Psoriasis part2

PSORIASISpart 2

TREATMENT OF PSORIASIS

General measures

• Assurance.

• Avoidance of psoriasis triggers.

• Daily baths Helps to remove scales and calm inflammation. Avoid harsh soaps preferably use medicated soap.

TREATMENT

FACTORS INFLUENCING SELECTION OF TREATMENT:

1. Age: childhood, adolescence, young adulthood, middle age, >60 years.

2. Type of psoriasis: guttate, plaque, palmoplantar pustular psoriasis, generalized pustular psoriasis, erythrodermic psoriasis.

3. Site: localized to palms and soles, scalp, anogenital area, scattered plaques.

4. Severity of psoriasis: mild, moderate or sever.

5. Previous treatment: ionizing radiation, systemic glucocorticoids, photochemotherapy (PUVA), cyclosporine A (CsA), and methotrexate (MTX) & their responsiveness.

6. The impairment of quality of life. The visibility of the lesions and symptoms such as pruritus.

7. Associated medical disorders (e.g., HIV) that exist or might develop.

• To date, no treatment has been shown to cure psoriasis.

• The management of psoriasis requires individualization of therapy,

• Treatments that are given as either mono—or combined—or rotational therapy.

• Combination therapy denotes the combination of two or more modalities, while rotational therapy denotes switching the patient after clearing and a subsequent relapse to another different treatment.

• In practice most patients receive combination therapy.

TREATMENT

TREATMENT

Several key points in the cascade of events that lead to psoriasis can be targeted for interventional therapy. These include:

1. Disruption of lymphocyte trafficking that leads to migration of activated T cells from endothelial cells into the epidermis and dermis.

2. Inhibition of APC presentation and subsequent T-cell activation and proliferation.

3. Prevention of Th1 cytokine production and release following T-cell activation.

4. Direct antagonism of Th1 cytokine responses.

5. Augmentation of Th2 cytokine responses.

6. Anti-Hyperproliferative effect of epidermal cells.

A.Topical B.PhototherapyC.SystemicD.Climatotherapy

TREATMENT

A. TOPICAL THERAPY

A. TOPICAL THERAPY

INDICATIONS OF TOPICAL THERAPY:1. Mild to moderate involvement, topical treatments are the first

choice.

2. Widespread involvement may also be treated with a topical agent; however, a high degree of compliance is required and this can be difficult to achieve.

3. Combination therapy is advised for the vast majority of patients, thereby efficacy and side effects.

4. Long-term form of maintenance Daily use of a topical vitamin D3 analogue (below the maximum allowed weekly dosage) provides a safe therapy (if needed). If the therapeutic response is insufficient, intermittent application of a topical corticosteroid (once or twice weekly) is helpful.

A. TOPICAL THERAPY

1. Vitamin D3 analogues2. Local corticosteroids3. Anthralin (Dithranol)4. Topical retinoids5. Salicylic acid6. Coal tar7. Calcineurin inhibitors8. Emollients

1. Vitamin D3 Analogues

• Vitamin D3 analogues inhibits epidermal proliferation, and it induces normal differentiation by enhancing cornified envelope formation and activating transglutaminase; it also inhibits several neutrophil functions.

• Potent topical corticosteroids are superior to calcipotriene. But calcipotriene was more effective than coal tar or Anthralin.

• Due to their therapeutic efficacy, cosmetic acceptability and limited toxicity, calcipotriene (calcipotriol) and other vitamin D3 analogues have become a first-line therapy of mild to moderate psoriasis. Also first-line therapy for mild to moderate juvenile psoriasis.

• The efficacy of calcipotriene is not reduced with long-term treatment.


• Calcipotriene is applied twice daily.• Salicylic acid inactivates calcipotriene.• When the amount used does not exceed the

recommended, calcipotriene can be used with a great margin of safety.

• It is often used in combination with or in rotation with topical corticosteroids in an effort to maximize therapeutic effectiveness while minimizing steroid-related skin atrophy.

• When calcipotriene and betamethasone dipropionate are combined, an ~70% reduction in PASI has been observed (ointment formulation) bas has clearing/minimal disease in ~70% of patients with scalp psoriasis (gel formulation).

• Other vitamin D analogues are tacalcitol and maxacalcitol.


2. Local corticosteroids

• They are commonly first-line therapy in mild to moderate psoriasis and in sites such as the flexures and genitalia (need low potency products to avoid SE), where other topical treatments can induce irritation.

• Maximum improvement usually achieved within 2 wks.

• Improvement is usually achieved within 2 to 4 weeks, then maintenance is achieved by use in the weekends only.

• Topical steroids under occlusion do have a limited place in the management of recalcitrant psoriasis of the scalp, hands, feet and other areas.

• Potent preparations are likely to be needed on the scalp and knuckles particularly.


• Tachyphylaxis (decrease in efficacy with time) and/or rebound of topical steroids in psoriasis is well-established.

• Long-term topical steroids may cause adrenal suppression.

• Intensive treatment with the most potent preparationscan induce generalized pustular or erythrodermic psoriasis.

• Because of these side effects potent topical steroids e.g. clobetasol may be used on alternate day basis.

• Intermittent treatment schedules (e.g. once every 2 or 3 days or on weekends) are advised for more prolonged treatment courses.

• To avoid systemic effects of class I glucocorticoid, a maximum of 50 g oit. may be used /w.

• Corticosteroids are manufactured in various vehicles, from ointments, creams and lotions to gels, foams and shampoos. Ointment formulations, in general, have the highest efficacy.

• For small plaques (< 4 cm) or nail matrix in cases of severe psoriatic nails, triamcinolone acetonide aqueous suspension 3-10 mg/mL diluted with normal saline is injected into the lesion intradermally.


3. Dithranol (Anthralin )

• It is a anthracene derivative which is extracted from coal tar.

• It is made up in a cream, ointment, or paste.• It has an anti-hyperproliferative effect, also inhibits

mitogen-induced T-lymphocyte proliferation and neutrophil chemotaxis.

• It is mainly used on plaques resistant to other therapies.

• Anthralin can be combined with UVB phototherapy with good results using the INGRAM REGIMEN.

• Treatment usually in an inpatient setting or day-care center. If the anthralin treatment is performed at home, the efficacy is substantially less.


• Classic anthralin therapy starts with low concentrations (0.05 to 0.1 %) incorporated in petrolatum or zinc paste combined with salicylic acid 1% and given once daily. The concentration is weekly in individually adjusted increments up to 4 % until the lesions resolve.

• Most common side effects are: 1. Irritant contact dermatitis 2.Staining of clothing, skin, hair, and nails.


4. Topical retinoid-Tazarotene

• It is a third-generation retinoid.• It is available in 0.05 % and 0.1 % gels, and a

cream.• Selectively binds Retinoic Acid Receptor (RAR)-

β and RAR-γ.• Tazarotene has been shown to epidermal

hyper-proliferation and it inhibits psoriasis-associated differentiation (e.g. transglutaminase expression and keratin 16 expression).

• It reduces mainly scaling and plaque thickness, with limited effectiveness on erythema.

4. Topical retinoid-Tazarotene

4. Topical retinoid -Tazarotene

• When used as a monotherapy, a significant proportion of patients develop local irritation, burning & erythema (especially with the 0.1% formulations).

• Efficacy can be enhanced by combination with mid- to high-potency steroids or UVB phototherapy but it has been recommended that UV doses be reduced by at least one-third if tazarotene is added in the middle of a course of phototherapy.

5. Salicylic acid

• If the psoriatic plaques have thick scale, this needs to be reduced to enhance penetration of topical medications and ultraviolet (UV) light.

• Salicylic acid 5–10% has a substantial keratolytic effect and, in the case of scalp psoriasis,

• Salicylic acid can be formulated in an lotion, shampoo, oil or ointment base.

• Application of salicylic acid to localized areas can be done daily, but, for more widespread areas, two to three times per week is preferred. This is to prevent systemic intoxication especially in infants or those with reduced renal function.

6. Coal Tar

• The use of tar to treat skin diseases dates back nearly 2000 years.

• Tar is the dry distillation product of organic matter heated in the absence of oxygen.

• Exactly how coal tar works to treat these conditions is not completely understood. It appears to have antimicrobial, anti-inflammatory, photosensitizing actions and is effective as an antipruritic.

• Coal tar, in concentrations 5- 33% can be compounded in creams, ointments, shampoos and pastes.

• Although crude coal tar may be the most effective tar available for the treatment of psoriasis, a distilled products are also used.

6. Coal Tar

• It is often combined with salicylic acid (2-5%) keratolytic action leads to better absorption of the coal tar.

• In 1925, Goeckerman introduced “THE GOECKERMAN TECHNIQUE” which uses crude coal tar and UV light for the treatment of psoriasis.

6. Coal Tar

DISADVANTAGES OF COAL TAR: 1. Allergic reactions.2. Folliculitis.3. Unwelcome smell and appearance.4. Stain clothing and other items. 5. Carcinogenic (controversy).6. It has mutagenic potential, tar is contraindicated in pregnant

or lactating women.

6. Coal Tar

7. Topical Calcineurin Inhibitors

• Agents: Tacrolimus & Pimecrolimus.

• They inhibit calcineurin, thus blocking both T-lymphocyte signal transduction and IL-2 transcription.

• They are not effective in plaque psoriasis. However, pimecrolimus for treatment of inverse and seborrheic dermatitis-like psoriasis of the face and ear canals.

• The main side effect of these medications is a burning sensation at application site.

• Anecdotal reports of lymph node or skin malignancy require further evaluation in controlled studies, and these drugs have a U.S. Food and Drug Administration (FDA) “black box warning”.

8. Emollients

• Between treatment periods, skin care with emollients should be performed to avoid dryness.

• Emollients reduce scaling, may limit painful fissuring, and can help control pruritus.

• They are best applied immediately after bathing or showering.

• The use emollients in combination with topical treatments improves hydration while minimizing treatment costs.

B. PHOTOTHERAPY

• Photo(chemo)therapy represents a mainstay in the treatment of psoriasis.

• Phototherapy with broadband or narrowband ultraviolet B (UVB) and photochemotherapy with ultraviolet A (UVA) following ingestion of or topical application of a psoralen are classic treatment options.

• INDICATIONS: Moderate to severe psoriasis: first-line treatment as monotherapy or in combination.

• The investigators also developed practice guidelines and recommended the following sequence of therapies: UVB, PUVA, methotrexate, acitretin and then cyclosporine.

B. PHOTOTHERAPY

B. PHOTOTHERAPY

1. NB-UVB2. PUVA3. Excimer Laser

Dosing

Excimer laser PUVA NB-UVB

•2-6 MED twice weekly

•Initial dose 0.5-2.0 J/cm2, depending on skin type followed by twice weekly•Increase dose by 40% per week until erythema, then maximum 20% per week until a maximum of 15 J/cm2

•Initial dose at 70% of MED followed by 3 treatments /w •Lubricate before session•Increase dose by at least 10-20% of the MED

Excimer laser PUVA NB-UVB

•As NB-UVB 1. Genetic disorders characterized by increased photosensitivity or an risk of skin cancer.

2. Melanoma, and nonmelanoma skin cancers

ABSOLUTE CONTRAINDI

-CATIONS

3. High cumulative number of PUVA treatments, i.e. >200-300 individual treatments (PUVA)

4. Pregnancy or lactation5. Impaired liver function or

hepatotoxic medication 6. Treatment with cyclosporine

•As NB-UVB 1. Skin type I2. Photosensitive dermatoses3. Unavoidable phototoxic systemic or topical medications 4. Immunosuppressive medication5. Previous history of arsenic exposure, ionizing irradiation 6. Age < 10 yr, 7. Seizure disorder (risk of fall/injury)

RELATIVE CONTRAINDI

-CATIONS8. Cataracts9. Men and women in reproductive

years without contraception

Devices used

Devices used

Excimer Laser

The 308 nm excimer laser can be used to treat a limited number of plaques in patients with localized disease.

C. SYSTEMIC THERAPY

C. SYSTEMIC THERAPY

• Can be used when other modalities fail to achieve desirable response.

• The concept of rotational therapies is valuable.

• Cyclosporine should not be used as a maintenance treatment, whereas methotrexate, acitretin and fumarates can be employed for long-term control of psoriasis.

• However, long-term use of these systemic treatments is restricted by their cumulative toxicity potential.

• If neither photo(chemo)therapy nor classic systemic medications provide adequate improvement, treatment with a biologic agent is indicated.

C. SYSTEMIC THERAPY

I. Classic (Conventional) systemic therapies:1. Methotrexate2. Acitretin3. Cyclosporine4. Other systemic therapies

II.Targeted immune modulators (“biologic” therapies)

I. Classic systemic therapies

1. Methotrexate (MTX)

1. Methotrexate (MTX)

• Structure• Pharmacodynamics• Mechanism of action• Dosage• Indications• Side effects• Monitoring• Contraindication• Drug Interactions • Toxicity & antidote

1. Methotrexate

• Is an Antimetabolite.• MTX is a first-line systemic therapy for psoriasis as it is highly

efficacious for severe disease and all clinical variants of psoriasis. • In chronic plaque psoriasis, initial improvement is observed 1-7

weeks and maximum improvement can be expected after 8–12 weeks of treatment.

• Potential side effects restrict its use to moderate to severe disease resistant to topical treatments and photo(chemo)therapy and/or situations in which these are contraindicated.

• Of the systemic medications, methotrexate is regarded as the treatment of choice in childhood psoriasis.

Structure of MTX

• Folic acid analogue

Pharmacodynamics of MTX

• MTX is not difficult to use and oral administration achieves reliable blood levels unaffected by food intake.

• MTX is widely distributed throughout the body, but penetrates the blood–brain barrier poorly.

• Within 1 hour of ingestion, distribution and active cellular uptake is complete.

• Plasma MTX is 50% protein-bound, and irreversibly bound to dihydrofolate reductase, the enzyme it inhibits.

• By 4 hours, the kidneys have excreted the plasma portion of the drug.

• Over the next 10–27 hours, the drug is slowly released from body tissues.

DHFR

Thymidylate

synthetase

Mechanism of action of MTX

1. Dihydrofolate reductase (DHFR) converts dihydrofolate to tetrahydrofolate (fully reduced folic acid), which is a necessary cofactor in the de novo synthesis of thymidylate and purine nucleotides, which, in turn, are required for DNA/RNA synthesis. MTX competitively inhibits DHFR, although this inhibition can be at least partially reduced by concomitant folic acid administration. Although originally believed to suppress keratinocyte proliferation, it is more likely that MTX inhibits DNA synthesis in immunologically active cells especially lymphocytes, circulating and cutaneous.

2. Forms polyglutamyl-MTX which traps MTX inside cell also exerts partially reversible inhibition downstream on thymidylate synthetase, inhibiting cell division in S phase. Decreases THF intracellular which decreases conversion of Deoxyuridine monophosphate (dUMP) to dTMP.

3. MTX decreases inflammation through other mechanisms as well. By inhibiting amino-imido-carboxy-amido-ribonucleotide transformylase (AICAR transformylase), MTX increases local tissue concentrations of the potent anti-inflammatory mediator adenosine.

4. By inhibiting methionine synthase (MS), MTX reduces production of the proinflammatory mediator S-adenyl methionine (SAM).

Mechanism of action of MTX

Dosage of MTX• Once-weekly dose of up to 30 mg.• Oral, IM, SC.• The starting dose 2.5–7.5 mg may be gradually

increased by 2.5 to 5 mg every 2–4 weeks until satisfactory results are obtained with minimal toxicity.

• The usual weekly dose 10–15 mg, although doses up to 25 mg per week are not uncommonly used, except in patients with renal insufficiency.

• Once disease control has been attained for at least 1–2 months, the MTX can be tapered by 2.5 mg every 1–2 weeks to the lowest dose that still maintains disease control.

• 2.5 mg tab & 25 mg/ml vial are the most commonly available forms.

Dosage of MTX• Historically; The triple-Dose (Weinstein) Regimen over 24 hours (8 a.m.

and 8 p.m. day 1, and 8 a.m. day 2). There were theoretical advantages for the divided dosing regimen from a cell cycle kinetics standpoint.

• However, since the clinical result is the same, a single dose, which is easier and less confusing (for the patient and the pharmacist), is currently recommended.

Other indications of MTX

1. CTCL

2. Dermatomyositis

3. Pityriasis rubra pilaris

4. Lupus erythematosus

5. Langerhan’s cell histiocytosis

6. Lymphomatoid papulosis

7. Localized scleroderma (morphea) & systemic scleroderma

8. PLEVA

9. Pompholx

10.Bullous Pemphigoids

Side effects of MTX

• Pancytopenia typically develops early, compared to liver fibrosis and cirrhosis, which take years to develop.

• The higher the cumulative dose of MTX, the greater the risk of significant liver damage.

• Photosensitivity may occur and patients should take appropriate sun precautions.

• Gastrointestinal intolerance & megaloblastic anemia is often reduced with concomitant folic acid therapy (1–5 mg orally daily except on day MTX administered, based on symptoms) without diminishing the efficacy of antipsoriatic treatment.

Monitoring of MTX

• Baseline & Repeat baseline tests weekly during dose escalation, then every 2 wk and later at intervals of perhaps 3 months.

• It's best to do blood tests at least 5 d. after a dose & just prior to next dose.

1. Liver enzymes 2. Complete blood count3. kidney function tests (creatinine)4. Pregnancy test5. liver biopsy: In the most recent guidelines, patients with normal

liver function tests and without a history of liver disease or alcoholism are not asked to undergo liver biopsy until they have been treated with a cumulative MTX dose of 1.0 to 1.5 g. Repeat biopsies are done approximately 1.0 to 1.5 g thereafter if liver function test and biopsy findings are normal.

Drug Interactions of MTX

• Drugs that elevate MTX blood levels include: 1. NSAIDs2. Salicylates3. Sulfonamides 4. Chloramphenicol

• Drugs also inhibit the folate metabolic pathway and markedly increase the risk for pancytopenia with concomitant use:

1. Trimethoprim2. Sulfonamides 3. Dapsone

• Systemic retinoids and alcohol may cause synergistic liver damage.

5. Phenothiazines 6. Phenytoin 7. Tetracyclines

Toxicity of MTX

• Leucovorin calcium (folinic acid) is the only antidote for the hematologic toxicity of MTX.

• When an overdose is suspected, an immediate leucovorin dose of 20 mg should be given parenterally or orally as early as possible, and subsequent doses should be given every 6 hours.

• Alkalinize urine & hydrate patient to dilute & increase solubility of metabolites.

2. Acitretin

2. Acitretin

• It is the free metabolite of etretinate.

• Acitretin is an effective treatment for psoriasis as well as disorders of keratinization.

• May contribute to improvement by normalizing keratinization and hyperproliferation of the epidermis.

• In patients with chronic plaque psoriasis, 0.5 mg/kg/day is the initial dosage, which can be increased depending upon the clinical response and side effects.

• For erythrodermic psoriasis, the initial dosage is 0.25 mg/kg/day, and in pustular psoriasis, the dose should be maximized up to 1 mg/kg/day (25-50 mg daily).

• In patients with chronic plaque psoriasis, mild cheilitis (just perceived by the patient) is the goal, whereas in patients with pustular psoriasis, a dose that causes a clinically apparent but tolerable cheilitis is an endpoint.

2. Acitretin

• The efficacy of acitretin monotherapy in chronic plaque psoriasis is limited, with approximately 70% of patients achieving a moderate or better response.

• Treatment with photo(chemo)-therapy and/or vitamin D3 analogues results in a substantial improvement in clinical response. Maximal therapeutic efficacy is reached after 2–3 months.

• Acitretin has been shown to be an effective maintenance therapy.

• As monotherapy, acitretin is highly effective in erythrodermic and pustular psoriasis. Its efficacy in nail psoriasis and psoriatic arthritis is only modest.

• The drug is category X thus teratogenicity, makes contraception mandatory in women of childbearing age during treatment and (depending on the drug half-life) for a period of 2 months to 3 years after discontinuing therapy.

• Most patients relapse within 2 months after discontinuing acitretin.

2. Acitretin

3. Cyclosporine (CsA)

3. Cyclosporine

• Is a natural cyclic polypeptide immunosuppressant isolated from a certain type of fungi.

• Highly effective treatment for the severe manifestations of psoriasis.

• Up to 90% of patients achieve clearance or marked improvement.

• It is a calcineurin inhibitor.

• Indicated in Severe psoriasis Conventional therapies (topical treatments, photo(chemo)therapy, acitretin, methotrexate) ineffective or inappropriate.

• Efficacy of cyclosporine has been demonstrated in all variants of psoriasis (including nail psoriasis), but less so for psoriatic arthropathy.

• High-dose method: 5 mg/kg daily, then taperedLow-dose method: 2 mg/kg daily, increased every 2-4 wk up to 5 mg/kg daily, then tapered.

• The improvement is observed within a few weeks.

• During longterm treatment, there are no signs of tachyphylaxis.

3. Cyclosporine

3. Cyclosporine

• In view of its nephrotoxic effects (e.g. reduced glomerular filtration rate, tubular atrophy), cyclosporine should be given for several-month courses. In elderly patients and patients with a history of hypertension, the risks of renal impairment and hypertension are increased.

• Cyclosporine can produce dramatic rapid improvement of psoriasis, but this must be balanced by the requirement for an appropriate replacement therapy, given the need to ultimately stop cyclosporine therapy.

• Cyclosporine treatment in psoriatic patients has been reported to increase the frequency of SCCs, especially in those previously treated with PUVA due to in immunosurveillance of the skin.

4. Other systemic therapies

4. Other systemic therapies(Uncommonly used)

i. Sulfasalazineii. Mycophenolate mofetiliii.Fumaratesiv.Oral calcitriol v. Hydroxyureavi.6-thioguaninevii.Apremilast (Otezla) [PDE-4i]

II. Targeted immune modulators (“biologic” therapies)

II. Biologic therapy

• They are bioengineered molecules that target specific proteins involved in the pathogenesis of immune-mediated disorders.

• For the treatment of moderate to severe psoriasis and/or psoriatic arthritis.

• Safety concerns, lack of efficacy, and inconveniences are important restrictions, in particular for long-term use of other medications. For such patients, biologic agents can provide benefit for their skin disease as well as psoriatic arthritis.

• Currently available biologics for psoriasis target either the T-cells or block the inflammatory action of cytokines.

Biologic Agents

1. Etanercept (Enbrel®)2. Infliximab (Remicade®)3. Adalimumab (Humira®)4. Ustekinumab (Stelara®)5. Alefacept (Amevive®)6. Efalizumab (Raptiva®)

Indications of Biologic therapy

Monitoring

Some tests that should be done before starting treatment with biologics:1. Liver function tests

2. CBC with differential

3. Hepatitis panel (B & C)

4. HIV testing

5. TB testing: PPD/interferon-γ release assay (IGRA) and/or chest X-ray

During treatment6. TB testing: Annually

7. Others: every 3–12 months (or as clinically indicated)

1.Etanercept (Enbrel®)

2. Infliximab (Remicade®)

3. Adalimumab (Humira®)

4. Ustekinumab (Stelara®)

Mechanism of action

Ustekinumab Adalimumab Infliximab Etanercept

•Fully human IgG1 monoclonal antibody that binds with high affinity and specificity to the p40 subunit that is shared by the heterodimeric IL-12 and IL-23 cytokines

•IL-12 has a critical role in the development of Th1 cells and NK cell activation, whereas IL-23 is necessary for the generation of Th17

•Fully human recombinant IgG1 monoclonal antibody that specifically targets TNF-α

•Chimeric IgG1 monoclonal antibody that has high specificity, affinity, and avidity for TNF-α

•Human recombinant, soluble fusion protein TNF-α receptor. Binds soluble TNF-α and neutralizes its activity.•By interacting with membrane-

bound TNF-α, the IgG1 monoclonal antibodies can also activate complement-dependent cytotoxicity (ADCC) and induce cellular apoptosis

Dosing

Ustekinumab Adalimumab Infliximab Etanercept

•Subcutaneous injection

•45 mg (if weight is ≤100 kg) or 90 mg (if weight is >100 kg) at weeks 0 and 4, then every 12 weeks.


•An initial loading dose of 80 mg is typically given, followed by 40 mg on day 8 and then 40 mg every other week.

•Only slow intravenous infusions over 2 h.

•5-10 mg/kg at weeks 0, 2, and 6 then every 8 weeks

•Faster onset of action


•25 to 50 mg twice weekly for the first 3 months followed by 50 mg weekly

•Recommended intermittent courses no longer than 24 week

Remission duration

Ustekinumab

Adalimumab

Infliximab Etanercept

Variable Unknown Highly variablebetween individuals and may depend on the initial dose given

Variable and dose-related ranging from 70-90 days

Side effects of anti-TNF-α biologics

Use in Pregnancy

Ustekinumab

Adalimumab

Infliximab Etanercept

Category B Ctegory B Ctegory B Category B

How Supplied

Ustekinumab Adalimumab Infliximab Etanercept STELARA®

•Prefilled syringes available in 45 & 90 mg strengths

•45 mg multiple-use vials.

HUMIRA ®

•40 mg prefilled syringe or autoinjector

REMICADE ® •Vial contains

100 mg lyophilized powder

ENBREL®

• Prefilled syringes available in 25 & 50 mg strengths

• 25 mg multiple-use vials.

• 50 mg autoinjectors,

Other indications for TNF-α inhibitors

1. Rheumatoid arthritis

2. Ankylosing spondylitis

3. Juvenile idiopathic arthritis (JIA)

4. Dermatomyositis

5. Neutrophilic dermatoses: Sweet syndrome/pyoderma gangrenosum

6. IBD: Crohon’s disease/ulcerative colitis

7. Behcet syndrome

8. Cutaneous lupus erythematosus

9. Autoimmune bullous diseases

10.Lichen planus

11.Hidradenitis suppurativa,

12.Multicentric reticulohistiocytosis

13.Relapsing polychondritis

14.GVHD

15.Sarcoidosis

Choice of agent to use

• Etanercept should be considered the first choice for patients with significant uncontrolled psoriatic arthritis.

• Infliximab is useful in clinical circumstances requiring rapid disease control e.g. in unstable erythrodermic or pustular psoriasis due to it very rapid onset of action and high response rate.

Beneficial combinationsfor treatment of psoriasis

1. Topical corticosteroids–other antipsoriatic treatments: in the duration of subsequent remission periods.

2. Calcipotriene–superpotent topical corticosteroids.

3. Calcipotriene–cyclosporine.

4. Calcipotriene–acitretin.

5. Calcipotriene–PUVA: marked in the cumulative dose of UVA required.

6. Etanercept (25 mg subcutaneously once weekly)–acitretin has been shown to be as effective as etanercept 25 mg subcutaneously twice weekly.

7. Phototherapy–anthralin or tar is a time-honored therapy. However, if phototherapy is optimized by using near-erythematogenic doses, the additive benefit of anthralin or tar above that of phototherapy alone has not been substantiated, although remission periods following the combination of anthralin and optimized phototherapy are prolonged.

8. Etanercept–narrowband UVB.

Contraindicated combinations

1. Cyclosporine–acitretin: accumulation of cyclosporine, because cyclosporine is inactivated by the cytochrome P450 system, which is inhibited by acitretin.

2. Cyclosporine–PUVA: occurrence of SCCs either simultaneously or sequentially.

3. Coal tar–PUVA: may induce significant phototoxic responses.

TREATMENT OF CERTAIN SITES

Scalp

• Mild (no thick plaques): Tar or ketoconazole shampoos followed by betamethasone valerate, 1% lotion; if refractory, clobetasol propionate, 0.05% scalp application.

• Severe (Thick, adherent plaques): Removal of scales from plaques before active treatment by 10-20% salicylic acid in mineral oil, covered with a plastic cap and left on overnight.

• After shedding of scales, Intermittent use of potent and ultrapotent topical corticosteroids in combination with calcipotriene lotion with the scalp covered with plastic or a shower cap, left on overnight or for 6 h.

• When the thickness of the plaques is reduced, clobetasol propionate, 0.05% lotion, can be used for maintenance. If unsuccessful or rapid recurrence or if associated with generalized psoriasis, consider systemic treatment.

• Some formulations such as foams and solutions are easier to use in the scalp than either creams or ointments.

Scalp

Nails

• Injection of the nail fold with intradermal triamcinolone acetonide (3 mg/mL) is effective but painful and impractical when all nails are involved.

• PUVA is somewhat effective when administered in special hand-and-foot lighting units providing high-intensity UVA.

• Long-term systemic retinoids (acitretin, 0.5 mg/kg) are also effective, as are systemic MTX.

Flexural psoriasis

• Initiate therapy with topical steroids but as these are atrophy-prone regions, steroids should be applied for only limited periods of time;then switch to topical vitamin D3 derivatives or tazarotene or topical tacrolimus or pimecrolimus. If resistant or recurrent, consider systemic therapy.

• In these sensitive areas, tacalcitol and calcitriol tend to result in less irritation as compared to calcipotriene; the use of ultrapotent corticosteroids should be avoided.

Guttate Psoriasis

• Treat streptococcal infection with antibiotics.

• Narrow-band UVB irradiation is the most effective. If it fails, try PUVA

Generalized Pustular Psoriasis

• Patients should be hospitalized and treated in the same manner as patients with extensive burns.

• Rapid suppression and resolution of lesions is achieved by oral retinoids (acitretin, 50 mg/d). Supportive measures should include fluid intake, IV antibiotics to prevent septicemia, cardiac support, temperature control, topical lubricants, and antiseptic baths.

• Systemic steroids to be used only as rescue intervention as rapid tachyphylaxis occurs.

Psoriatic Arthritis

• MTX, once-a-week schedule as outlined above.

• Infliximab or etanercept are highly effective.

D. CLIMATOTHERAPY

D. Climatotherapy

• Combination of graded solar exposure and the application of mud (pelotherapy) or crude coal tar along with a spa-like experience.

REFERENCES

• Psoriasis and psoriatic arthritis: Dr Arvind Kaul, Royal Free Hospital

• Bolognia 3rd ed

• http://dermnetnz.org

• Google images

THANK YOU

Health & Medicine

Psoriasis part2