Ultraviolet B (290-320 nm) are an efficient therapy.

Ultraviolet B

Ultraviolet B is not toxic, and can be used as a single agent. Is usually combined with lubricants.  Ultraviolet B lamps TL01 (311-313nm)  are particularly efficient in psoriasis which resist to topic treatments.

P+UVA therapy (Psolaren + UVA)

PUVA therapy is used for :

  • Psoriasis guttata
  • Psoriasis vulgaris
  • Inverted psoriasis

The patients take orally psoralen (8-methoxypsoralen, 5-mehoxypsoralen and trioxalen,) which have a photosensitive action, and after two hours the patient is irradiated with ultraviolet arrays. Psoralen intercalate into DNA , inhibiting DNA replication and thus, inhibiting epidermal cell hyperproliferation. The free radicals formation cause a damage to cell membranes, as well as in cytoplasmic contents and to the nucleus of epidermal cells, so inhibiting cell growth. PUVA therapy is administered 2-4 times a week for 4-8 weeks (almost 20 sessions). SIDE EFFECTS of PUVA therapy can be: constipation diarrhea, nausea, vomiting, itching, erithema. And a prolongued use of psoralen can lead to cataracts, and skin cancer.

PUVA therapy increases the apoptosis of activated T-Cells.

New therapies

The monoclonal antibody anti-IL-12/13 and adalimumab (which binds specifically to TNF-α and blocks its interaction with the p55 and p75 cell surface TNF receptors) is not yet been approved but is on pre marketing study.


 

TABLE 3.2 Therapy of psoriasis related to the severity.

THERAPY DRUGS
 

 

 

 

Topic > 20% BSD

 

 

 

EMOLLIENTS

VASELINE

VITAMIN D DERIVATIVES

CALCIPOTRIOL

TACALCITOL

RETINOID

TAZAROTEN

CORTICOSTEROIDS

 

 

 

 

 

 

 

 

Systemic < 20% BSD

 

 

RETINOIDS

ACITRETIN

METHOTREXATE

CICLOSPORIN

FUMARIC ACID DERIVATIVES

BIOLOGICAL MOLECULES

1st group: (TNF-α target)

INFLIXIMAB

ETANERCEPT

ADALIMUMAB

2nd group: (T-limphocytes blockers)

EFALIZUMAB

 

 

Phototherapy

 

 

ISOTRETIONIN

TRIAMCINOLONE ACETONIDE

 

TABLE 3.2 Therapy costs

THERAPY TWELVEMONTHLY COSTS
STEROIDS 500,00€/2.000,00€
DOVONEX 2.000,00€/8.000,00€
UVB 2.000,00€
PUVA 3.500,00€
SORIATANE 6.500,00€
METHOTREXATE 1.500,00€/2.500,00€
CYCLOSPORINE 5.000,00€
BIOLOGICAL MOLECULES 10.000,00€/15.000,00€