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1 Papulosquamous Dermatoses
Rania AlSaied MD
2 Pityriasis Rubra Pilaris
3 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.
5 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.
6 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
7 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.
8 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.
9 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
10 11 12 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.
13 Nails Nail changes include distal yellow- brown discoloration, subungual hyperkeratosis, longitudinal ridging, nail plate thickening, and splinter hemorrhages. Nail pitting is not typical.
14 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
15 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.
16 Systemic therapy
More severe cases may require: Systemic retinoids Immunosuppressants like Azathioprine Methotrexate Cyclosporin
17 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.
18 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.
20 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.
21 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.
22 recent work demonstrated human herpesvirus (HHV)ƛ7 viral DNA in both the lesions and the plasma in patients with PR.
23 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.
24 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.
25 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.
26 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.
27 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.
28 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 paperƛlike 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.
29 30 31 D.D
Lichen Planus Nummular Dermatitis Psoriasis, Guttate Seborrheic Dermatitis Syphilis Tinea Corporis Drug induced PR like eruptions: captopril, levamisole, omeprazole, Barbiturates, aspirin, ketokonazole
32 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.
33 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.
34 35 Treatment
Emollients Antihistamines ( if there is pruritus) UVB phototherapy ( for persistent PR)
36 Complications
The main morbidity is from pigmentary changes, which are possible with the healing lesions. Both postinflammatory hyperpigmentation and hypopigmentation may occur.
37 Prognosis
The prognosis for PR is excellent. Patients may return to work or school because they are not considered to be contagious.
38 Psoriasis
39 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
40 Psoriasis
Chronic skin disorder; "itch" = psora
Incidence
Other derm conditions
41 Psoriasis
T-cell mediated inflammatory dz Epidermal hyperproliferation 2O to activation of immune system Altered maturation of skin Inflammation Vascular changes
42 43 44 Background
Epidemiology Age Genetic Scandinavian/European descent Risk Factors
45 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%
46 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 47 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
49 Clinical Presentation
Erythematous, raised plaques with silvery scales Symmetric Pruritic/ Painful Pitting Nails Arthritis in 10-20% of patients
50 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 ³dandruff´), 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 52
Psoriatic Plaque
53 Chronic Plaque Psoriasis
54 Erythrodermic Psoriasis
55 Nail changes
56 Guttate Psoriasis
57 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 58 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 severe61 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 Topicals Reason dermatologists Other only therapies do not use more 46% 54% aggressive therapies2 Safety concerns Time consuming Cost 1 Leonardi, 20033;; 2 Market Measures/Cozint LLP, June 20033.. 63 Psoriasis: Treatment
Lubrication Removal of scales Slow down lesion proliferation Pruritus management Prevent complications Lessen patient stress Season and climate
64 St
Coal Tar Topical Steroid
Ant ralin Calcipotriene Tazarotene Intralesional Steroid
Supplementary Climatot erapy Moisturizers Keratolytics Tx Step 2
PUV A + PUVA S t e p 1 a g e n t
Step 3 Rotational: Met otrexate Cyclosporine 12-24 mont s Acitretin of eac step 3 agent 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)
66 Keratolytics = ƠSKIN LIFTERSơ
Helps remove scales and reduce hyperkeratosis Salicylic Acid 2-6% Enhance absorption of other drugs AE: N/V, tinnitus, hyperventilation (rare =salicylism)
67 Tars
Coal Tar ƛ 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%)
68 Coal Tar
Problems with coal tar: Smell Sting Stain Sensitize
69 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 Koebnerƞs 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
71 Corticosteroids
Level of Potency Corticosteroid Commercial Products
Ultr -high H l bet s l pr pi n te Ultr v te cr / int l bet s l pr pi n te Temov te crm/oint Bet eth s ne dipr pi n te Diprolene oint Difl r s ne di cet te Psorcon oint
High H lcinonide Halog crm mcinonide ylocort oint Bet meth sone dipropion te Diprolene AF crm Momet sone 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 73 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
74 Corticosteroids
Adverse Effects: (esp. with occlusion) Systemic absorption Dermal atrophy Telangiectasis Ecchymoses Peri-orbital acne Poor wound healing Pyogenic infections
75 Vitamin D3
Isolated from cod liver oil in 1936 Made in human skin through reaction: 7-dehydrocholesterol & UV light Calcitriolƞs properties in psoriasis:
1. Increase cellular differentiation
2. Inhibits cellular proliferation
76 Vitamin D3
Adverse Effects: Hypercalcemia Hypercalciuria Mild calcitriol intoxication: renal stones Not for long term use, therefore analogues were developed
77 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
79 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 q blood flow; chronic form E 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 Ingramƞs regimen (Anthralin) Goeckermanƞs 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 cellsƦinhibiting growth of cells.
3. Increased apoptosis of activated T-cells
104 Oral PUVA
Psoralen = ƠPơ 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