Psoriasis

Review Status: Internally reviewed

Figures:


Psoriasis vulgaris1-1	Psoriasis vulgaris1-2

　

Click on the small images to view in more detail.

Figure 1.Psoriasis of the scalp

Figure 2a.Psoriasis of the scalp

Figure 2b.Psoriasis of the scalp

Figure 3.Psoriasis : Trunk

Figure 4a.Psoriasis: Trunk

Figure 4b.Psoriasis: Trunk

Figure 4c.Psoriasis: Trunk

Figure 5a.Psoriasis: Back

Figure 5b.Psoriasis: Back

Figure 6a.Psoriasis: Back

Figure 6b.Psoriasis: Back

Figure 6c.Psoriasis: Back

Figure 7a.Psoriasis: Back

Figure 7b.Psoriasis: Back

Figure 7c.Psoriasis: Back

Figure 8.Psoriasis: Hand

Figure 9a.Psoriasis: Finger

Figure 9b.Psoriasis: Finger

Figure 9c.Psoriasis: Finger

Figure 10a.Psoriasis: Thigh and Knee

Figure 10b.Psoriasis: Thigh, posterior view

Figure 11.Psoriasis: Knee

Figure 12a.Psoriasis: Ankle, anterior view

Figure 12b.Psoriasis: Ankle, anterior view

Figure 12c.Psoriasis: Ankle, anterior view

Ps41	Ps42	Ps43	Ps44	Ps45	Ps46
Ps47	Ps48	Ps49	Ps50	Ps51	Ps52
Ps53	Ps54	Ps55	Ps56	Ps57	Ps58
Ps59	Ps60	Ps61

Definition:

A common, genetically determined, inflammatory and proliferative disease of the skin, the most characteristic lesions consisting of chronic, sharply demarcated, dull-red scaly plaques, particularly on the extensor prominences and in the scalp. The disease is enormously variable in duration and extent and morphological variants are common.

　

Incidence and prevalence:

1.Racial and ethnic variations:

A common genetically determined dermatosis with an prevalence of --0.18~0.3％in Chinese

--1~1.4％in USA

--1.43~2.9％in North Europe

--0％in Latin American Indian

In Singapore, India, Chinese and Malays Age of onset:

Females tend to? develop psoriasis earlier than males.
The age of onset reveals two peaks:

--early at 16~22 years

--later at 57~60 years

Patients with a family history of psoriasis tend to have an earlier age of onset.

Familial tendency for psoriasis:

Psoriasis in parents

psoriasis in?

siblings ％

Nil

One

Both

7.8

16.4

Sex ratio:

A greater incidence in young females than young males.
Adult men =Adult women

Etiology and pathogenesis:

Genetic predisposition

- Single gene autosomal dominant inheritance.
- Some studies showed the inheritance may be multi-factorial.
- HLA phenotype most strongly associated with psoriasis.
- - --HLA-B13
  - --HLA-B17
  - --HLA-Cw6
- Enviromental factors also contribute to the etiology.

Provocation and exacerbation:

Trauma:

Koebner and reverse Koeber phenomenon.
All-or-none phenomenon

Infection:

Streptococcal infection, especially in the throat, in provoking acute guttate psoriasis.
Continuing, subclinical streptococcal infection might be responsible for refractory chronic plaque psoriasis. --Additional administration of rifampicin with penicillin or erythromycin has been shown to markedly improve the skin lesions of all of patients with streptococcus-associated psoriasis unresponsive to penicillin or erythromycin alone.

3.Endocrine factors:

Peaks of incidence at puberty and at the menopause.
Improve in pregnancy, worse in postpartum.
Generalized pustular psoriasis may be provoked by pregnancy and may exacerbate premenstrually, and may also be provoked by high dose estrogen therapy.

4.Climate (sunlight / temperature):

Sunlight is generally beneficial, but small minority of psoriatics are provoked by strong sunlight and suffer summer exacerbations in exposed skin.
The prevalence of photosensitivity was estimated at 5.5％.?--Photosensitivity in psoriasis was significantly associated with skin type I, advanced age and female sex.

5.Metabolic factors:

Hypocalcemia
Dialysis

6.Drugs:

The most frequent associations included the administration of lithium, β-adrenergic blocking agents and antimalarials, calcium channels blockers, and the withdrawal of systemically administered corticosteroids.
The possible exacerbating effect of NSAID is of particular importance, but they still don*t have an obvious direct adverse effect on psoriasis.

7.Psychogenic factors:

There is evidence that the severity of psoriasis may depend on prior stress.

8.Alcohol:

Heavy drinking at a level liable to be detrimental to health was found significantly more commonly in male patients with severe psoriasis than in other psoriasis sufferers. It is possible that excessive alcohol consumption may lead to reduced therapeutic compliance, and also that it is a symptom of stress caused by severe skin disease.

9.Acquired immunodeficiency syndrome (AIDS):

The prognosis of AIDS in patients with psoriasis also appeared poor, but the mechanism is still unclear.

Pathogenesis:

1.Hyper-epidermopoiesis, rapid DNA synthesis:

Cyclic nucleotides:

--decrease cAMP, increase cGMP or cGMP/cAMP ratio.

--certain regulatory subunits (RI and RII respectively) of cAMP-dependent protein kinases I and II in fibroblasts from psoriatic versus nornal subjects.

Calmodulin:?Increased biologically active or immunoreative calmodulin (low calcium) has been found in samples from lesional psoriasis skin by several groups.

Growth factors:

--increase TGF-α, EGF receptor, IL-6

--there is shortening of the epidermal germinative cell cycle, an increase in the number of cells in the proliferative pool, and marked shortening of the epidermal turnover time in psoriatic lesions.

Proto-oncogenes:

--The increased expression in psoriatic lesional extracts of RNA for the proto-oncogenes Ki-ras, myc, fos, and abl has been reported.

2.Metabolic:

Leucocyte attractants in psoriasis:

--Arachidonic cascade :LTB4 elicits the formation of intra-epidermal neutrophil microabsxesses.

Polyamines:

--It may induce epidermal proliferation in vivo, and the activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in the synthesis of the polyamines, is increased by proliferative stimuli such as the tumor-promoting phorbol ester, UVB irradiation and hair plucking.

Proteinases:

--Some proteolytic enzymes such as plasminogen activator, may play a role in cellular activation, division and escape from contact inhibition.

Phosphatidylinositol:

--Phosphatidylinositol (PI) specific phospholipase C activity was found to be elevated in psoriatic lesional samples.

--PIP2 =＞DAG+IP3

intracellular calcium release

activation of PKC

--PKC activity has been reported to be significantly decreased in psoriatic skin.

3.Immunological mechanisms:

Activated T-cell expressing surface HLA-DR molecules and IL-2 receptors.

Lymphocytes attracted by locally produced chemotactic factors may release γ-interferon which in turn may induce the expression of HLA-DR and ICAM-1 on keratinocytes.=＞mononuclear cells bind to keratinocyte=＞cytokine release and result cellular activation

4.Basic research:

l Irregular epidermal proliferation and increased mitotic figures in keratinocytes, superficial vascular dilatation and proliferation, and infiltration of lesions with leucocytes including neutrophils, lymphocytes and monocyte / macrophages.

Histopathology:

Diffuse parakeratosis
Hypogranulosis poor differentiation
Regular acanthosis rapid mitosis
Tortuous, dilated vessels
Spongiosiform pustules of Kogoj
Microabscess of Munro

Clinical features:

1. Modes of onset:

Acute guttate psoriasis: children or young adult.
Most forms of psoriasis: before the fourth decade.
Pustular psoriasis of the palms and soles is extremely rare before adult life.
Post traumatic from: young, athletic men
Flexural lesions: obese, middle-aged subjects or pre-existing intertrigo.
Psoriasis which limited to the groins, perineal and perianal regions: men in the 20~50 age group.

2. Particular clinical signs:

Koebner or reverse Koebner phenomena
Auspitz's sign
Wonoroff ring(Figure 4a , Figure 4b , Figure 4c , Figure 5a , Figure 5b )

3. The morphology of the common chronic stable plaque (psoriasis vulgaris, nummular psoriasis)

Erythema which is full, rich red (salmon-pink) to orange-brown --D/D: eczema, seborrheic dermatitis, lichen simplex, lichen planus.
Silver white scale(Figure 11 , Figure 12a , Figure 12b , Figure 12c )
Well -defined, with a sharply delineated edge
Thickening characteristic of the psoriasis causes the lesions to be raised from the adjoining skin and easily palpable.
Hue/opacity papules
Discs and plaques of varying sizes are often found on the trunk and limbs(Figure 4a , Figure 5a , Figure 11 ). There may be any number of lesions or only a single one.
Pustules may appear

Clinical variants:

1. Guttate psoriasis:

Children and young adults who after acute streptococcal infections.
Shower of small lesions, appearing more or less generally over the body.
Often appear on the trunk and proximal part of the limbs, rarely on the soles.
Tendency of regression and recurrence.
Diagnosis:

--nature of the scaling

--general distribution

--preceding infection

D/D: multiple small scaling:; --psoriasiform drug eruption
　: --secondary syphilis; 　; --pityriasis rosea

　
2. Rupioid, elephantine and ostraceous psoriasis: Plaques associated with gross hyperkeratosis.
　
3. Erythrodermic psoriasis:

Type 1: Extensive chronic plaque psoriasis

--Erythroderma may occur as initial manifestation of psoriasis, or gradually or suddenly developed in a pre-existed psoriasis
--May follow sensitivity / irritation to topical reaction
--Widespread of follicular lesions during regression may indicating an impending relapse

Type 2: Unstable psoriasis

--May occurred at any time, unexpected

--Frequently in arthropathic type, or general pustular psoriasis, induced by infection, hypocalcemia, tar or corticosteroids.

--Frequent relapse is the feature

--The patient is febril and ill, the course is often tumultuous or prolonged, and there is an appreciable mortality.

--Severe itching

Metabolic complications of erythroderma:

--Universal inflammation as exfoliative dermatitis may induce the following:

heat loss and leading to hypothermia.
hypohidrotic or anhidrotic, urine outpet tends to drop
dehydration
compensatory increases in body heat production
hyperthermia
skin blood flow, blood volume and cardiac output may all be increased and lead to failure of the cardiovascular system
malabsorption =＞dermatogenic enteropathy
loss of protein =＞hypoalbuminemia =edema
loss of iron =＞mild anemia

Modification by site:

1. Scalp:

Usually no hair loss, except in erythroderma
Pityriasis amiantacea or rupioid
Very thick plaques develop, especially at the occiput.
Diffuse involved or multiple discrete plaques of varying size.
Hair line usually predominant.

2. Penis:

A solitary patch on the glans of the uncircumcised male lacks scales, but its color and well-defined edge are usually distinctive.
Need biopsy to R/O erythroplasia or Zoon's plasma cell balanitis.

3. Flexural (inverse) psoriasis:

Groins, vulva, axilla, submammary folds, gluteal cleft and other body folds is commoner in older adults than children.
Scaling is greatly reduced or absent.
The surface has a glazed hue and fissuring at the depth of the fold is common.
The edges are usually well defined unless secondary infection or medicament dermatitis.
D/D with infective or seborrheic dermatitis when the lesions are on the retro-auricular fold or the external auditory meatus.

4. Hands and feet:

Typical scaly patches on which a fine silvery scale.
Relationship to trauma or occupational irritants.
D/D with lichen simplex, hyperkeratotic eczema, pustulosis. Psoriasis has a sharply defined edge and absence of vesiculation.

5. Nail:

Frequently in psoriasis arthropathica.
Pitting in 25~50％or more.
Spots of "oil-drop"
Discoloration, subungual hyperkeratosis, ridges / grooves, onycholysis

Atypical forms:

1. Linear and zonal lesions

2. Seborrhoeic psoriasis

3. Mucosal lesions

4. Ocular lesions

Associations:

1. Other skin diseases:

seborrheic dermatitis

lichen simplex l lichen planus

pemphigoid

pemphigus

neurofibromatosis

actinic reticuloid

P-J syndrome

vitiligo

viral warts

2. Arthritis

3. Gout

4. Hypocalcemia

5. Intestinal disease and malabsorption

6. Cardiovascular disease

Complications:

1. Infection

2. Arthritis

3. Alcoholism

4. Nephritis and renal failure

5. Hepatic failure

6. Apical pulmonary fibrosis

7. Amyloidosis

Differential diagnosis:

1. Seborrheic dermatitis

2. Eczema

3. Lichen planus

4. Lichen simplex

5. Pityriasis lichenoides chronica

6. Candidiasis

7. Tinea cruris

8. Pityriasis rubra pilaris

9. Secondary syphilis

10. Porokeratosis

11. Bowen's and Paget's disease

12. Penile erythroplasia

13. Erythema annulare centrifugum

14. The annular migratory necrolytic erythema associated with carcinoma of the pancreas

15. Subcorneal pustular dermatosis

16. Psoriasiform drug eruptions

17. Parakeratosis pustulosa

Course and prognosis:

1. Guttate attacks carry a better prognosis than the others.

2. An early onset and a family history of the disease appear to worsen the prognosis.

Relapse:

1. Relapse is the rule, however completely the lesions are treated and by whatever method.

2. Severe cases can be maintained in prolonged remission by the use of MTX, PUVA or cyclosporin.

Management:

1. Local therapy:
Tar therapy
- Daily application of 2~5％crude tar, combined with a tar bath and UV light, has been a mainstay of in-patient treatment.
- Tar alone is certainly active in psoriasis as is UVB alone.
- Coal tar seems to sensitize the skin to UVA but not to UVB and pototoxicity is of photodynamic type.
- A combination of 5％crude coal tar and dithranol was found to be as effective as dithranol alone when used in short contact treatment of psoriasis.
- Folliculitis is the commonest side-effect.
- There was a significantly greater risk of skin cancer in psoriatic patients treated with high exposure coal tar and UV light therapy, than in matched patients treated with smaller dose therapy. The increased incidence of malignancy may, therefore, depend on exposure to high dose UVB.
- Contraindications:

--erythrodermic or generalized pustular psoriasis
--pre-existing folliculitis
--severe acne

Dithranol (anthralin):

Tar bath =＞ suberythema UVB =＞ dithranol paste (combine therapy is better than single therapy)
Dithranol past is not suitable for the head and neck, flexures or genitalia, where it is liable to spread and is too irritant. Short contact therapy (10 min daily) may be effective and less irritant.
The drug has the great virtue of lacking systemic toxicity.
Leaving deep brown staining.
Side-effect: folliculitis

Corticosteroids:

Choose to use on face and neck, flexures and genitalia. They are also used in unstable, erythrodermic and generalized pustular psoriasis in preference to tar or dithranol.
The merits are ease of application and removal, lack of irritancy and the absence of staining of skin or linen.
The hazards: topical steroids under occlusion do have a limited place in the management of recalcitrant psoriasis of the scalp, hands, feet and other areas.
Plasma cortisol levels are easily suppressed by the most potent preparations or high doses.
CPotent ones are likely to be needed on the scalp and knuckles particularly. onversely, the flexures and inner thighs need much weaker products.

# Intralesional corticosteroid therapy:

Triamcinolone hexacetonide or triamcinolone acetonide can be infiltrated intradermally into localized psoriasis lesions by needle injection. It is used in troublesome small, resistant lesions on the backs of hands, especially the knuckles, intensely pruritic small plaques or lichenoid lesions.

Treatment of the scalp:

Tar-containing shampoos =＞ cream formulations of dithranol =＞ if fail, corticosteroid scalp lotion or gels should be drenched overnight with a coconut oil based tar and salicylic acid pomade which is shampooed out once or even twice daily.

Topical or intralesional cytostatic therapy:

Mechlorethamine
Thiotepa
Fluorouracil
Alkylating agent lomustine
Hydroxyurea
Topical MTX

Dialysis and related procedures:

The clearing of incidental psoriasis during hemodialysis for uremia was reported in 1976. Dialysis could favorably influence psoriasis in patients with normal renal function.

Peritoneal dialysis is more effective than hemodialysis.
Cardiopulmonary bypass oxygenation
Extensive exchange with fresh frozen plasma
Hemofiltration

Occlusive dressing alone:

Prolonged occlusion with various tape products including Band-Acid.
Prolonged application of the adhesive hydrocolloid occlusive dressing.
Side-effects: hyperpigmentation, pain on removal of dressings, Koebner response or offensive odor.
It is the management of limited psoriasis.

Phototherapy:

Goeckerman first thoroughly documented the ability of crude coal tar applications followed by exposure to UV radiation to clear psoriasis.
Continued maintenance UVB therapy after initial clearance with UVB significantly increased the duration of disease control. An average of six treatments per month.
Selective UVB phototherapy (SUP) was introduced in Europe using UV sources with peak effective output in the 300~320 nm range. The excluded shorter wavelengths are also those most capable of causing DNA damage so the carcinogenic hazard may be reduced.
Low intensity SUP (LISUP) -home use
Fluorescent lamps with negligible UVC emission
In relation to possible carcinogenic hazards.
Side effects: therapeutic doses of UVB impair delayed hypersensitivity responses to dinitrochlorobenzene and mechlorethamine and may increase urinary excretion of mutagens. Prevalence of senile cataract is correlated with climatic UV exposure.
Very large doses of UVA alone may improve paoriasis and enhancement of UVB responses by UVA has been claimed.
UVB therapy is valuable for discoid psoriasis and may be especially valuable in guttate and seborrheic patterns.

2. Systemic therapy

Corticosteroids:

The fluorinated forms such as triamcinolone and betamethasone have more effect on psoriasis than prednisolone.
Withdrawal the drug will induce psoriasis to relapseor may rebound. The rebound may take the form of widespread amall-patterned eruprive psoriasis often involving the face and backs of hands.
Systemic steroids should not be used in the routine care of psoriasis.

Methotrexate:

Orally, intramuscularly or intravenously.
Mechanism:

--competitive inhibition of dihydrofolate reductases, exerting a stronge antimitotic action on the epidermis.

--inhibits PMN chemotaxis

MTX may be given as a single weekly oral dose, occasionally fortnightly.

During or after therapy, the renal, hepatic and marrow function tests are very important.

Contraindications:

--anemia, thrombocytopenia and leucopenia, active infection, peptic ulceration, ulcerative colitis, alcoholism, immunodeficiency, pregnancy, lactation and an unreliable patient.

Toxic effects:

--transient anorexia, nausea and dyspeptic pain.

--bursting headaches

--burning sensations in the psoriasis plaques --on the marrow: leucopenia, thrombocytopenia, folate-deficient megaloblastic anemia.

--modest thrombocytopenia, low to normal WBC count

--hetapotoxic, causing fibrosis and cirrhosis

--oligospermia in men

--abortifacient and teratogenic in early pregnancy

Risk factors:

--liver disease

--impaired renal function

--DM

--obesity

--increased age

It is particularly valuable in the chronic erythrodermic and generalized pustular forms.

In the event of accidental overdosage or unexpected acute toxicity, folinic acid should be given intramuscularly in full dosage.

Combined with:

--UVB

--PUVA

--folinic acid

--etretinate

--colchicine

in order to reduce dosage and toxicity of each modality.

Hydroxyurea:

It blocks the conversion of ribonualeotides to deoxyribonucleotides by interfering with the enzyme ribonucleosidediphosphate reductase.
Marrow toxicity.
Less effective than MTX.
Indication: patients needing systemic treatment and who are resistant to MTX or develop side-effect.
Virtue: less frequent cause of anorexia, nausea and hepatotoxicity.
Side-effect:

--fall in hemoglobin

--macrocytosis

--cutaneous vasculitis

--diffuse hyperpigmentation

--actinic psoriasis

--alopecia

--psychological effcts

Razoxane:

It affects only cells in the mitotic cycle, acting in the late premitotic and mitotic phases. It is capable of normalizing the vasculature of certain proliferating tumors. Initial response is rapid and optimal response may take 2 to 3 months.
Toxicity:

--bone marrow toxicity (microcytotic anemia)

--GI intolerance

--hair loss

--leg ulceration

--hepatotoxicity

--association with AML, SCC, multiple BCC, B-cell lymphoma

Thioguanine:

Bone marrow toxicity

Retinoids:

Vit. A effects on epithelial differentiation and the toxicity of hypervitaminosis A is well known. Dificiency causes cutaneous hyperkeratosis and squamous metaplasia of mucous membranes.

# Etretinate:

Resolution of:

--psoriasis vulgaris

--pustular psoriasis

--erythrodermic psoriasis

--exfoliative and plaque psoriasis

Psoriasis vulgaris may be less responsive and is often combine with :

--etretinate and long-term MTX

--corticosteroid cream

--dithranol

--tar

--selective UVB phototherapy (SUP)

--PUVA

Side-effect:

--lipophilic and progressively accumulates in the subcutis

--teratogenic

--hypertriglyceridemia

--radiographic spinal changes

--dryness of the lips, nose, eyes, mouth, throat or vagina

--painful exfoliative cheilitis, urethritis, balanitis, gingivitis, peeling of the finger-tips and corneal ulceration.

--rhagades, palmoplantar desquamation, burning sensations in the skin.

--joint stiffness and synovitis

--night blindness

Etretinate is very valuable in generalized pustular psoriasis.

Contra-indications:

--active liver disease

--pre-existing hyperlipidemia

# Isotretinoin (13-cis-retinoic acid):

Improve generalized pustular psoriasis
Less effective than etretinate in the treatment of chronic plaque psoriasis.

# Acitretin (formerly etretin):

Effective: acitretin=etretinate
Tolerance: etretinate>acitretin
There is an advantage in combining a retinoid with PUVA.

Photochemotherapy:

　
Definition:

Successful use of oral 8-methoxypsoralen (8-MOP) and UVA led to intense interest and the coining of the terms "photochemotherapy" and "PUVA".

Methodology:

--It is arbitrary.

--Liquid form produce higher, earlier peak levels of drug in the plasma and more reproducible plasma concentrations.

--Absorption being delayed and reduced by a fat-rich meal.

--Treatment is given two to four times weekly.

Eye protection

Patient selection:

--Contra-indications: renal, hepatic or severe cardiovascular disease, cataract formation, pregnancy, children under 18 years, or pre-existing light-aggravated disease such as SLE or porphyria.

PUVA should only be considered as a primary treatment in those patients over 55 years where psoriasis covers at least 20％of the body surface, and who cannot be controlled by conventional topical therapy.

Results:

--excellent in discoid psoriasis vulgaris.

--PUVA is also of value in generalized pustular psoriasis, erythrodermic psoriasis, chronic palmoplantar pustular psoriasis and nail psoriasis, but succuss rates are much lower in these atypical patterns of disease.

Patient monitoring:

--regular blood count

--renal and liver function tests

--eye examination

Combined therapy:

--etretinate or acitretin

--dithranol

--topical corticosteroids

--cytotoxic drug

Adverse effects of PUVA:

--Erythema and frank sunburn are the commonest effects.

--itching

--cataract

--Immune function abnormaly (reduce T-cell and its function, inhibition of lymphocyte DNA synthesis, delayed hypersensitivity responses)

--nausea

--pruritis

--mild facial dermatitis

--pigmentation

--photo-onycholysis

--bullae of generalized pemphigoid

--hypertrichosis in females

--lichenoid eruptions

--actinic keratosis

--superficial actinic porokeratosis

--LE-like syndrome

The carcinogenic hazard of PUVA:

--It is undisputed that solar UV radiation is a major etiological factor in SCC, BCC and malignant melanoma in humans. Psoralens are known to be mutagenic and DNA damage has been induced by PUVA.

--PUVA may induce AML and a preleukemic state.

PUVA using other psoralens:

--5-MOP

--Trimethylpsoralen

--3-carbethoxypsoralen

PUVA therapy with topically applied psoralens:

--8-MOP

--Trimethylpsoralen

--Advantage: avoidance of nausea

--Disadvantage: risk of severe local phototoxic reactions with blistering, and the production of unsightly, patchy pigmentation.

Cyclosporin (Cyclosporin A, CyA):

Its inhibitory effects on T-cells, a possibility which has substantially affected attitudes towards pathogenic mechanism in psoriasis.
It is active orally and it should be given only to patients with sufficiently severe disease.
Contra-indication:

--renal dysfunction

--uncontrolled hypertension

--past or present malignancy

--history of epilepsy

--acute infection

--pregnancy

--lactation

--immunosuppressive therapy

--concomitant therapy with nephrotoxins

--previous serious side-effect from CyA and known ----hypersensitivity

Relative contra-indication:

--abnormal liver function

--malabsorption

--drug or alcohol abuse

Withdrawal =＞severe psoriasis relapse within weeks

Side-effect:

--dose-related hypertension

--nephrotoxicity

--increase the risk of malignancy

Miscellaneous oral and topical agents:

Vitamin D3 (effctive: orally=topical)

--inducing keratinocates differentiation and inhibition of T-cell proliferation.

5-Lipoxygenase inhibitors

Fish oil

--interference with arachidonic acid metabolism.

Zidovudine (azidothymidine)

Systemic therapy for severe psoriasis: conclusions

Pustular forms of psoriasis:

1. Definition:

Neutrophilic accumulation in the epidermis is characteristic of all types and patterns of psoriasis and histologically all psoriasis is "pustular".

2. A convenient classification is as follows:

Localized pustular psoriasis:

chronic palmoplantar
acute palmoplantar (pustular bacterid)
acrodermatitis continua

Generalized pustular psoriasis:

acute
of pregnancy
infantile and juvenile
circinate
localized (not hands and feet)

Localized pustular psoriasis:

1. Chronic palmoplantar pustular psoriasis (PPP)

Definition:

A common condition in which erythematous and scaly plaques studded with sterile pustules persist on the palms or soles. The disease is chronic and very resistant to treatment.

Pathogenesis:

Maybe association with psoriasis vulgaris or has family history of it.

HLA-B13 (-)

HLA-B17 (-)

Provocative factors:

Lithium
Tonsils is a site of relevant focal infection.

Clinical features:

Adults, starts in the fifth or sixth decade or earlier
A modest preponderance of women.
one or more well-defined plaques
Hands: thenar eminence > hypothenar eminence or central palm or distal palm
Feet: instep, the medial or lateral border of the foot at the level of the instep or the sides or back of the heel
Symmetrical on the hands or feet is common
Dusty red and often scaly
Pustules are present, the desiccated pustule is exfoliated.

Differential diagnosis:

Tinea
Secondary infection of eczema
Chronic allergic contact dermatitis
Chronic acropustulosis

Prognosis:

The usual course is prolonged.

Temporary spontaneous remission

2. Acute palmoplantar pustular psoriasis:

Rare, acute, monomorphic eruption of sterile pustules occurring on all aspects of the hands and feet.

Distribution:

palms, soles, and palmoplantar aspects of digits or dorsa of the hands and feet.

The term "bacterid" implies that the eruption is provoked by a remote bacterial infection.

D/D: acute leucocytoclastic vasculitis with immune complex deposition.

3. Acrodermatitis continua

Definition:

A chronic sterile pustular eruption affecting initially the tips of fingers or toes which tends slowly to extend locally but which, in adults, may evolve into generalized pustular psoriasis.

Clinical features:

Children, female is common
starts on finger or thumb more often than on a toe
Koebner phenomena or infection induced
bordered by a fringe of undermined epidermis, irregular, often sodden and preceded by a line of vesiculopustules.
slow proximal extension
The nail plate may be completely destroyed.
osteolysis of the tuft of the distal phalanx
digits' end may become wasted and tapered, like scleroderma.
Cold weather may be exacerbation
evolve into generalized pustular psoriasis, especially in the elderly.

Differential diagnosis:

staphyloderma
pulp infection
herpetic whitlow
tinea
contact dermatitis
candidiasis
parakeratosis

Histopathology:

Intra-epidermal pustule packed with neutrophils.

Management:

Topical therapy:

--tar-impregnated occlusive bandages

--topical corticosteroid

--PUVA

Oral therapy:

--tetracycline

--clomocycline

--colchicine

--clofazimine

--sulphapyridine

--dapsone

--MTX

--hydroxyurea

--oral corticosteroid

--etretinate

--CyA

Radiotherapy

Generalized pustular psoriasis:

Definition:

Generalized pustular psoriasis (GPP) is an uncommon variant of psoriasis vulgaris in which an acute, subacute or occasionally chronic eruption has sterile pustulosis as its central feature.

Relationship to psoriasis vulgaris:

Patients may have phases of ordinary psoriasis before or after the GPP.

Provocation factors:

Von Zumbusch's (acute) original patient was provoked by irritating topical therapy.
coal tar and dithranol
infection
pregnancy
hypocalcemia
drug: especially corticosteroid
Withdraw of systemic steroid

HLA-B27(+)

Histopathology:

The inflammation is more intense in acute GPP than the other types.
lymphocytes infiltration
vessels edema
spongioform pustule formation (Kogoj)
acanthosis with elongation of rete ridges.
parakeratosis

1. Acute generalized pustular psoriasis (von Zumbusch):

Clinical features:

Typical type: early onset, develops into pustular psoriasis after some years, after provocation by steroid withdrawal.
Atypical type: later onset, acral or flexural in distribution. A rapid and apparently spontaneous progression to the generalized pustular form follows.
Burning erythema that spreads in hours to result in large areas of fiery-red skin.
pin-point pustules =＞clusters
lakes of pus, isolated pustules, circinate lesions, plaques of erythema with pustular collarettes or a generalized erythroderma.
fever, generalized weakness, severe malaise, leukocytosis
Nails: thickened or separated by subungual lakes of pus.
buccal mucosa and tongue may be involved.
Remission occurs within days or weeks, but relapses are common.

Complications:

hypoalbuminemia =＞hypocalcemia
oligemia
liver damage or even jaundice
deep vein thrombosis =＞fatal pulmonary embolism
staphylococcal infection
inflammatory polyarthritis
gross hair loss
telogen effluvium

Laboratory findings:

absolute lymphopenia
PMN reduce
plasma albumin, zinc and calcium may low
ESR is usually raised.
hyperlactatemia (secondary to hyperproliferation).

2. Generalized pustular psoriasis of pregnancy:

Definition:

A rare eruption, occurring especially in pregnancy with the features of generalized pustular psoriasis but with a tendency to be symmetrical and grouped and often starting in the flexures.

Pathogenesis:

before MC
progesterone or clomiphene will produce pustular exacerbation.
Impetigo herpetiformis with hypocalcemia is an entity separate from GPP occurring in pregnancy.

Clinical features:

last trimester but may be earlier in the first month of pregnancy
Risk of placental insufficiency leading to stillbirth, neonatal death of the child or fetal abnormalities.

Prognosis:

may recur

Laboratory findings:

hypocalcemia
lowered levels of vitamin D

Treatment:

mestranol/ethynodiol combinition orally

3. Infantile and juvenile pustular psoriasis:

male preponderance

Systemic symptoms are often absent and spontaneous remissions occur.

2~10 years at onset

Zumbusch pattern but annular and circinate forms are seen.

The prognosis is variable but the disease may terminate spontaneously or develop into more tractable psoriasis vulgaris.

　
4. Circinate and annular pustular psoriasis:

more characteristic of the subacute or chronic forms of widespread pustular psoriasis.

discrete areas of erythema which become raised and edematous.

slow centrifugal spread may mimic erythema annulare centrifugum.

pustules appear peripherally on the crest of the advancing edge.

5. Localized forms of generalized pustular psoriasis:

D/D:

palmoplantar pustulosis
acropustulosis
napkin psoriasis
psoriasis vulgaris following prolonged irritant topical therapy.
subcorneal pustular dermatosis
pustular lesions in Reiter's disease
acute pemphigus foliaceus
migratory necrolytic eruption of glucagonoma
bowel by-pass syndrome
Sweet's syndrome
Behcet's syndrome
staphyloderma
rampant impetigo
candidiasis
pustular drug druption

Management of generalized pustular psoriasis

Admission to hospital
Withdrawal of provocative factors
General measures:

--conservative treatments such as bedrest, sedation, bland local application, fluid and protein replacement, adequate ambient temperature.

Topical therapy:

--completely bland creams or lotions

--weak corticosteroid cream

--contra-indication: tar and dithranol

Systemic therapy:

--MTX

--razoxand

--dapsone or sulphapyridine

--corticosteroid (oral, parenteral, topical)

--etretinate alone or combine with PUVA

--PUVA

--cyclosporin

Prognosis:

Von Zumbusch psoriasis: prognosis good
GPP developing from acropustulosis: the worst prognosis
GPP of childhood: prognosis good GPP which onset late: poor prognosis, death is due to cardiac failure or resperatory infection.
Patients with preceding ordinary psoriasis had a better prognosis than those with atypical prepustular psoriasis.

Arthropathic psoriasis (Psoriatic arthritis):

1. 0.02~0.1％in population, 2~25％of psoriatics

2. Definition:

The association of psoriasis of the skin and/or nails with a peripheral and/or spinal arthropathy, and usually a negative serological test for rheumatoid factor.

3. Etiology and pathogenesis:

genetic

usually association with HLA-B27

enviromental factors

4. 40~60 years is the peak age

5. Clinical patterns:

asymmetrical DIP joints

arthritis mutilans with osteolysis of phalanges and metacarpals

symmetrical polyarthritis (RA-like)

oligoarthritis with tenosynovitis of hands

D/D: ankylosing spondylitis, psoriasis arthritis may with peripheral arthritis

nail dystrophy