‫بسم هللا الرحمن الرحيم‬

‫‪1‬‬
Papulosquamous Dermatoses

Rania AlSaied
MD

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Pityriasis Rubra Pilaris

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 It is a chronic papulosquamous disorder
of unknown etiology characterized by
reddish orange scaly plaques,
palmoplantar keratoderma, and
keratotic follicular papules. The disease
may progress to erythroderma with
distinct areas of uninvolved skin, the so-
called islands of sparing.
4
 Griffiths divided PRP into 5 categories:
classic adult type, atypical adult type,
classic juvenile type, circumscribed
juvenile type, and atypical juvenile type.
More recently, an HIV-associated type
has been added to this classification
system.

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Pathophysiology

 The etiology is unknown. A familial form

of the disease exists, with an autosomal
dominant inheritance pattern; however,
most cases are sporadic. One
hypothesis is that PRP may be related
to an abnormal immune response to an
antigenic trigger. Case reports have
described PRP occurring after
streptococcal infections.
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Mortality/Morbidity

 Patients with PRP can have painful and

disabling palmoplantar keratoderma.
Nail dystrophy and shedding may be
present. However, most of the
morbidity associated with PRP is
associated with the erythroderma

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Sex
, Age
 PRP occurs equally among men and women
 The familial form of PRP typically begins in
early childhood and has an autosomal
dominant inheritance pattern.
 The acquired form of PRP has a bimodal age
distribution, with peaks in the first and fifth
decades of life, but it can begin at any age.

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History
 The familial form of PRP has a gradual onset,
whereas the acquired form has an acute onset.
 The disease typically spreads in a craniocaudal
direction.
 Patients first notice redness and scales on the face
and the scalp.
 This is often followed by redness and thickening of
the palms and the soles
 The lesions may expand and coalesce to cover the
entire body.

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Physical

 Skin
 PRP is characterized by orange-red or
salmon-colored scaly plaques with sharp
borders, which may expand to involve the
entire body
 Often, areas of uninvolved skin, referred to as
islands of sparing, are present.
 Follicular hyperkeratosis is commonly seen on
the dorsal aspects of the proximal phalanges,
the elbows, and the wrists

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 Palmoplantar keratoderma occurs in
most patients and tends to have an
orange hue. Painful fissures may
develop in patients with palmoplantar
keratoderma.
 Pruritus, although not a major
symptom, may occur in the early stages
of the disease.
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 Nails
 Nail changes include distal yellow-
brown discoloration, subungual
hyperkeratosis, longitudinal ridging, nail
plate thickening, and splinter
hemorrhages.
 Nail pitting is not typical.

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Histologic Findings
 Histologic features are not pathognomonic, but they
are useful to rule out other possible papulosquamous
and erythrodermic disorders. Features on light
microscopy include hyperkeratosis with alternating
orthokeratosis and parakeratosis forming a
checkerboard pattern in the stratum corneum, focal
or confluent hypergranulosis, follicular plugging with
perifollicular parakeratosis forming a shoulder effect,
thick suprapapillary plates, broad rete ridges, narrow
dermal papillae, and sparse superficial dermal
lymphocytic perivascular infiltration

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 Medical Care
 Topical medications
 Topical corticosteroids may provide some patient
comfort, but they are believed to have little long-
term therapeutic effect.
 Emollients reduce fissuring and dryness,
providing some patient comfort. Petroleum
jelly or one of the many proprietary
emollients may be used.

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Systemic therapy
More severe cases may require:
 Systemic retinoids

 Immunosuppressants like

Azathioprine
Methotrexate
Cyclosporin

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Complications
 PRP can cause painful and disabling
palmoplantar keratoderma.
 Nail dystrophy and shedding may occur.
 Erythroderma is a reaction pattern of the skin
that can occur in the setting of several
different skin disorders, most commonly
including psoriasis, eczema, lymphoma, drug
reactions, and PRP. It is characterized by
generalized erythema and scales, hair loss,
and onycholysis.
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Prognosis
 Each type of PRP has its own prognosis.
In general, the familial form of the
disease may be persistent throughout
life, and the acquired form of the
disease may resolve spontaneously
within 1-3 years.

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Pityriasis Rosea

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Background
 Pityriasis rosea (PR) is a common
benign papulosquamous disease
 . Pityriasis denotes fine scales, and
rosea translates as rose colored or pink.
 PR can have a number of clinical
variations. Its diagnosis is important
because it may resemble secondary
syphilis.

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Pathophysiology
 PR has often been considered to be a viral
exanthem. Its clinical presentation supports
this concept. PR has been linked to upper
respiratory infections, it can cluster within
families and close contacts, and it has an
increased incidence in individuals who are
immunocompromised. As with viral
exanthems, the incidence may increase in the
fall and the spring.

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 recent work demonstrated human
herpesvirus (HHV)–7 viral DNA in both
the lesions and the plasma in patients
with PR.

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 Sex
PR is more common in women than in men.
One study found it to be twice as common in
women as in men.
 Age

PR commonly develops in children and young

adults, although any age group can be
affected. Most patients are aged 10-35 years.

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History
 The history should include questions
about close contacts with similar
eruptions. This finding is uncommon
because most cases of PR are sporadic,
as PR is thought to reflect a weakly
contagious disease. A history of
medication intake should be obtained
because several medications have been
shown to cause a similar exanthem.
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 The disease typically begins with a
solitary macule that heralds the
eruption (called the herald spot/patch),
which is usually a salmon-colored
macule. This initial lesion enlarges over
a few days to become a patch with a
collarette of fine scale just inside the
well-demarcated border.
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 Within the next 1-2 weeks, a generalized exanthem
usually appears, although it may occur from hours to
months after the herald patch. This secondary phase
consists of bilateral and symmetric macules with a
collarette scale oriented with their long axes along
cleavage lines. This phase tends to resolve over the
next 6 weeks, but variability is common.
 Pruritus is common, usually of mild-to-moderate
severity, and it occurs in 75% of patients.

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Physical
 The herald patch is usually a single pink
patch, 2-10 cm in diameter, on the neck
or the trunk with a fine collarette scale.
It is observed in more than 50% of
patients, and it may occur as multiple
lesions or in atypical locations.

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 About 1-2 weeks after the herald patch is seen, the
generalized eruption appears, although it has been
known to occur from hours to 3 months later. It
consists of salmon-colored macules or patches, 0.5-
1.5 cm in diameter, with a collarette scale, often
described as having a cigarette paper–like
appearance. The long axes of the lesions are oriented
in a parallel fashion along cleavage lines, giving the
classic Christmas tree pattern.
 These secondary lesions most commonly occur on the
trunk, the abdomen, the back, and the proximal upper
extremities.

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D.D
 Lichen Planus
Nummular Dermatitis
Psoriasis, Guttate
Seborrheic Dermatitis
Syphilis
Tinea Corporis
Drug induced PR like eruptions:
captopril, levamisole, omeprazole, Barbiturates,
aspirin, ketokonazole

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Lab studies
 One must be careful to rule out syphilis.
 A screening rapid plasma reagin (RPR)
test or a VDRL test should be ordered
for appropriate individuals.

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Histopathology
 It shows superficial perivascular dermatitis
 Focal parakeratosis in mounds, hyperplasia, and
focal spongiosis are observed in the epidermis.
 The epidermis may show exocytosis of lymphocytes,
variable spongiosis, mild acanthosis, and a thinned
granular layer.
 In the dermis, extravasated red blood cells are a
helpful finding along with a perivascular infiltrate of
lymphocytes, histiocytes, and eosinophils. A number
of monocytes are also commonly present.

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35
Treatment
 Emollients
 Antihistamines ( if there is pruritus)
 UVB phototherapy ( for persistent PR)

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Complications
 The main morbidity is from pigmentary
changes, which are possible with the
healing lesions.
 Both postinflammatory
hyperpigmentation and
hypopigmentation may occur.

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Prognosis
 The prognosis for PR is excellent.
Patients may return to work or school
because they are not considered to be
contagious.

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Psoriasis

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Objectives
 Identify the pathogenic factors for
development of psoriasis
 List the clinical features of psoriasis
 Describe the progressive management
of the clinical features of psoriasis
 List the adverse effects of psoriatic
treatments

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Psoriasis
 Chronic skin disorder; "itch" =
psora
 Incidence

 Other derm conditions

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Psoriasis
 T-cell mediated inflammatory dz
 Epidermal hyperproliferation 2O to
activation of immune system
 Altered maturation of skin
 Inflammation
 Vascular changes

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44
 Background
 Epidemiology
 Age

 Genetic

 Scandinavian/European descent

 Risk Factors

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 Psoriasis, an inherited disease
If you have psoriasis, what is the risk to:
 Your unrelated neighbor? About 2%
 Your sibling? 15-20%
 Your identical twin? 65-70%
 Your child? 25%

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N P Disorganized
O STRATUM S
R
CORNEUM O Neutrophil
M STRATUM R accumulation
GRANULOSUM
A I
L STRATUM
A
SPINOSUM S Immaturity
I
S Proliferation

STRATUM
BASALE
DERMIS
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48
Psoriasis: Associated Factors
 Genetic Factors:
- 30% of people with psoriasis have had
psoriasis in family
- Autosomal dominant inheritance
 Nongenetic Factors:
- Mechanical, ultraviolet, chemical injury
- Infections: Strep, viral, HIV
- Prescription Drugs, stress, endocrine,
hormonal, obesity, alcohol, smoking

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 Clinical Presentation
 Erythematous, raised plaques with
silvery scales
 Symmetric
 Pruritic/ Painful
 Pitting Nails
 Arthritis in 10-20% of patients
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51
 Psoriasis: Clinical
Presentation
Type Characteristics
Plaque psoriasis Dry scaling patches (AKA common psoriasis) 75%
Guttate psoriasis Drop-like dots, occurs after strep or viral infection 12%
Erythrodermic Exfoliation of fine scales (total body “dandruff”),
psoriasis widespread, often accompanied by severe itching and
pain 7%
Pustular Pus-like blisters, noninfectious, fluid contains white blood
psoriasis cells 2%
Nail psoriasis Seen on toenails and fingernails, starts as numerous pits,
at times progresses to yellowing, crumbly, and thickened
nail; nails may slough
Palmar/Plantar Erythema, thickening and peeling of the skin, blistering is
psoriasis often present. Can lead to disability.
Psoriatic arthritis Inflammation, swelling, and joint destruction
Scalp psoriasis Plaque-type lesion
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Psoriatic Plaque

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Chronic Plaque Psoriasis

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Erythrodermic Psoriasis

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Nail changes

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Guttate Psoriasis

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 Nail Changes
 In 78% of psoriatic patients
 Fingernails>Toenails
 Four changes
1. Onycholysis (= separation from nail bed)
2. Pitting*
3. Subungual debris accumulation
4. Color alterations
*Pitting rules out a fungal infection
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59
 Psoriatic Arthritis
 In 10-20% of psoriasis patients
 Peripheral interphalangeal joints

 No elevated serum levels of

rheumatoid factors (as seen in

rheumatoid arthritis, yet has all other
features)
 Often seen in patients with nail and

scalp psoriasis 60
 OLA Photonumeric Guidelines
(overall lesion assessment)

0 = none 1 = minimal 2 = mild

3 = moderate 4 = severe 5 = very severe

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62
 The Majority of Moderate-Severe Psoriasis Patients
Are Under-Treated

 50% of patients with moderate or

worse disease are currently
untreated1
 46% have topical therapy only
 Reason dermatologists Topicals
Other only
do not use more therapies
aggressive therapies2 46%
54%
 Safety concerns
 Time consuming
 Cost

1
Leonardi, 2003; 2 Market Measures/Cozint LLP, June 2003.
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Psoriasis: Treatment
 Lubrication
 Removal of scales
 Slow down lesion proliferation
 Pruritus management
 Prevent complications
 Lessen patient stress
 Season and climate
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 S te p 1

CoalTar T o p i c a l S t e r o id

A n t h r a l in C a lc ip o t r ie n e T a z a ro te n e I n t r a l e s i o n a l S t e r o id

Supplementary C lim a t o t h e r a p y M o is t u r iz e r s K e r a t o ly t ic s
Tx
Step 2
P U V A +
PUVA S te p 1 a g e n t

Step 3
R o t a t i o n a l:
M e th o tre x a te C y c lo s p o r in e 1 2 -2 4 m o n th s
A c it r e t in o f e ach
s te p 3 a g e n t

Step 4
Enbrel/Remicade/Amevive/Raptiva 65
 Emollients and Moisturizers
 Moisturizes, lubricates and soothes dry and
flaky skin.
 Produces occlusive film to limit water
evaporation from skin. Increased hydration
allows stratum corneum to swell- scaling
decreases, skin is more pliable.
 Adverse Effect: contact dermatitis, folliculitis
(rare)
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 Keratolytics = “SKIN LIFTERS”
 Helps remove scales and reduce
hyperkeratosis
 Salicylic Acid 2-6%
 Enhance absorption of other drugs
 AE: N/V, tinnitus, hyperventilation (rare
=salicylism)

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Tars
 Coal Tar – made from crude coal
 Decreases epidermal cell mitosis and
scale development
 Reduces sebum production
 Anti-inflammatory effects
 5% coal tar concentration most
effective (1%-6%)

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Coal Tar
 Problems with coal tar:
 Smell

 Sting

 Stain

 Sensitize

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 Coal Tar
 Very useful in guttate psoriasis and for scalp
psoriasis as a shampoo
 Not recommended as 1st line tx:
 Erythrodermic & Pustular
 Irritation may lead to Koebner’s phenomenon
 Use only on lesions that are well separated,
not too big
 Phototoxic response sunburn may become
erythematous 70
 Corticosteroids
 Reduce inflammation, itching and scaling
 Anti-inflammatory effect
 Decrease in vascular permeability,

decreasing dermal edema and leukocyte

penetration into skin
 Antiproliferative effect
 Immunosuppressive effect

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 Corticosteroids
Level of Potency Corticosteroid Commercial Products

Ultra-high Halobetasol propionate Ultravate crm/oint

Clobetasol propionate Temovate crm/oint
Betamethasone dipropionate Diprolene oint
Diflorasone diacetate Psorcon oint

High Halcinonide Halog crm

Amcinonide Cylocort oint
Betamethasone dipropionate Diprolene AF crm
Mometasone furoate Elocon oint
Diflorasone diacetate Florone oint
Fluocinonide Lidex crm,gel,oint
Desoximetasone Topicort crm,oint,gel

Mild to high Halcinonide Halog oint,crm,soln

Triamcinolone acetonide Aristocort A oint
Betamethasone dipropionate Diprosone crm
Fluocinonide Lidex-E crm 72
 Corticosteroids
Level of Potency Corticosteroid Commercial Products

Mild Hydrocortisone valerate Westcort

Triamcinolone acetonide Kenalog crm and oint
Flurandrenolide Cordran oint
Mometasone furoate Elocon crm
Fluocinolone acetonide Synalar oint
Low to mild Hydrocortisone valerate Westcort crm
Triamcinolone acetonide Kenalog crm and oint
Flurandrenolide Cordran crm
Betamethasone dipropionate Diprosone lotion
Hydrocortisone butyrate Locoid crm
Flucolone acetonide Synalar crm
Low Alclometasone dipropionate Aclovate crm and oint
Betamethasone valerate Valisone lotion
Fluocinolone acetonide Synalar soln and crm
Hydrocortisone, dexamethasone,
prednisolone, methylprednisolone
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Corticosteroids
 Ointments: helps hydrate; good for dry,
hyperkeratotic, scaly lesions
 Cream: for use on all areas, useful for
infected lesions
 Solutions: for scalp psoriasis, often
contain alcohols which can be painful
with open lesions

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Corticosteroids
 Adverse Effects: (esp. with occlusion)
 Systemic absorption
 Dermal atrophy
 Telangiectasis
 Ecchymoses
 Peri-orbital acne
 Poor wound healing
 Pyogenic infections

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Vitamin D3
 Isolated from cod liver oil in 1936
 Made in human skin through reaction:
7-dehydrocholesterol & UV light
 Calcitriol’s properties in psoriasis:
1. Increase cellular differentiation
2. Inhibits cellular proliferation

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Vitamin D3
 Adverse Effects:
 Hypercalcemia
 Hypercalciuria
 Mild calcitriol intoxication: renal stones
 Not for long term use, therefore analogues
were developed

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 Vitamin D3 Analogue

 Calcipotriene (Dovonex®)
 Indication = Moderate plaque psoriasis
 Reduces scaling and thickness of plaque, but not
the erythema; what would you use in combo?
 Max weekly cumulative dose: 5mg
= 100gm of 50 mcg/gm or 2 tubes
 Applied BID x 8 weeks

78
 Vitamin D3 Analogues

 Calcipotriene (Dovonex®)
 Not for pustular or erythrodermic psoriasis due to
increased systemic absorption
 AE: irritation, hypercalcemia (when applied in large
amounts)
 CI in pregnancy, lactation, children

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Retinoids
 Vitamin A derivatives

 MOA:
1. Normalization of abnormal

keratinocyte differentiation
2. Reduction in keratinocyte

proliferation
3. Reduction in inflammation

80
 Oral Retinoids
 Etretinate & Acitretin (Soriatane®)
 Second generation retinoids
 For pustular and erythrodermic psoriasis
 Etretinate withdrawn from US market- 1998
 Acitretin= active metabolite of etretinate
 Reserved for treatment of severe forms of
psoriasis due to side effects.

81
 Soriatane : Dosage
 Usual dose: 25-50mg/day as single
dose
 Dosage form: 10mg, 25mg capsules

82
 Soriatane : Precautions
 Avoid in severe liver and kidney dz
 Avoid in patients with h/o alcohol dz
 ETOH = reverse metab to etretinate
 Teratogenic- CI in pregnancy
 Contraception one month before treatment and
at least 3 years after
 Monitor: serum lipids, LFTs, serum creatinine
(problematic as alternatives have similar
limitations)

83
Soriatane : Adverse Effects
 Peeling, drying skin
 Diffuse alopecia
 Nail changes
 Sticky, clammy skin
 Muscle pain
 Calcification of ligaments
84
 Soriatane
33% of patients had an elevation of AST (SGOT),
Hepatotoxicity ALT (SGPT) or LDH
Black Box Warning

Alopecia 50-75% of patients

50-75% skin peeling

Mucocutaneous 25-50% dry skin
25-50% pruritus
23% dry eyes

66% increase in triglycerides

Lipid
33% increase in cholesterol
Metabolism
40% reduction in HDL

85
 Topical Retinoids

 Tazarotene (Tazorac®)
 Third generation retinoid

 Stable plaque psoriasis (up to 20% of

body surface area involvement)

 Severe facial psoriasis

 Water based emollient gel or cream

86
 Tazarotene (Tazorac®)

 Apply once daily x12 weeks

 AE: pruritus, burning, erythema
 ? More selective retinoid than
Soriatane resulting in fewer ADRs
 Oral formulation pending at FDA

87
 Counseling points
 Apply a moisturizer to the skin before using the Tazorac; it
can dry out the skin.

 Apply it once per day about 30 minutes before bedtime.

 Rub about a pea-sized amount only into each lesion; it can

irritate normal skin.

 If it spreads to the unaffected skin, wash it off with water.

Zinc oxide can protect the skin

 Apply sunscreen
88
 Methotrexate
 For moderate-severe psoriasis non-responsive
to topical treatment
 MOA:
 binds to DHFR which leads to reduction of
tetrahydrofolate, which inhibits pyrimidine
synthesis. Pyrimidine is needed for formation of
DNA base pairs, therefore decrease in DNA
replication esp rapidly dividing cells as in skin
 Induces apoptosis of activated T cells
89
 FOLIC ACID

METHOTREXATE
90
Response to Methotrexate
 Suppression of B cells and macrophages
 Induces T-cell apoptosis
 Suppresses IL-1 and IL-8 production by
peripheral blood mononuclear cells
 Reduces T cell production of interferon-
gamma and TNF

91
 Methotrexate: Precautions
 Contraindicated:
 Pregnancy, lactating mothers

 Renal & liver problems

 Preexisting severe anemia,

leukopenia, thrombocytopenia
 Alcoholics

 Active infectious disease

92
 Methotrexate: Dosage
 Initial: 2.5-5mg q12h x3 doses qweek
 Titrate up weekly by 2.5mg increments [if
blood counts (weekly then monthly) and
LFTs (q4 month)allow] until symptoms
respond
 Injections: IM or SQ
 Max: 50mg/week, but some 75mg/week

93
Methotrexate: Adverse Effects
 Headache, chills, fever, fatigue, abdominal
pain, nausea, vomiting, dizziness
 Pruritus, alopecia, urticaria, ecchymosis,
sunburn (phototoxicity)
 Osteopathy- rare & at low doses
 Pulmonary fibrosis- CXR yearly
 Obtain liver biopsy after each 1.5gm
 Folate rx on days NOT taking MTX

94
 Cyclosporine

 For psoriatic lesions resistant to other

therapies
 MOA: prevention of IL-2 transcription,
prevention of primary T-cell activation
and reduction of T cell cytokines.

95
 Cyclosporine: Dosage
 Oral Cyclosporine Microemulsion: Neoral
 Capsules, solution
 Initial: 2.5 mg/kg/day split BID x4 wks
 May increase dose at 2 week intervals of
~0.5 mg/kg/day increments
 Max: 5 mg/kg/day
 Relapse:
 6 weeks (50%)-16 weeks (75%)
96
 Cyclosporine:Adverse Effects
 Headaches, paresthesias, flu-like symptoms,
abdominal pain, nausea.
 Hypertension
 Nephrotoxicity:acute  blood flow; chronic form
 dose and duration
 Neurotoxicity
 Hepatoxicity
 Hyperglycemia
 Should be used as short term therapy (<1 year)
to avoid further adverse effects (gingival
hyperplasia, hyperlipidemia, hirsutism, etc). 97
Phototherapy
 Used over 100 years for moderate-
severe psoriasis
 UVA (315-400 nm), UVB (290-315 nm)

 313 nm = most effective wavelength for

psoriasis

98
Phototherapy
 Ultraviolet B
 Relatively non-toxic
 Can be used as a single-agent
 Usually combined with lubricants
 Ingram’s regimen (Anthralin)
 Goeckerman’s regimen (Tar)

99
Phototherapy

100
Phototherapy

101
Phototherapy

102
Phototherapy

103
 PUVA
 PUVA= Psoralen + Ultraviolet A
 Theories of MOA:
1. Psoralen intercalates into DNA, inhibiting DNA
replication and thus, inhibiting epidermal cell
hyperproliferation
2. Free radical formation damages cell
membrane, cytoplasmic contents and nucleus
of epidermal cells…inhibiting growth of cells.
3. Increased apoptosis of activated T-cells
104
 Oral PUVA

 Psoralen = “P” in PUVA = a photosensitizer

 Methoxsalen (Oxsoralen-Ultra, 8-MOP)
 10 mg capsules
 Given 2 hours before UVA irradiation
 Symptomatic control of severe, recalcitrant
disabling psoriasis, not responsive to other
therapy after biopsy confirmed diagnosis
105
PUVA
 Phototoxicity
 Related to quantity of psoralen and amount of
UVA applied
 Reaction peaks 48-72hrs after treatment
 Erythema, blistering, edema
 Administer 2-4x/ week
 Tanning occurs, so gradually increase dose
of UVA
 ~20 sessions over 4-8 weeks clears lesions

106
Oral PUVA: Adverse Effects
 Constipation, diarrhea, nausea,
vomiting, pruritus, delayed-onset
erythema
 Oral psoralens distribute to entire
body and eyes: protect eyes and skin
from sunlight 6 hours after treatment
 Long-term: premature aging,
cataracts, skin cancer (rare)

107
First Generation Biologicals
 Infliximab & Etanercept:
immunomodulators
 used initially for rheumatoid arthritis;
work against TNF-alpha

108
 TNF Inhibitors
 Both Remicade and Enbrel are quite effective
(>75% of psoriatics respond) even if only
skin is affected
 Enbrel SQ once* or twice weekly; Remicade
IV
0, 2 and 6 weeks
 Concerns: exacerbate MS and TB, induce
SLE and CHF, palliative not curative

109
 New Therapies
 Alefacept (Amevive)
 Inhibits CD45RO+

memory effector T
lymphocytes, by binding
to their CD2 receptor also
leads to apoptosis
 Administered IV or IM

qweek x12 wks

 AE: dizziness, chill,

nausea, cough
110