Psoriasis and Lichen Planus

Question 1

Psoriasis epidemiology

Answer 1

• Varied world wide but roughly 2-4% of the population

- Bi-modal distribution: 20-30 yrs and 50-60 yrs

Question 2

Psoriasis genetics

Answer 2

• Important: 2-3 fold increase of monozygotic as opposed to dizygotic
• HLA:
  
  • Situated on short arm of chromosome 6
  • associated with corresponding MHC
  • HLA-Cw6 –> relative risk of 13, associated wth early onset
  • ‘Type 1 psoriasis’: early onset, family history, expression of HLA-Cw6
  • ‘Type 2 psoriasis’: late onset, no fhx, lack of Cw6
  • Other HLAs associated with different psoriasis –> HLA-B27 associated with sacroiliitis-associated psoriaiss and reactive arthritis
• Genome wide associations:
  
  • At least 9 psoriasis susceptibility regions - PSORS1-9
    
    • PSORS-1 meant to account for up to 50%,, is on chromosome 6p and contains genes like HLA-C and corneodesmosin
  • Have found there is a lot of association with inflammatory and immunologic pathways

Question 3

Psoriasis immunopathogenesis

Answer 3

• Dendritic cells
  
  • More DCs in skin in those with psoriasis
  • have enhanced ability to stimulate T cells
• T cells
  
  • CD-8 in epidermis and CD-4&8 in the dermis
  • demonstrated ++ infiltrate
• Neutrophils
  
  • not thought to be primary cause but usually recruited through cytokines
• Angiogenesis
  
  • From VEG-F
    Cytokines and chemokines
• Th1: interferon gamma and IL-2
• Obviously implication of IL-12 and IL-23
  
  • IL-23 stimulates Th17 to release IL-17 and IL-22 –> keratinocyte proliferation and dermal inflammation
• Levels of IL-22 correlates with disease severity (also thought subset of Th22 cells that contribute)
• IL-17 pdcing T cells may be more cytotoxic in nature
• Activated T cells and NK T cells in the epidermis results IFN-gamma to be released, activating STAT transcription factor family –> drives expression of large number of immune-related genes
• IFN-gamma pathway is a key feature of psoriasis –> vasodilation and T cell accumulation
• IL-1, IL-6 and TNF alpha also important
• Chemokines: CXCL8 (neutrophils), CCL17, CCL20, CCL27, CXCL9-11

Innate immunity and role of keratinocytes

• keratinocytes secrete anti-microbial peptides
• keratinocytes in psoriatic plaques express STAT3

Question 4

Psoriasis triggers

Answer 4

• External:
  
  • Koebnerisations ~25%–> generalized skin condition that can be triggered locally
  • other injury: sunburn, morbilliform drug eruption, viral exanthem
  • lag time 2-6 weeks
• Systemic
  
  • Infections –> strep, HIV
  • Endocrine: hypocalcaemia triggers generalised pustular, abnormal D3 levels, pregnancy
  • Psychogenic –> lag time up to 4 weeks
  • Medications: LIMBS: lithium, interferon, beta-blockers, anti-malarials, quick taper of steroids
  • Alcohol consumption
  • Smoking
  • Obesity

Question 5

Psoriasis hallmarks

Answer 5

• erythema –> elongated dilated capillaries
• thickening –> epidermal acanthosis and cellular infiltrates
• scale –> abnormal keratinization

Question 6

Psoriasis clinical

Answer 6

• Type 1 disease (HLA-Cw6+): earlier onset, more widespread, frequent recurrences
• Type 2: not so much
• Can be surrounded by a pale blanching ring: Woronoff’s ring
• Auspitz sign: removal of scale resulting in wet surface with pinpoint bleeding –> elongated vessels with thinning of the suprapapillary epidermis
• Pinpoint papules surrounding existing plaques indicate that the patient is in an unstable phase of the disease
• Expanding lesion: active edge with more intense erythema
• Involution usually starts in the centre, resulting in the annular lesions

Question 7

Chronic plaque psoriasis clinical

Answer 7

• Symmetric, sharply defined plaques
• scalp, elbows, knees, lumbosacral area, hands, feet
• 45%: genitals

Question 8

Guttate psoriasis clinical

Answer 8

• More common in children and adolescents
• Frequently preceded by URTI
• Over half of patients have an elevated ASOT, anti-DNAase or streptozyme titre

Question 9

Erythrodermic psoriasis clinical

Answer 9

• Generalized erythema and scaling

- Clues: previous plaques in classic locations, nail changes, facial sparing

Question 10

Generalized pustular psoriasis triggers

Answer 10

• Pregnancy: impetigo herpetiformis
• Rapid tapering of steroids
• Hypocalcaemia
• Infections
• Localized topical irritants

Question 11

Four patterns of generalized pustular psoriasis

Answer 11

• Von Zumbusch: abrupt generalized erythema and pustulation, painful skin, fever, general malaise. After a few days, pustules resolve –> extensive scaling
• Annular pattern: annular, with erythema and scaling with pustulation at the advancing edge. Enlarge centrifugally over hours to days, and central healing
• Exanthematic: acute eruption of small pustules, abruptly appearing and disappearing over a few days. Often following infection, or medications such as lithium. No systemic symptoms. Overlap of this with AGEP
• Localized: sometimes pustules appear within or at the edge of existing psoriatic plaques, and this can be seen during unstable CPP and following the application of irritants such as tar and anthralin

Question 12

Autoinflammatory disorders that look like generalized pustular psoriasis

Answer 12

Clinical presentation of several inherited autoinflammatory disorders resembles generalized pustular psoriasis: CARD14, DIRA, DITRA, ADAM17 deletion

Question 13

Pustulosis of the palms and soles

Answer 13

• sterile pustules of palmoplantar surfaces with yellow-brown macules, can also get scaly erythematous plaques
• minority of patients have CPP elsewhere
• remain localized tot he palms and soles, and is chronic
• triggers: focal infections, stress
• Can also be part of an entity such as SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis)

Question 14

Acrodermatitis continua of Hallopeau

Answer 14

• Rare manifestation
• Pustules in the distal portion of fingers and sometimes toes
• Pustules then often followed by scaling and crust formation
• May also be beneath the nail plate on the nail bed, and can get shedding of nail plates
• Transition into other forms of psoriasis can occur
• May be accompanied by annulus migrans of the tongue

Question 15

Scalp psoriasis

Answer 15

• can get seb derm and psoriasis here
• can advance onto periphery of the face, retroauricular and posterior upper neck
• asbestos like appearance - can adhere to hair shafts in clumps: pityriasis amiantacea (pic below) - can see in seb derm, secondarily infected atopic dermaitis and tinea capitis, but psoriasis is the most common cause
• alopecia can develop, particularly in TNF inhibitor induced psoriasis

Question 16

Causes of pityriasis amiiantacea

Answer 16

Psoriasis, seb derm, tinea capitis, infected eczema

Question 17

Flexural psoriasis

Answer 17

• Shiny, pink-red sharply demarcated thin plaques
• Much less scale
• central fissure often seen
• Most common sites: retroauricular fold, intergluteal cleft, inguinal crease, axillae and inframammary region
• Localized dermatophyte, candida or bacterial infections can trigger flexural psoraisis

Question 18

Oral psoriasis

Answer 18

• Annulus migrans: annular erythematous lesions with white scale –> acrodermatitis of Hallopeau and generalized pustular psoriasis –> most commonly on tongue, and histologically similar to geographic tongue (see pic)
• occasionally can be on buccal mucosa

Question 19

Nail psoriasis clinical

Answer 19

• Affects the nail matrix, bed and hyponychium
• Pits: small parakeratotic foci in the proximal portion of the nail matrix
• Leukonychia and loss of transparency (less common): involvement of the midportion of the nail matrix
• Whitish, crumby, poorly adherent nail: entire nail matrix is involved
• Oil drop of salmon patch: exocytosis of leukocytes beneath the nail plate
• Splinter haemorrhage: increased capillary fragility
• Subungual hyperkeratosis and distal onycholysis: due to parakeratosis of the distal nail bed
• When remove subungual debris can be an exacerbating factor

Question 20

Risk factors for PsA

Answer 20

• initial presentation at early age
• female gender
• polyarticular involvement
• genetic predisposition
• radiographic signs of the disease early on
  Nail involvement strong predictor of concomitant psA

Question 21

Hallmark of PsA

Answer 21

Hallmark: erosive change radiographically –> can occur years after the presenting peri-articular inflammation

Question 22

PsA also get inflammation of what else

Answer 22

• tendonitis
• enthesitis
• dactylitis

Question 23

5 subtypes of PsA

Answer 23

• Mono and asymmetric oligoarthritis
  
  • most common
  • inflammation of the DIP and PIP joints of the hands and feet
  • DIP and PIP on same digit: ‘sausage’ digit
  • Unusual to involve MCP joint
  • may be accompanied by involvement of larger joints
• Arthritis of the DIP joints
  
  • may become fixed in flexed position
• RA- like
  
  • Symmetric polyarthritis - involves small and medium-sized joints, in particular the PIP, MCP, wrist, ankle and elbow
  • most patients are seronegative for RF
• Arthritis mutilans
  
  • least common type
  • severe, rapid progressive joint inflammation resulting in destruction of the joints and permanent deformity
  • digits become shorter, wider and softer to palpate because of osteolysis and telescoping phenomenon
• Spondylitis and sacroiliitis
  
  • axial arthritis, involvement of knees and sacroiliac joints
  • often HLA-B27 positive, and may have associated IBD and/or uveitis

Question 24

ILVEN

Answer 24

• linear psoriasiform lesions that follow the lines of Blaschko
• chronic and resistant to tehrapy

Question 25

Reactive arthritis

Answer 25

• Features:
  
  • Urethritis - often from chlamydia trachomatis
  • Arthritis - polyarthritis and sacroilitis
  • Ocular - conjunctivitis, iritis, uveitis with glaucoma, keratitis
  • Oral ulcers
  • Psoriasiform skin lesions - only 5% of reactive arthritis patients –> soles, extensor surfaces, penis, dorsal aspects of the hands, fingers, nails and scalp
    
    • Keratoderma blennorrhagicum: plantar surface has thick, yellow scale
    • Balanitis circinata: psoriatic plaques on the penis
• Strong association with HLA-B27
• Self-limiting, lasting weeks-months
• HIV infected patients can also develop this disorder, and it may be more severe

Question 26

Sneddon-Wilkinson

Answer 26

• Clinical:
  
  • flexural annular or polycyclic lesions
  • superficial, subcorneal pustules
  • gravity-induced demarcation in some vesiculopustules, with clear fluid superiorly and pus inferiorly
  • has a cyclic course –> as the pustules resolve, they are replaced by superficial scaling and then new pustules form again
  • Rarely associated IgA paraproteinaemia
• Need IF to distinguish from IgA pemphigus
• Can treat with dapsone

Question 27

Psoriasis and associations with other diseases

Answer 27

Skin diseases

• atopy lower
• increased risk of lichen simplex chronicus
• Seborrhoeic dermatitis

Infections

• rarely infected –> increased production of anti-microbial peptides
• Onychomycosis
• Candida in flexural psoriasis

Cancer

• higher incidence rate of all malignancies
• > 200 PUVA treatments –> increased risk, particularly SCC

Internal diseases

• cardiovascular: MI, PAD, cerebrovascular accidents
• Metabolic syndrome –> elevated CRP risk factor for cardiovascular disease
• TNF-alpha and IL-6 can target adipocytes and induce dyslipidaemia
• Non-alcoholic steatohepatitis
• IBD - Crohns and UC –> HLA-B27 positive

Question 28

Psoriasis histology of active lesion

Answer 28

• Epidermis:
  
  • acanthosis
  • focal accumulations of neutrophils and lymphocytes
  • variable spongiosis
  • absent granular layer
  • parakeratosis
  • Spongiform pustule of Kogoj: neutrophils within a spongiotic pustule
  • Microabscess of Munro: accumulation of neutrophil remnants in the stratum corneum
• Dermis:
  
  • capillaries are increased in number and length, tortuous
  • oedema, particularly at the tops of the papillae
  • mixed perivascular infiltrate of lymphocytes, macrophages and neutrophils

Question 29

Psoriasis histology of stable lesion

Answer 29

• Epidermis:
  
  • Hyperproliferation
  • Elongated rete ridges, squared off
  • bases of some rete ridges coalesce
  • horny layer has parakeratotic foci, with an absence of stratum granulosum
  • Micropustules and abscesses may be seen
• Dermis
  
  • capillaries elongated and tortuous, extending up into the dermal papillary
  • thinning of suprapapillary plate
  • perivascular infiltrate of lymphocytes and macrophages

Question 30

Pustular psoriasis histology

Answer 30

• Neutrophils accumulate between eosinophilic strands of keratinocytes
• large collections of neutrophils in stratum corneum, surrounded by parakeratosis
• Hallmarks: Kogoj and Munro

Question 31

Topical treatment for psoriasis - steroids and vit D

Answer 31

Steroids

• Contraindications:
  
  • Infections
  • Skin atrophy
  • ACD due to steroids
  • Pregnancy or lactation
• No efficacy data available for prolonged treatment
• Tachyphylaxis can occur quite quickly –> need intermittent treatment schedules

Vitamin D3 analogues

• Vitamin D3 inhibits epidermal proliferation: induces normal differentiation by enhancing cornified envelope formation and activating transglutaminase
• also inhibits neutrophil function
• when calcipotriene used in conjunction with diprosone is used –> 70% reduction in PASI has been observed

Question 32

Topical anthralin

Answer 32

• Anti-hyperproliferative
• Inhibits mitogen-induced T-lymphocyte prolfieration and neutrophil chemotaxis
• second-line treatment for mild-mod or severe psoriasis
• contraindicated:
  
  • pustular psoriasis
  • erythrodermic psoriasis
  • unstable plaque psoriasis in a phase of progression

Question 33

Topical retinoids for psoriasis

Answer 33

• Tazarotene:
  
  • selectively binds RAR-beta and RAR-gamma
  • decreased epidermal proliferation and inhibits psoriasis-associated differentiation
• usually second line
• irritation of skin, burning, pruritus, limits use
• maximal area that can be treated is 10-20% BSA
• safety data up to 1 year is available for treatment
• CI: unstable, erythrodermic, ACD, pregnancy/lactation

Question 34

Tar, sal acid and calcineurin inhibitors for psoriasis

Answer 34

Salicylic acid

• 5-10% as keratolytic effect
• for scalp: oil or ointment base
• need to be careful of systemic intoxication, particularly in infants with reduced renal function

Coal tar

• range of anti-inflammatory
• antipruritic
• mutagenic potential, so don’t use in pregnant or lactating women

Calcineurin inhibitors

• treat facial and flexural psoriasis
• RCTs support its use