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Psoriasis
Introduction
●Psoriasis is a complex, chronic, multifactorial, inflammatory disease that
involves hyperproliferation of the keratinocytes in the epidermis, with an
increase in the epidermal cell turnover rate
●Environmental, genetic, and immunologic factors appear to play a role
●Characterized by red, scaly, sharply demarcated indurated papules and
plaques of various sizes
Epidemiology
●2-3% of world’s population
●Males = females
●Major susceptibility locus: 6p21 (PSORS1)
●Other loci: Chromosome 1p (PSORS7), 1q (PSORS4), 3q (PSORS5), 4q
(PSORS3), 17q (PSORS2), 19p (PSORS6)
Type I and Type II Psoriasis
Type I psoriasis Type II psoriasis
<40 years age >40 years of age
About 75% About 25%
More severe Less severe than type I
HLA – Cw6 associated Less genetic association
Positive family history Family history usually absent
Aetiology
●Environmental, genetic, and immunologic factors appear to play a role
Systemic chronic
inflammation
• Psoriasis
Immune
factors
Environmental
factors
Heredity
PSORS1
HLA-Cw6
Pathogenesis
●Two hypothesis
○Keratinocyte hyperproliferation may be due to immunological responses
■Cytokines released by lymphocytes and Langerhans cells may further stimulate the
inflammatory cells to cause an increased rate of epidermal cell turnover
○Epithelial cells themselves produce cytokines which promote proliferation of epithelial cells and
attract lymphocytes
Chapman A., El Miedany Y. (2017) Psoriasis. In: El Miedany Y. (eds) Comorbidity in Rheumatic Diseases. Springer, Cham.
Trigger Factors
●Trauma: Mechanical, chemical, radiation
●Infections: Streptococcus, staphylococcus, HIV
●Stress
●Alcohol and smoking
●Metabolic factors: Hypocalcemia
●Sunlight: Usually beneficial but in some may cause exacerbation
Trigger Factors: Drugs
Common Less common
●Beta blockers
●Lithium
●Antimalarials
●NSAIDS
●ACE Inhibitors
●Antibiotics
●Interferons
●Terbinafine
●Benzodiazepines
●Digoxin
●Clonidine
●Amiodarone
●Quinidine
●Gold
●TNF alpha inhibitors
●Imiquimod
●Fluoxetine
●Cimetidine
History
●Prominent itchy, red areas with increased skin scaling and peeling
●New lesions appearing at sites of injury/trauma to the skin (Koebner
phenomenon)
●Actual clearance of lesions following trauma to the skin (reverse Koebner
phenomenon)
●Exacerbation in winter, improvement in summer
●Significant joint pain, stiffness, deformity in 10-20%
●Family history of similar skin condition
Morphology
●Lesions: Erythematous, scaly papules and plaques
○Characteristic lesions include well-demarcated, erythematous plaques with adherent silvery
white scales
●Cardinal features: Erythema, induration and scaling
○The commonest type is psoriasis vulgaris
●Sites: Mostly extensors sites are involved
○Elbows, knees, scalp, lumbosacral areas, intergluteal clefts
○Palms/soles involved commonly
●Auspitz sign
○On scraping a lesion of psoriasis with a blunt glass slide, silvery scales are observed followed by
a glistening transparent membrane
○On removal of this membrane [Bulkeley’s membrane] multiple small bleeding points are
observed
○This sign is absent in pustular psoriasis and inverse psoriasis
●Grattage test
○While eliciting the Auspitz sign, the characteristic coherence of scales seen as if one scratches a
wax candle (candle grease sign)
Woronoff's Ring
●A blanched halo of approximately uniform width surrounding psoriatic lesions
usually following phototherapy or coal tar therapy
●Local inability to synthesize PGE2 in response to an ultraviolet light stimulus,
resulting from the presence of an inhibitor of prostaglandin synthesis
Auspitz Sign Woronoff’s Ring
Morphological Types
●Chronic plaque psoriasis:
○Most common form
○Also known as psoriasis vulgaris
○Typically appears as erythematous plaques covered with silvery white scales
○The plaques coalesce and cover large areas of skin
○Common locations include the trunk, extensor surfaces of limbs and the scalp
Chronic Plaque Psoriasis
Morphological Types
●Guttate psoriasis:
○Greek word “gutta” meaning droplet
○Characterized by numerous small oval (teardrop-shaped) spots distributed in a centripetal
fashion
○Accounts for 2% of the cases
○Associated with streptococcal (group A) throat infection
○Common in children, good prognosis
○About one third patients develop plaque psoriasis eventually
Guttate Psoriasis
Morphological Types
●Pustular psoriasis: Crops of pustules on erythematous base
1. Localized
A. Palmoplantar pustulosis
B. Acrodermatitis continua of Hallopeau
2. Generalized
A. Acute (Von Zumbusch)
B. Of pregnancy
C. Infantile and juvenile
D. Circinate
E. Localized (not hands and feet)
●Trigger factors: Sudden withdrawal of systemic or potent topical steroids,
infections
Pustular Psoriasis
Demographics of Palmoplantar Pustulosis
Differ from Other Types of Psoriasis
●Women >men (9:1)
●Peak between 40 to 60 years
●Strong association with smoking
Morphological Types
●Erythrodermic psoriasis: Generalised erythema and scaling (involving >90%
of BSA)
○Develops from chronic plaque psoriasis or unstable psoriasis precipitated by infections, tar,
drugs or withdrawal of corticosteroids
○Accompanied by fever, chills, hypothermia, and dehydration secondary to the large BSA
involvement
●Follicular psoriasis: Scaly, follicular papules over trunk and extremities
○These are present at the openings of pilosebaceous follicles
Erythrodermic Psoriasis
Morphological Types
●Linear psoriasis: Linear distribution of psoriatic lesions along Blaschko's lines
●Annular psoriasis: Clearing in the centre of the plaque
●Rupioid (limpet like or cone shaped lesions), elephantine and ostraceous
psoriasis (lesions resembling oyster shells)
○Rupoid plaques are small, 2-5 cms in diameter and highly hyperkeratotic, resembling limpet
shells
●Ostraceous psoriasis presents with hyperkeratotic plaques with concave
centres similar in shape to oyester shells
Distributional Variation
●Scalp psoriasis
●Palmoplantar psoriasis
●Nail psoriasis: Nails involved in 25-50% patients
○Pitting, onycholysis, subungual hyperkeratosis, splinter hemorrhages, the oil-drop sign
●Mucosal psoriasis
●Inverse psoriasis:
○Spares the typical extensor surfaces
○Affects intertriginous (i.e., axillae, inguinal folds, inframammary creases) areas with minimal
scaling
Scalp Psoriasis
Palmo-plantar Psoriasis
Nail Psoriasis
Inverse Psoriasis
Psoriasis in Children
●Common in girls
●More pruritic
●Lesions are relatively thinner, softer, and less scaly
●More frequently precipitated by infections
●Facial involvement more common than in adults
●Certain clinical variants like erythroderma, arthropathy and pustular psoriasis
are rare
Psoriasis in HIV
●Acute onset
●More severe
●Refractory to conventional treatment
●Poor prognosis
Psoriatic Arthritis
●Seen in 5-10% of psoriatic patients
●Types:
○Classic - Distal interphalangeal arthropathy (15%)
○Asymmetrical oligoarticular arthritis (70%)
○Symmetrical polyarthritis - Rheumatoid type (5%)
○Psoriatic spondylitis with or without sacroiliatis (5%)
○Arthritis mutilans (5%)
●Nail associated severity index (NAPSI)
○The target nail is graded for nail matrix psoriasis and nail bed psoriasis
○The sum of these two scores is the total score for that nail
○Nail matrix changes: Pitting, leukonychia, red spots in the lunula, and nail plate crumbling
○Nail bed changes: Onycholysis, splinter hemorrhages, oil drop (salmon patch), nail bed
hyperkeratosis
Scoring Systems in Psoriasis
Nail Associated Severity Index (NAPSI)
Psoriasis Area and Severity Index
Score Erythema Induration Desquamation
0 Absent Absent Absent
1 Mild Mild Mild
2 Moderate Moderate Moderate
3 Severe Severe Severe
4 Very severe Very severe Very severe
Calculation for Intensity
●The three intensity scores are added for 4 body regions to give subtotals A1,
A2, A3, A4
●Each subtotal is multiplied by body surface area represented by that region
●A1 x 0.1 gives B1
●A2 x 0.2 gives B2
●A3 x 0.3 gives B3
●A4 x 0.4 gives B4
●The percentage area affected by psoriasis is evaluated in 4 regions of the
body (head and neck, upper limbs, trunk, lower limbs)
Score Area
0 nil
1 1-9%
2 10-29%
3 30-49%
4 50-69%
5 70-89%
6 90-100%
●Each body area score is multiplied by area affected
●B1 x (0-6) = C1
●B2 x (0-6) = C2
●B3 x (0-6) = C3
●B4 x (0-6) = C4
●PASI Score = C1 + C2 + C3 + C4
Histopathology
●Parakeratosis
●Micro abscesses of Munro in the horny layer
●Absence of granular layer
●Regular elongation of rete ridges (camel-foot shaped)
●Supra papillary thinning
●Spongiform pustules of Kogoj
●Dilated and tortuous capillaries in dermal papillae
●Superficial perivascular inflammatory infiltrate
Comorbidities in Psoriasis
●Cardiovascular disease/stroke
●Metabolic syndrome
●Diabetes
●Psoriatic arthritis
●Mood disorders (anxiety, depression, suicide)
●Crohn’s disease
Differential Diagnosis
●Seborrheic dermatitis
●Nummular eczema
●Tinea corporis
●Lichen planus
●Secondary syphilis
●Pityriasis rosea
●Drug eruption
●Candidiasis/diaper dermatitis
●Tinea unguium
●Mycosis fungoides
Management of Psoriasis
●Psoriasis is a chronic disease that can have a significant effect on quality of
life
●Management involves addressing both psychosocial and physical aspects of
the disease
●Psychosocial aspects:
○Laying out reasonable aims of treatment
○Patient education
○Counselling and/or treatment with psychoactive medications
General Measures
●Avoidance of trauma or irritating agents
●Weight reduction in obese patients
●Reduce intake of alcoholic beverages
●Reduce emotional stress
●Sunlight and sea bathing improve psoriasis except in photosensitive
Topical Therapy
●Emollients
○Minimize the symptoms of itching and
tenderness
○Help prevent irritation and thus the
potential for
■Subsequent Koebnerization
●Tar
○Antiproliferative effect
○2% or 3% crude coal tar
○Alternative is 4 to 10% LCD (liquor
carbonis detergens, a tar distillate)
Goeckerman Regimen
●Goeckerman regimen: Coal tar is applied on in‐patient basis for 24 h in
combination with sub erythemogenic doses of UVB
●Modified Goeckerman regimen using coal tar applied for 5 h/day in
combination with narrow‐band UVB (NBUVB) in patients with moderate to
severe psoriasis
Topical Therapy
●Anthralin
○May restore normal epidermal
■Proliferation and keratinization
○Stains clothes, irritant
○Ingram regimen: In‐patients are treated with a tar bath, sub
erythemogenic UVB and then dithranol in Lassar’s paste applied to
plaques, starting at a concentration of 0.05–0.1% and increased
cautiously to reduce irritation up to a maximum concentration of 4%
●Salicylic acid
○Keratolytic agent
○Adjuvant to other topicals
Topical Therapy
●Topical corticosteroids
○Mainstay of topical treatment especially for plaque psoriasis
○Anti-inflammatory, antiproliferative, and immunosuppressive actions
○Can be used as monotherapy 1-2 times daily or combined with other topical agents
●Topical vitamin D analogues
○Inhibition of keratinocyte proliferation and enhancement of keratinocyte differentiation
○Calcipotriene, calcitriol, tacalcitol, maxacalcitol, becocalcidiol
Topical Therapy
●Topical retinoids
○Tazarotene (0.05%/0.1%)
○Act by normalizing abnormal keratinocyte differentiation, diminishing hyperproliferation and by
decreasing expression of inflammatory markers
●Calcineurin inhibitors
○Tacrolimus/pimecrolimus
○Act by blocking the synthesis of numerous inflammatory cytokines
○Facial and intertriginous psoriasis
UVB Phototherapy
●Indication
○Generalized psoriasis unresponsive to topicals
○Narrow band UVB is not only more effective than broad band UVB but also leads to rapid
clearance of lesions
●Dosage:
○Initial dosing according to skin type (130-400 mJ/cm2) or MED (50% of MED) [MED = minimal
erythema dose]
○Subsequent dosage increase by 15-65 mJ/cm2 or ≤10% of initial MED
○Treatment 3-5 times/week
UVB Phototherapy
●Duration of treatment
○Response observed at 8-10 treatments
○Single course is 15-20 treatments
○Maintenance therapy may prolong remission
Combination of UVB with Systemic Therapies
●Methotrexate with UVB therapy has shown potential value because of the
synergistic effects of these two therapies
●Retinoids with UVB have been extensively studied and accelerate the
response to phototherapy, reducing the cumulative dosage of UVB and the
dose of acitretin required to achieve psoriasis clearance
Targeted Phototherapy
●Excimer lasers/lamps and targeted UVB therapy selectively target affected
lesions of psoriasis while leaving unaffected skin untreated
●Highly effective, can be used for resistant localised lesions such as scalp and
palmoplantar psoriasis
PUVA Photochemotherapy
●Systemic psoralen plus ultraviolet A is indicated for adults with generalized
psoriasis who are resistant to topical therapy
●Contraindicated in patients with known lupus erythematosus, porphyria, or
xeroderma pigmentosum
●Dosage:
○8-Methoxypsoralen, 0.4-0.6 mg/kg
○Taken 1-2 hours before exposure to UVA
○Other available forms of psoralen include 5-methoxypsoralen and trimethylpsoralen
○UV protective eye wear should be worn when outdoors for 12 hours post-ingestion
○Treatment 2-3 times/week
PUVA Photochemotherapy
●Duration of treatment:
○Initial improvement frequently seen within 1 month of therapy
○Single course is 20-25 treatments
○May be repeated as indicated
●Topical PUVA therapy
○Topical PUVA is indicated for adults with psoriasis of palms and soles
○Bath PUVA is indicated for adults and children with generalized psoriasis
Combination of PUVA with Other Therapies
●Combination of topical calcipotriol with PUVA leads to a decrease in duration
of PUVA therapy along with an improved clinical response
●Combination of oral retinoids with PUVA is more effective compared with
monotherapy with either acitretin or PUVA alone
●Because patients who have previously received PUVA treatment have an
increased risk for developing SCC when subsequently treated with
cyclosporine, this combination should be avoided
●PUVA with MTX - safety questioned
Systemic Therapy
●General principles
○A BSA of 10% has been traditionally used as a prerequisite to start a systemic therapy
○However, a subset of patients with limited disease having debilitating symptoms with significant
negative affect on quality of life of patient makes a systemic approach to treatment
appropriate
Methotrexate
●Indication:
○Severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of
therapy
●Dosing:
○Weekly single oral dose total dose should not ordinarily exceed 30 mg/week
○A test dose of 2.5-5 mg is recommended
○Folate supplementation
Apremilast
●Phosphodiesterase 4 inhibitor
●New oral agent for the treatment of moderate to severe plaque psoriasis and
psoriatic arthritis
●Advantages include its oral administration, and it is anti-inflammatory rather than
immunosuppressant
●Favourable safety profile, laboratory monitoring is not required and a potentially
advantageous weight loss effect
●Gastrointestinal intolerance is the most common adverse effect – diarrhoea (18%)
and nausea (17%)
●Apremilast has potentially been associated with an increased risk of depression,
although the incidence is low – caution and close monitoring is advised in patients
with a history of depression
Cyclosporine
●Indication:
○Adult, non immunocompromised patients with severe, recalcitrant psoriasis
○Efficacy observed in erythrodermic psoriasis, generalized pustular psoriasis, and palmoplantar
psoriasis
●Dosing:
○2.5-5.0 mg/kg/d in two divided doses/day
Acitretin
●Indication:
○Adults with severe plaque type psoriasis (FDA approved)
○Rapid and impressive responses seen in patients with pustular psoriasis
●Because of a lack of significant immunosuppression, acitretin is generally
considered effective and the treatment of choice in HIV-positive patients
with severe psoriasis
●Dosing:
○10-50 mg/day given as a single dose
○Efficacy rates when used in combination with phototherapy are higher
Second Line Systemic Agents
●Azathioprine: Due to absence of data from controlled trials, it is best to
conclude that there is no good evidence that azathioprine is an effective
treatment for psoriasis
●Fumaric acid esters: Several well-designed randomized studies of fumarates
demonstrate mean PASI improvement rates of between 50% and 80% after 12
to 16 weeks of treatment
●Hydroxyurea: May be a valuable reserve drug for patients needing systemic
treatment and who are resistant to methotrexate or develop side effects
●Leflunomide: May be used in patients of psoriasis with arthritis
Second Line Systemic Agents
●Mycophenolate mofetil: Therapy of severe psoriasis probably in combination
with cyclosporin as a cyclosporin sparing agent
●Systemic steroids:
○Not to be used in the routine care of psoriasis
○Role in the management of persistent, otherwise uncontrollable erythroderma that is causing
metabolic complications
○Generalized pustular psoriasis of the Von Zumbusch type if other drugs are contraindicated or
ineffective
○Steroids may occasionally be needed, and in high dosage to control hyperacute polyarthritis
Others
●6-Thioguanine
●Tacrolimus and pimecrolimus
●Cytokines
●Protein kinase C inhibitor
●Zidovudine
●Somatostatin
●Liarazole
●Gluten free diet
●Photodynamic therapy
Biologic Agents
●Biological's use should be restricted to:
○Patients with severe disease defined by a PASI score of 10 or more (or BSA of 10% or greater
where PASI is not applicable) and DLQI of greater than 10
○Patients who have failed to respond to, or who have a contraindication to, or who are
intolerant to other systemic therapies such as cyclosporin and methotrexate
Biologic Agents
●Biological agents licensed for treatment of psoriasis vulgaris
○Etanercept, a fully human soluble p75 TNF-α receptor fusion protein
○Infliximab, a chimeric human-immune antibody to TNF-α
○Adalimumab, a fully human recombinant antibody to TNF-α
○Ustekinumab, a fully human recombinant antibody to the p40 component of IL-12/IL-23
○Alefacept, a fusion protein of lymphocyte function associated antigen-3 and IgG that inhibits T-
cell activation
○Secukinumab, an anti-IL-17A monoclonal antibody
Biologic Agents
●Infliximab is administered by IV infusion while the others are
administered by SC injection
●Biological agent of choice
○For stable disease, particularly if not too severe (e.g., PASI >10
but <20) etanercept or adalimumab
○For patients requiring rapid disease control
adalimumab or infliximab
○For patients with unstable or generalized pustular psoriasis
severe nail disease infliximab
●Ustekinumab should be reserved for use as a second-line biological
agent
Future Therapies
●Therapies targeting Th17 pathway
●Briakinumab
●Ixekizumab
●Brodalumab
●Bimekizumab
●Netakimab
●Anti TNF therapy: Certolizumab pegol
Future Therapies
●Janus kinase inhibitor: Tofacitinib
●IL-23 Inhibitors:
○Sonelokimab
○Mirikizumab
●Other molecules:
○Ponesimod
○Exenatide/liraglutide
○Deucravacitinib (tyrosine kinase 2 selective inhibitor)
○Piclidenoson (agonist of adenosine receptor)
Thank You

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PSORIASIS (1).pptx

  • 2. Introduction ●Psoriasis is a complex, chronic, multifactorial, inflammatory disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate ●Environmental, genetic, and immunologic factors appear to play a role ●Characterized by red, scaly, sharply demarcated indurated papules and plaques of various sizes
  • 3.
  • 4.
  • 5. Epidemiology ●2-3% of world’s population ●Males = females ●Major susceptibility locus: 6p21 (PSORS1) ●Other loci: Chromosome 1p (PSORS7), 1q (PSORS4), 3q (PSORS5), 4q (PSORS3), 17q (PSORS2), 19p (PSORS6)
  • 6. Type I and Type II Psoriasis Type I psoriasis Type II psoriasis <40 years age >40 years of age About 75% About 25% More severe Less severe than type I HLA – Cw6 associated Less genetic association Positive family history Family history usually absent
  • 7. Aetiology ●Environmental, genetic, and immunologic factors appear to play a role Systemic chronic inflammation • Psoriasis Immune factors Environmental factors Heredity PSORS1 HLA-Cw6
  • 8. Pathogenesis ●Two hypothesis ○Keratinocyte hyperproliferation may be due to immunological responses ■Cytokines released by lymphocytes and Langerhans cells may further stimulate the inflammatory cells to cause an increased rate of epidermal cell turnover ○Epithelial cells themselves produce cytokines which promote proliferation of epithelial cells and attract lymphocytes
  • 9. Chapman A., El Miedany Y. (2017) Psoriasis. In: El Miedany Y. (eds) Comorbidity in Rheumatic Diseases. Springer, Cham.
  • 10. Trigger Factors ●Trauma: Mechanical, chemical, radiation ●Infections: Streptococcus, staphylococcus, HIV ●Stress ●Alcohol and smoking ●Metabolic factors: Hypocalcemia ●Sunlight: Usually beneficial but in some may cause exacerbation
  • 11. Trigger Factors: Drugs Common Less common ●Beta blockers ●Lithium ●Antimalarials ●NSAIDS ●ACE Inhibitors ●Antibiotics ●Interferons ●Terbinafine ●Benzodiazepines ●Digoxin ●Clonidine ●Amiodarone ●Quinidine ●Gold ●TNF alpha inhibitors ●Imiquimod ●Fluoxetine ●Cimetidine
  • 12. History ●Prominent itchy, red areas with increased skin scaling and peeling ●New lesions appearing at sites of injury/trauma to the skin (Koebner phenomenon) ●Actual clearance of lesions following trauma to the skin (reverse Koebner phenomenon) ●Exacerbation in winter, improvement in summer ●Significant joint pain, stiffness, deformity in 10-20% ●Family history of similar skin condition
  • 13.
  • 14. Morphology ●Lesions: Erythematous, scaly papules and plaques ○Characteristic lesions include well-demarcated, erythematous plaques with adherent silvery white scales ●Cardinal features: Erythema, induration and scaling ○The commonest type is psoriasis vulgaris ●Sites: Mostly extensors sites are involved ○Elbows, knees, scalp, lumbosacral areas, intergluteal clefts ○Palms/soles involved commonly
  • 15. ●Auspitz sign ○On scraping a lesion of psoriasis with a blunt glass slide, silvery scales are observed followed by a glistening transparent membrane ○On removal of this membrane [Bulkeley’s membrane] multiple small bleeding points are observed ○This sign is absent in pustular psoriasis and inverse psoriasis ●Grattage test ○While eliciting the Auspitz sign, the characteristic coherence of scales seen as if one scratches a wax candle (candle grease sign)
  • 16. Woronoff's Ring ●A blanched halo of approximately uniform width surrounding psoriatic lesions usually following phototherapy or coal tar therapy ●Local inability to synthesize PGE2 in response to an ultraviolet light stimulus, resulting from the presence of an inhibitor of prostaglandin synthesis
  • 18. Morphological Types ●Chronic plaque psoriasis: ○Most common form ○Also known as psoriasis vulgaris ○Typically appears as erythematous plaques covered with silvery white scales ○The plaques coalesce and cover large areas of skin ○Common locations include the trunk, extensor surfaces of limbs and the scalp
  • 20. Morphological Types ●Guttate psoriasis: ○Greek word “gutta” meaning droplet ○Characterized by numerous small oval (teardrop-shaped) spots distributed in a centripetal fashion ○Accounts for 2% of the cases ○Associated with streptococcal (group A) throat infection ○Common in children, good prognosis ○About one third patients develop plaque psoriasis eventually
  • 22. Morphological Types ●Pustular psoriasis: Crops of pustules on erythematous base 1. Localized A. Palmoplantar pustulosis B. Acrodermatitis continua of Hallopeau 2. Generalized A. Acute (Von Zumbusch) B. Of pregnancy C. Infantile and juvenile D. Circinate E. Localized (not hands and feet) ●Trigger factors: Sudden withdrawal of systemic or potent topical steroids, infections
  • 24. Demographics of Palmoplantar Pustulosis Differ from Other Types of Psoriasis ●Women >men (9:1) ●Peak between 40 to 60 years ●Strong association with smoking
  • 25. Morphological Types ●Erythrodermic psoriasis: Generalised erythema and scaling (involving >90% of BSA) ○Develops from chronic plaque psoriasis or unstable psoriasis precipitated by infections, tar, drugs or withdrawal of corticosteroids ○Accompanied by fever, chills, hypothermia, and dehydration secondary to the large BSA involvement ●Follicular psoriasis: Scaly, follicular papules over trunk and extremities ○These are present at the openings of pilosebaceous follicles
  • 27. Morphological Types ●Linear psoriasis: Linear distribution of psoriatic lesions along Blaschko's lines ●Annular psoriasis: Clearing in the centre of the plaque ●Rupioid (limpet like or cone shaped lesions), elephantine and ostraceous psoriasis (lesions resembling oyster shells) ○Rupoid plaques are small, 2-5 cms in diameter and highly hyperkeratotic, resembling limpet shells ●Ostraceous psoriasis presents with hyperkeratotic plaques with concave centres similar in shape to oyester shells
  • 28. Distributional Variation ●Scalp psoriasis ●Palmoplantar psoriasis ●Nail psoriasis: Nails involved in 25-50% patients ○Pitting, onycholysis, subungual hyperkeratosis, splinter hemorrhages, the oil-drop sign ●Mucosal psoriasis ●Inverse psoriasis: ○Spares the typical extensor surfaces ○Affects intertriginous (i.e., axillae, inguinal folds, inframammary creases) areas with minimal scaling
  • 33. Psoriasis in Children ●Common in girls ●More pruritic ●Lesions are relatively thinner, softer, and less scaly ●More frequently precipitated by infections ●Facial involvement more common than in adults ●Certain clinical variants like erythroderma, arthropathy and pustular psoriasis are rare
  • 34. Psoriasis in HIV ●Acute onset ●More severe ●Refractory to conventional treatment ●Poor prognosis
  • 35. Psoriatic Arthritis ●Seen in 5-10% of psoriatic patients ●Types: ○Classic - Distal interphalangeal arthropathy (15%) ○Asymmetrical oligoarticular arthritis (70%) ○Symmetrical polyarthritis - Rheumatoid type (5%) ○Psoriatic spondylitis with or without sacroiliatis (5%) ○Arthritis mutilans (5%)
  • 36. ●Nail associated severity index (NAPSI) ○The target nail is graded for nail matrix psoriasis and nail bed psoriasis ○The sum of these two scores is the total score for that nail ○Nail matrix changes: Pitting, leukonychia, red spots in the lunula, and nail plate crumbling ○Nail bed changes: Onycholysis, splinter hemorrhages, oil drop (salmon patch), nail bed hyperkeratosis Scoring Systems in Psoriasis
  • 37. Nail Associated Severity Index (NAPSI)
  • 38. Psoriasis Area and Severity Index Score Erythema Induration Desquamation 0 Absent Absent Absent 1 Mild Mild Mild 2 Moderate Moderate Moderate 3 Severe Severe Severe 4 Very severe Very severe Very severe
  • 39. Calculation for Intensity ●The three intensity scores are added for 4 body regions to give subtotals A1, A2, A3, A4 ●Each subtotal is multiplied by body surface area represented by that region ●A1 x 0.1 gives B1 ●A2 x 0.2 gives B2 ●A3 x 0.3 gives B3 ●A4 x 0.4 gives B4
  • 40. ●The percentage area affected by psoriasis is evaluated in 4 regions of the body (head and neck, upper limbs, trunk, lower limbs) Score Area 0 nil 1 1-9% 2 10-29% 3 30-49% 4 50-69% 5 70-89% 6 90-100%
  • 41. ●Each body area score is multiplied by area affected ●B1 x (0-6) = C1 ●B2 x (0-6) = C2 ●B3 x (0-6) = C3 ●B4 x (0-6) = C4 ●PASI Score = C1 + C2 + C3 + C4
  • 42. Histopathology ●Parakeratosis ●Micro abscesses of Munro in the horny layer ●Absence of granular layer ●Regular elongation of rete ridges (camel-foot shaped) ●Supra papillary thinning ●Spongiform pustules of Kogoj ●Dilated and tortuous capillaries in dermal papillae ●Superficial perivascular inflammatory infiltrate
  • 43. Comorbidities in Psoriasis ●Cardiovascular disease/stroke ●Metabolic syndrome ●Diabetes ●Psoriatic arthritis ●Mood disorders (anxiety, depression, suicide) ●Crohn’s disease
  • 44. Differential Diagnosis ●Seborrheic dermatitis ●Nummular eczema ●Tinea corporis ●Lichen planus ●Secondary syphilis ●Pityriasis rosea ●Drug eruption ●Candidiasis/diaper dermatitis ●Tinea unguium ●Mycosis fungoides
  • 45. Management of Psoriasis ●Psoriasis is a chronic disease that can have a significant effect on quality of life ●Management involves addressing both psychosocial and physical aspects of the disease ●Psychosocial aspects: ○Laying out reasonable aims of treatment ○Patient education ○Counselling and/or treatment with psychoactive medications
  • 46. General Measures ●Avoidance of trauma or irritating agents ●Weight reduction in obese patients ●Reduce intake of alcoholic beverages ●Reduce emotional stress ●Sunlight and sea bathing improve psoriasis except in photosensitive
  • 47. Topical Therapy ●Emollients ○Minimize the symptoms of itching and tenderness ○Help prevent irritation and thus the potential for ■Subsequent Koebnerization ●Tar ○Antiproliferative effect ○2% or 3% crude coal tar ○Alternative is 4 to 10% LCD (liquor carbonis detergens, a tar distillate)
  • 48. Goeckerman Regimen ●Goeckerman regimen: Coal tar is applied on in‐patient basis for 24 h in combination with sub erythemogenic doses of UVB ●Modified Goeckerman regimen using coal tar applied for 5 h/day in combination with narrow‐band UVB (NBUVB) in patients with moderate to severe psoriasis
  • 49. Topical Therapy ●Anthralin ○May restore normal epidermal ■Proliferation and keratinization ○Stains clothes, irritant ○Ingram regimen: In‐patients are treated with a tar bath, sub erythemogenic UVB and then dithranol in Lassar’s paste applied to plaques, starting at a concentration of 0.05–0.1% and increased cautiously to reduce irritation up to a maximum concentration of 4% ●Salicylic acid ○Keratolytic agent ○Adjuvant to other topicals
  • 50. Topical Therapy ●Topical corticosteroids ○Mainstay of topical treatment especially for plaque psoriasis ○Anti-inflammatory, antiproliferative, and immunosuppressive actions ○Can be used as monotherapy 1-2 times daily or combined with other topical agents ●Topical vitamin D analogues ○Inhibition of keratinocyte proliferation and enhancement of keratinocyte differentiation ○Calcipotriene, calcitriol, tacalcitol, maxacalcitol, becocalcidiol
  • 51. Topical Therapy ●Topical retinoids ○Tazarotene (0.05%/0.1%) ○Act by normalizing abnormal keratinocyte differentiation, diminishing hyperproliferation and by decreasing expression of inflammatory markers ●Calcineurin inhibitors ○Tacrolimus/pimecrolimus ○Act by blocking the synthesis of numerous inflammatory cytokines ○Facial and intertriginous psoriasis
  • 52. UVB Phototherapy ●Indication ○Generalized psoriasis unresponsive to topicals ○Narrow band UVB is not only more effective than broad band UVB but also leads to rapid clearance of lesions ●Dosage: ○Initial dosing according to skin type (130-400 mJ/cm2) or MED (50% of MED) [MED = minimal erythema dose] ○Subsequent dosage increase by 15-65 mJ/cm2 or ≤10% of initial MED ○Treatment 3-5 times/week
  • 53. UVB Phototherapy ●Duration of treatment ○Response observed at 8-10 treatments ○Single course is 15-20 treatments ○Maintenance therapy may prolong remission
  • 54. Combination of UVB with Systemic Therapies ●Methotrexate with UVB therapy has shown potential value because of the synergistic effects of these two therapies ●Retinoids with UVB have been extensively studied and accelerate the response to phototherapy, reducing the cumulative dosage of UVB and the dose of acitretin required to achieve psoriasis clearance
  • 55. Targeted Phototherapy ●Excimer lasers/lamps and targeted UVB therapy selectively target affected lesions of psoriasis while leaving unaffected skin untreated ●Highly effective, can be used for resistant localised lesions such as scalp and palmoplantar psoriasis
  • 56. PUVA Photochemotherapy ●Systemic psoralen plus ultraviolet A is indicated for adults with generalized psoriasis who are resistant to topical therapy ●Contraindicated in patients with known lupus erythematosus, porphyria, or xeroderma pigmentosum ●Dosage: ○8-Methoxypsoralen, 0.4-0.6 mg/kg ○Taken 1-2 hours before exposure to UVA ○Other available forms of psoralen include 5-methoxypsoralen and trimethylpsoralen ○UV protective eye wear should be worn when outdoors for 12 hours post-ingestion ○Treatment 2-3 times/week
  • 57. PUVA Photochemotherapy ●Duration of treatment: ○Initial improvement frequently seen within 1 month of therapy ○Single course is 20-25 treatments ○May be repeated as indicated ●Topical PUVA therapy ○Topical PUVA is indicated for adults with psoriasis of palms and soles ○Bath PUVA is indicated for adults and children with generalized psoriasis
  • 58. Combination of PUVA with Other Therapies ●Combination of topical calcipotriol with PUVA leads to a decrease in duration of PUVA therapy along with an improved clinical response ●Combination of oral retinoids with PUVA is more effective compared with monotherapy with either acitretin or PUVA alone ●Because patients who have previously received PUVA treatment have an increased risk for developing SCC when subsequently treated with cyclosporine, this combination should be avoided ●PUVA with MTX - safety questioned
  • 59. Systemic Therapy ●General principles ○A BSA of 10% has been traditionally used as a prerequisite to start a systemic therapy ○However, a subset of patients with limited disease having debilitating symptoms with significant negative affect on quality of life of patient makes a systemic approach to treatment appropriate
  • 60. Methotrexate ●Indication: ○Severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy ●Dosing: ○Weekly single oral dose total dose should not ordinarily exceed 30 mg/week ○A test dose of 2.5-5 mg is recommended ○Folate supplementation
  • 61. Apremilast ●Phosphodiesterase 4 inhibitor ●New oral agent for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis ●Advantages include its oral administration, and it is anti-inflammatory rather than immunosuppressant ●Favourable safety profile, laboratory monitoring is not required and a potentially advantageous weight loss effect ●Gastrointestinal intolerance is the most common adverse effect – diarrhoea (18%) and nausea (17%) ●Apremilast has potentially been associated with an increased risk of depression, although the incidence is low – caution and close monitoring is advised in patients with a history of depression
  • 62. Cyclosporine ●Indication: ○Adult, non immunocompromised patients with severe, recalcitrant psoriasis ○Efficacy observed in erythrodermic psoriasis, generalized pustular psoriasis, and palmoplantar psoriasis ●Dosing: ○2.5-5.0 mg/kg/d in two divided doses/day
  • 63. Acitretin ●Indication: ○Adults with severe plaque type psoriasis (FDA approved) ○Rapid and impressive responses seen in patients with pustular psoriasis ●Because of a lack of significant immunosuppression, acitretin is generally considered effective and the treatment of choice in HIV-positive patients with severe psoriasis ●Dosing: ○10-50 mg/day given as a single dose ○Efficacy rates when used in combination with phototherapy are higher
  • 64. Second Line Systemic Agents ●Azathioprine: Due to absence of data from controlled trials, it is best to conclude that there is no good evidence that azathioprine is an effective treatment for psoriasis ●Fumaric acid esters: Several well-designed randomized studies of fumarates demonstrate mean PASI improvement rates of between 50% and 80% after 12 to 16 weeks of treatment ●Hydroxyurea: May be a valuable reserve drug for patients needing systemic treatment and who are resistant to methotrexate or develop side effects ●Leflunomide: May be used in patients of psoriasis with arthritis
  • 65. Second Line Systemic Agents ●Mycophenolate mofetil: Therapy of severe psoriasis probably in combination with cyclosporin as a cyclosporin sparing agent ●Systemic steroids: ○Not to be used in the routine care of psoriasis ○Role in the management of persistent, otherwise uncontrollable erythroderma that is causing metabolic complications ○Generalized pustular psoriasis of the Von Zumbusch type if other drugs are contraindicated or ineffective ○Steroids may occasionally be needed, and in high dosage to control hyperacute polyarthritis
  • 66. Others ●6-Thioguanine ●Tacrolimus and pimecrolimus ●Cytokines ●Protein kinase C inhibitor ●Zidovudine ●Somatostatin ●Liarazole ●Gluten free diet ●Photodynamic therapy
  • 67. Biologic Agents ●Biological's use should be restricted to: ○Patients with severe disease defined by a PASI score of 10 or more (or BSA of 10% or greater where PASI is not applicable) and DLQI of greater than 10 ○Patients who have failed to respond to, or who have a contraindication to, or who are intolerant to other systemic therapies such as cyclosporin and methotrexate
  • 68. Biologic Agents ●Biological agents licensed for treatment of psoriasis vulgaris ○Etanercept, a fully human soluble p75 TNF-Îą receptor fusion protein ○Infliximab, a chimeric human-immune antibody to TNF-Îą ○Adalimumab, a fully human recombinant antibody to TNF-Îą ○Ustekinumab, a fully human recombinant antibody to the p40 component of IL-12/IL-23 ○Alefacept, a fusion protein of lymphocyte function associated antigen-3 and IgG that inhibits T- cell activation ○Secukinumab, an anti-IL-17A monoclonal antibody
  • 69. Biologic Agents ●Infliximab is administered by IV infusion while the others are administered by SC injection ●Biological agent of choice ○For stable disease, particularly if not too severe (e.g., PASI >10 but <20) etanercept or adalimumab ○For patients requiring rapid disease control adalimumab or infliximab ○For patients with unstable or generalized pustular psoriasis severe nail disease infliximab ●Ustekinumab should be reserved for use as a second-line biological agent
  • 70. Future Therapies ●Therapies targeting Th17 pathway ●Briakinumab ●Ixekizumab ●Brodalumab ●Bimekizumab ●Netakimab ●Anti TNF therapy: Certolizumab pegol
  • 71. Future Therapies ●Janus kinase inhibitor: Tofacitinib ●IL-23 Inhibitors: ○Sonelokimab ○Mirikizumab ●Other molecules: ○Ponesimod ○Exenatide/liraglutide ○Deucravacitinib (tyrosine kinase 2 selective inhibitor) ○Piclidenoson (agonist of adenosine receptor)