Psoriasis

Definition
• Psoriasis, a term derived from the Greek word “psora” which means “ itch”

• Psoriasis is a non-infectious, immune-mediated, proliferative, chronic

inflammatory disease of the skin and joints, characterised by well-
demarcated, thickened erythematous scaly plaques (epidermal), with a
predilection for the extensor surfaces and scalp, and a chronic fluctuating
course.

• Common sites affected include the scalp, buttocks, elbows, knees and nails.

• There are two epidemiological patterns of psoriasis, sometimes referred to

as type 1 and type 2.

– The first has an onset in the teenage and early adult years, often with a family
history of psoriasis and an increased prevalence of the HLA group Cw6.

– The onset of the second is in the fifties or sixties, when a family history is less
common and HLA Cw6 is not so prominent.
 Histopathology of Psoriasis
• Epidermis is thickened (acanthosis), with a thickened upper horny layer
(hyperkeratosis) which is reflected by the clinical features of thick, scaly
skin. Epidermal turnover (proliferation) in psoriatic skin is increased.

• In dermis, the capillaries are dilated, tortuous and closer to the surface of the
skin. This explains Auspitz's sign which is the appearance of pinpoint
bleeding after scraping off psoriasis scales.

• Inflammatory cells are present in all layers of psoriatic skin; granulocytes are
predominant and form microabscesses in the epidermis.

• T-cells, dendritic cells and cytokines such as TNFα, IL-12 and IL-23 all
contribute to its pathogenesis.
 Histopathology of Psoriasis

There are two key pathophysiological features in psoriatic plaques:

 The keratinocytes hyperproliferate with a grossly increased mitotic index

and an abnormal pattern of differentiation, leading to the retention of nuclei in
the stratum corneum, not normally present as the stratum corneum cells are
dead.

 There is a large inflammatory cell infiltrate.

 Histopathology of Psoriasis

• The transit time, i.e. the time it takes for keratinocytes in the basal layer to
leave the epidermis, is shortened in psoriasis from perhaps 28 to 5 days, so
that, cells that are not fully mature or functional reach the stratum
corneum prematurely.

• The non-plaque skin also shows an elevated rate of proliferation, but this is
modest. The nails of patients with psoriasis, even when clinically
unaffected, grow more quickly.

• The evidence implicating a key role for an immune pathogenesis includes

the association with HLA Cw6;
 Etiology
Factors thought to precipitate exacerbations are:
Trauma
• Lesions appear in areas of skin damage such as scratches or surgical
wounds (Koebner phenomenon) when the condition is erupting
Infection
• β-haemolytic streptococcal throat infections, HIV infection
Sunlight
Drugs
• Antimalarials, β-blockers, NSAIDs, tetracyclines and lithium
• ‘Rebound’ after systemic corticosteroids or potent local corticosteroids are
stopped
Emotion
• Anxiety, stress
Alcohol and smoking
• Excess alcohol consumption may exacerbate established psoriasis.
Smoking is strongly associated with psoriasis.
 Clinical presentation
• Most psoriatic lesions are asymptomatic, but not always.

• The primary psoriatic lesion is a relapsing eruption of scaling papules that

rapidly coalesce or enlarge to form circumscribed, erythematous, scaly,
plaques.

• The scale is adherent and silverywhite, and may reveal bleeding points
when removed, called the Auspitz sign.

• Scales can become extremely dense on the scalp or macerated and dispersed
in intertriginous areas.

• The development of lesions of active psoriasis at the site of epidermal

trauma is known as the Koebner phenomenon.

• The elbows, knees, scalp, gluteal cleft, fingernails, and toenails are favored
areas of involvement.
 Clinical presentation
• Extensor surfaces are affected more than the flexor surfaces, but the
disease usually spares the palms, soles, and face.

• Nail beds may show punctate pitting, profuse collections of keratotic

material, yellow-brown discoloration (“oil spot”), or onycholysis (nail
plate separation), subungual debris which may be helpful in making
the diagnosis.

• Psoriatic arthritis is a inflammatory arthritis that occurs in

approximately 25% of all patients with psoriasis, with combined
features of both rheumatoid arthritis and the seronegative
spondyloarthropathies.
 Guttate psoriasis
Psoriasis vulgaris (chronic plaque
psoriasis) • more commonly seen in children and
• predilection for scalp, elbows, young adults
and knees. • characterised by a widespread scaly
• Symmetric, sharply demarcated eruption of small ‘teardrop-like’ scaly
erythematous plaques with plaques.
silvery scales that when • predilection for trunk.
scratched off reveals punctate • classically occur after 10–14 days after
blood droplets (Auspitz sign). β-hemolytic streptococcal pharyngitis

Palmoplantar psoriasis Erythrodermic Psoriasis

Mild to severe forms The most severe form of the disease.
Well demarcated erythematous
plaque with silver scales (palms A condition of acute inflammatory
and soles) erythema and scales involving greater
Cracking, fissures, or bleeding than 90% of the BSA. (systemic
may be seen. involvement)
Pustular variant also found
(common in smokers)
Flexural psoriasis/Inverse psoriasis Psoriatic arthropathy
• Psoriasis can occur at flexural sites such • There are five patterns of
as the axillae, groin, submammary areas psoriatic arthropathy;
and genitalia.
– monoarthopathy,
– rheumatoid arthritis-like,
• Due to friction and moisture within – osteoarthritis-like,
skin folds, lesions differ in appearance
– sacroiliitis-like and
from classical psoriasis and tend to be
– arthritis mutilans.
red and glazed rather than scaly.
• Rheumatoid factor is negative in
• Secondary infections, particularly with
these patients.
Candida are common.

PUSTULAR PSORIASIS
initial stinging and burning in area may promote scratching, followed by
eruption of sterile pustules
There are two varieties of pustular psoriasis.
The generalised form is rare but serious. The onset is usually sudden, with
large numbers of small sterile pustules erupting on a red base. (systemic
symptoms)
A localised form, which primarily affects the palms and soles, is more
common.
 Diagnosis
Diagnosis is mainly based on clinical presentation.

Investigations
• SPECIAL (not typically performed)
• MICROBIOLOGY: Throat swabbing for streptococci (if guttate psoriasis)
• SKIN BIOPSY (rare)
 Management
General management of psoriasis
• Explanation, reassurance and instruction are vital.

• Patients may be very distressed by their appearance and doctors should be

aware of the impact that psoriasis can have.

• Parents may admit that they cannot take their young children swimming
because of the alarm their rash causes to other swimmers.

• Similarly, blood on bed sheets and the ubiquitous scale on bedclothes and
carpets may adversely affect personal relationships.

• In the vast majority of cases, psoriasis is not life threatening and

therefore, if the treatment is worse than the disease, it should be stopped.

• Patients should be encouraged to share decision-making about treatment

with their physician.
 Treatment categories in Psoriasis

Topical agents Systemic agents

Methotrexate
Emollients
Retinoids
Corticosteroids
Immunosuppressives, e.g.
Vit. D agonists
Ciclosporin, Mycophenolate
‘Weak’ tar or
Dithranol preparations
Newer ‘biological’ agents, e.g.
Infliximab, Etanercept
 provide symptomatic relief

 minimize required doses of systemic

Phototherapy
medications, and
UV therapies
 may even be psychologically cathartic • UV-B radiation or
for some patients • 8-methoxy PSORALEN + UV-A
(PUVA)
 Choice of Therapy
• For most patients, the initial decision point around therapy will be
between topical and systemic therapy. However, even patients on systemic
therapy will likely continue to need some topical agents.

• For purposes of treatment planning, patients may be grouped into

categories
– mild-to-moderate and
– moderate-to-severe disease.

• The location of the disease and the presence of psoriatic arthritis affect
the choice of therapy.

• Psoriasis of the palm, sole, or face can be debilitating functionally or

socially and may deserve a more aggressive treatment approach. 
 Mild to moderate Psoriasis
• Limited plaque psoriasis responds well to topical corticosteroids
(triamcinolone, fluocinolone, fluocinonide, and clobetasol) and
emollients.

• Alternatives include vitamin D analogs, such as calcipotriene

and calcitriol, tar, and topical retinoids (tazarotene).

• Localized phototherapy is another option for recalcitrant disease.

• Combinations of potent topical corticosteroids and either calcipotriene, 

calcitriol,  tazarotene, or UVB phototherapy are commonly prescribed by
dermatologists.

• Calcipotriene in combination with topical corticosteroids is highly effective

for short-term control. Calcipotriene alone can then be used continuously
and the combination with potent corticosteroids used intermittently (on
weekends) for maintenance.
 Moderate-to-severe Psoriasis
• Moderate-to-severe psoriasis is typically defined as involvement of more
than 5 to 10% of the body surface area.
OR
Involvement of the face, palm or sole, or disease that is otherwise disabling.

• These patients are candidates for phototherapy or systemic therapy,

since application of topical agents to a large area is not usually practical or
acceptable for most patients.

• Established therapies such as methotrexate and phototherapy continue to

play a role in the management of moderate to severe plaque psoriasis.

• There is ample evidence of efficacy of the newer systemic therapies

("biologics"); however, cost is a major consideration with these agents.
 Severe Psoriasis

• Severe disease — Severe psoriasis requires phototherapy or systemic

therapies such as Retinoids, Methotrexate, Cyclosporine, Apremilast, or
Biologic immune modifying agents.

Biologic agents used in the treatment of psoriasis include the Anti-TNF

agents adalimumab, etanercept, infliximab
 DRUGS USED IN PSORIASIS-Topical agents
TOPICAL THERAPIES — Patient adherence may be the largest barrier to
treatment success with topical therapies ; early patient follow-up (within a
week of initiating treatment) may improve adherence.
Emollients — 
• Hydration and emollients are valuable and inexpensive adjuncts to
psoriasis treatment.

• Keeping psoriatic skin soft and moist minimizes the symptoms of itching
and tenderness.

• Additionally, maintaining proper skin hydration can help prevent irritation

and thus the potential for subsequent Koebnerization (development of
new psoriatic lesions at sites of trauma).

• The most effective are ointments such as Petroleum jelly or thick creams,
especially when applied immediately after a hydrating bath or shower.
 DRUGS USED IN PSORIASIS-Topical agents
• Topical Corticosteroids — remain the mainstay of topical psoriasis
treatment despite the development of newer agents.

• Corticosteroids exert anti-inflammatory, antiproliferative, and

immunosuppressive actions by affecting gene transcription.

• In practice, the efficacy/potency of a topical corticosteroid is dependent on

many factors including skin type, plaque thickness, and, perhaps most
importantly, compliance.

• The typical regimen consists of twice daily application of topical

corticosteroids. Most patients will show a rapid decrease in inflammation
with such therapy, but complete normalization of skin or lasting remission is
unpredictable.

• Topical corticosteroids generally can be continued as long as the patient has

thick active lesions. Once clinical improvement occurs, the frequency of
application should be reduced.
 DRUGS USED IN PSORIASIS-Topical agents
• To minimize adverse effects and maximize compliance, the site of
application needs to be considered in choosing the appropriately potent
corticosteroid:
• On the scalp or in the external ear canal,
– potent corticosteroids in a solution or foam vehicle (eg, FLUCINONIDE 0.05%
or CLOBETASOL propionate 0.05%) are frequently indicated.
– Clobetasol 0.05% shampoo or spray can also be used for scalp involvement.

• On the face and intertriginous areas,

– a low potency cream (eg, Hydrocortisone 1%) is often sufficient.

• For thick plaques on extensor surfaces,

– potent preparations (eg, Betamethasone 0.05% or Clobetasol propionate 0.05%) are
often required.

• The risks of cutaneous and systemic side effects associated with chronic
topical corticosteroid use are increased with high potency formulations.
• For patients in whom lesions recur quickly, topical corticosteroids can be
applied intermittently (such as on weekends only) to maintain
improvement.
 DRUGS USED IN PSORIASIS-Topical agents
Topical vitamin D analogs 
– Calcipotriene (calcipotriol) 
– Calcitriol
• Calcipotriene — Calcipotriene is an established therapy in psoriasis. The
precise mechanism is not clear, but has hypoproliferative effect on
keratinocytes.

• Calcipotriene is available as a cream, solution, ointment, or foam, or as a

combination ointment, suspension, or foam with betamethasone
dipropionate.

• Topical calcipotriene may be used as an alternative or adjunct to topical

corticosteroid therapy.

• It is applied twice daily when used as monotherapy. Acidic products can

inactivate topical calcipotriene, and some topical corticosteroids may be
acidic. A reasonable approach to combination therapy is to have patients
apply topical calcipotriene and topical corticosteroids each once daily at
different times of day.
 DRUGS USED IN PSORIASIS-Topical agents
Other than skin irritation, side effects of topical calcipotriene are usually
minimal; the risk of hypercalcemia is low when the drug is used
appropriately.

Calcitriol — 
• The mechanism of action of is thought to be similar to that of calcipotriene
and involves the drug's ability to inhibit keratinocyte proliferation and
stimulate keratinocyte differentiation.
• In addition, calcitriol inhibits T-cell proliferation and other inflammatory
mediators.
• Topical calcitriol ointment appears to induce less irritation in sensitive areas
of the skin (eg, skin folds) when compared with calcipotriene.

Topical Retinoids - Tazarotene 

• The 0.1% cream was somewhat more effective, but with a slightly higher rate
of local side effects.
• Irritation limits use of tazarotene; the irritation is reduced by concomitant
treatment with a topical corticosteroid.
 DRUGS USED IN PSORIASIS-Topical agents
Tar — 
• The precise mechanism of action of tar is not known; it has an apparent
antiproliferative effect.

• Tar can be helpful as an adjunct to topical corticosteroids.

• A commonly used compound is 2% or 3% crude coal

tar in triamcinolone cream 0.1% applied twice daily to individual plaques.

• Topical tar preparations, including shampoos, creams, and other

preparations, can be used once daily. Tar shampoo should be left in place
for 5 to 10 minutes before rinsing it out.

• Patients should be warned that tar products have the potential to stain
hair, skin, and clothing. Patients may also find the odor of tar products
unpleasant.
 DRUGS USED IN PSORIASIS-Topical agents
• Calcineurin inhibitors — 

• Topical TACROLIMUS 0.1% and PIMECROLIMUS 1% are effective in the

treatment of psoriasis.

• Topical  tacrolimus and pimecrolimus  are generally well tolerated when

used to treat facial and intertriginous psoriasis. However, corticosteroid
therapy may be more effective, at least compared with pimecrolimus.

• In 2005, the US Food and Drug Administration (FDA) issued an alert about a
possible link between topical calcineurin inhibitors and cases of lymphoma
and skin cancer in children and adults, and in 2006 placed a "black box"
warning on the prescribing information for these medications.
 DRUGS USED IN PSORIASIS-Topical agents
Topical Anthralin — also known as DITHRANOL

• The mechanism of action of anthralin in psoriasis is not well understood, but may
involve anti-inflammatory effects and normalization of keratinocyte differentiation.

• Skin irritation is an expected side effect of anthralin that can limit its use. This side
effect and the ability of anthralin to cause permanent red-brown stains on clothing
and temporary staining of skin have contributed to a decline in its use.

• Application to surrounding unaffected skin should be avoided to minimize irritation.

• For patients with well-defined plaques, petrolatum or zinc oxide may be applied to

the surrounding skin as a protectant prior to application. After the desired contact
period has elapsed,  anthralin should be washed off the treated area.

• Anthralin is less effective than topical vitamin D or potent topical corticosteroid

therapy when used in outpatient setting.
 DRUGS USED IN PSORIASIS - Phototherapy
• ULTRAVIOLET LIGHT — Ultraviolet (UV) irradiation has long been
recognized as beneficial for the control of psoriatic skin lesions.

• UV radiation may act via antiproliferative effects (slowing keratinization)

and anti-inflammatory effects (inducing apoptosis of pathogenic T-cells in
psoriatic plaques).

• In choosing UV therapy, consideration must be given to the potential for UV

radiation to accelerate photodamage and increase the risk of cutaneous
malignancy.

• Modalities — Therapeutic doses of ultraviolet light can be administered in

several ways:
1. Ultraviolet B (UVB) radiation (290 to 320 nm) is used in patients with
extensive disease, alone or in combination with topical tar.
• The mechanism of action of UVB is likely through its immunomodulatory
effects. Patients receive near-erythema-inducing doses of UVB at least three
times weekly until remission is achieved, after which a maintenance regimen
is usually recommended to prolong the remission.
 DRUGS USED IN PSORIASIS - Phototherapy
2. Narrow band UVB (311 nm) is an alternative to standard UVB in the
treatment of psoriasis. Suberythemogenic doses of narrow band UVB are
more effective than broadband UVB in clearing plaque psoriasis. Apoptosis
of T cells is also more common with 311 nm than with broadband UVB.

3. Photochemotherapy (PUVA) involves treatment with either oral or bath

psoralen followed by ultraviolet A (UVA) radiation (320 to 400 nm) under
strict medical supervision.

• UVA penetrates deeper into the dermis than UVB and does not have the
latter's potential for burning the skin.

• A number of possible mechanisms have been postulated to explain PUVA's

effects . With oral PUVA, patients ingest the photosensitizing drug, 8-
methoxypsoralen, followed within two hours by exposure to UVA; this
sequence is performed three times weekly in increasing doses until
remission, then twice or once weekly as a maintenance dose.
 DRUGS USED IN PSORIASIS

• Excimer laser — Another development in ultraviolet therapy for psoriasis

involves use of a high energy 308 nm excimer laser.

• The laser allows treatment of only involved skin; thus, considerably higher
doses of UVB can be administered to psoriatic plaques at a given treatment
compared with traditional phototherapy. (hyperpigmentation (tanning) in
treated areas is a problem)
 DRUGS USED IN PSORIASIS-Systemic Therapies

• SYSTEMIC THERAPIES —  for patients with more than 10 percent body

surface area involvement or less extensive, but debilitating disease.

• Options for systemic therapy include immunosuppressive or

immunomodulatory drugs such as
– Methotrexate
– Cyclosporine
– Apremilast
– Biologic agents
– Systemic Retinoids (effects epidermal proliferation and differentiation as well as
immunomodulation)
 DRUGS USED IN PSORIASIS-Systemic Therapies
Methotrexate — folic acid antagonist

• It is also effective for the treatment of psoriasis, psoriatic arthritis and psoriatic nail disease.

• Mechanism of action is centered around the antiproliferative effects on DNA synthesis in

epidermal cells; it is also immunosuppressive on activated T-cells that controls psoriasis .

• It is usually administered in an intermittent low-dose regimen such as once weekly.

Route: oral, iv, im, or sc; Usual dose : 7.5 mg and 25 mg per week

• Folic acid, 1 mg daily, protects against some of the common side effects seen with low-dose
methorexate such as stomatitis.

• Folate does not appear to protect against pulmonary toxicity, monitoring for bone marrow
suppression and hepatotoxicity are necessary during therapy.

• Concurrent use of other medications that interfere with folic acid metabolism, such as sulfa
antibiotics, can increase the toxicity of methotrexate.

• For patients with one or more risk factors for hepatotoxicity from methotrexate, use of a
different systemic drug should be considered.
DRUGS USED IN PSORIASIS-Systemic Therapies
Systemic Calcineurin Inhibitors — 

• The T-cell suppressor Cyclosporine is effective in patients with severe

psoriasis.

• Usual doses are in the range of 3 to 5 mg/kg per day orally.

• Improvement is generally observed within four weeks.

• Close monitoring is required since renal toxicity and hypertension are

common and often limit the long-term use of cyclosporine in patients with
psoriasis. 
DRUGS USED IN PSORIASIS-Systemic Therapies
Apremilast — Phosphodiesterase 4 Inhibitor

• Phosphodiesterase 4 inhibition reduces production of multiple cytokines

involved in the pathogenesis of psoriasis.

• Apremilast  is indicated for the treatment of moderate to severe plaque

psoriasis in patients who are candidates for phototherapy or systemic
therapy.

• Apremilast is associated with a short-term risk of diarrhea, especially when

treatment is started, occurring in roughly 15 to 20 percent of patients.

• Tolerability of apremilast is improved by slowly ramping up the dose when

treatment is initiated.
DRUGS USED IN PSORIASIS-Systemic Therapies
Apremilast: The recommended dose titration schedule for adults is as follows:
• Day 1: 10 mg in morning
• Day 2: 10 mg in morning and 10 mg in evening
• Day 3: 10 mg in morning and 20 mg in evening
• Day 4: 20 mg in morning and 20 mg in evening
• Day 5: 20 mg in morning and 30 mg in evening
• Day 6 and thereafter: 30 mg twice daily

• In adult patients with severe renal impairment, the recommended final dose is
30 mg once daily. At the start of therapy, only the morning dose of the above
titration schedule is given.

• Other side effects include nausea, upper respiratory infection, headache, slight

increase in risk for depression and weight loss.

• Periodic monitoring of weight is recommended.

DRUGS USED IN PSORIASIS-Systemic Therapies
Retinoids — Systemic retinoids (derivatives of Vit. A) are utilized for patients
with severe psoriasis, including pustular and erythrodermic forms, and in
patients with HIV-associated psoriasis.

• The retinoid of choice in psoriasis is Acitretin. The usual dose range of

Acitretin is 25 mg every other day to 50 mg daily.

• Acitretin can be used in combination with UVB or PUVA therapy. Used in

this way, patients have higher response rates with better tolerance and less
UV exposure.

• Monitoring for hypertriglyceridemia and hepatotoxicity are required with

retinoid therapy.

• Common side effects include cheilitis and alopecia. It is teratogenic;

Pregnancy is contraindicated for three years after discontinuing the drug.
DRUGS USED IN PSORIASIS-Systemic Therapies
• Biologic agents — TNF-alpha inhibitors –
• Effective in adult patients with moderate to severe chronic plaque psoriasis
who are candidates for systemic therapy or phototherapy.

• The available biologics for psoriasis have excellent short-term and long-term
efficacy and favorable tolerability. Examples of biologic therapies include 
– Etanercept
– Infliximab
– Adalimumab
– Ustekinumab
– Secukinumab
– Ixekizumab
– Brodalumab
– Guselkumab
• There is a concern that all TNF-alpha inhibitors have the potential to
activate latent infections such as tuberculosis.
• In addition, risk for herpes zoster may be increased in patients receiving
biologic therapy in combination with methorexate.
DRUGS USED IN PSORIASIS-Systemic Therapies
Etanercept — 
• Standard dosing for etanercept for adults is subcutaneous injection of 50 mg
twice weekly for the initial three months of therapy, followed by a 50 mg
injection once weekly for maintenance therapy.  

Infliximab — 
• The onset of action of infliximab is faster than other commercially available
biologic agents.
• Standard dosing for infliximab for adults is intravenous infusion of
5 mg/kg at weeks 0, 2, and 6, followed by every eight weeks thereafter.

Adalimumab -
• Dosing: initial subcutaneous injection of 80 mg of adalimumab followed by
40 mg given every other week, beginning one week after the initial dose.
DRUGS USED IN PSORIASIS-Systemic Therapies
Ustekinumab — targets interleukin (IL)-12 and IL-23.
• Ustekinumab is indicated for the treatment of adult patients with
moderate to severe psoriasis who are candidates for phototherapy or
systemic therapy.

Secukinumab —  an anti-IL-17

Ixekizumab — anti IL-17A

Brodalumab — an anti-IL-17 receptor

Guselkumab — is a human immunoglobulin G1 (IgG1) lambda monoclonal

antibody that binds to the p19 subunit of IL-23. The mechanism of action
in psoriasis involves downstream inhibition of IL-23 signaling.

Itolizumab, a monoclonal antibody against the T-cell , is a biologic agent

that is available for the treatment of psoriasis in India.