Download consensus statement - Academy of Medicine of Malaysia

CONSENSUS STATEMENT
“THE MANAGEMENT OF PSORIASIS”
August 1996
By
PERSATUAN DERMATOLOGI MALAYSIA
(DERMATOLOGICAL SOCIETY OF MALAYSIA)
Prepared by
The Committee on Guidelines for Quality Care in Dermatology
Chairman/Editor
Dr Kim Weng Chow
FRCP
Secretary
Dr Gangaram Hemandas
MRCP
Members
Datin Dr Suraiya H Tun Hussein
FRCP
Dr Ain Tian Gan
MRCP
Dr Sushil K Ratti
MRCP
Dr Hon Nam Chew
FAAD
Dr Roshidah Baba
MRCP
Dr Kim Chye Yee
MRCP
CONTENTS
1.
2.
Psoriasis
Management of Psoriasis
1.1
Introduction
1.2
Definition
2.1
Rationale for Treatment
2.1.1 Scope of the Problem
2.1.2 Morbidity Issue
2.1.3 Mortality Issue
2.2
Diagnostic Criteria
2.2.1 Clinical Characteristics
2.2.2 Diagnostic Tests
2.2.3 Differential Diagnosis
2.3
Aims of Treatment
2.4
Principles of Management
2.5
Indications for referral to a Consultant Dermatologist
2.6
Levels of Care for Psoriasis Management
2.61 Office Treatment
2.62 Ambulatory (day care) Treatment
2.63 Hospitalisation (in-patient care)
2.7
Office Treatment
2.7.1 Topical Therapy
2.7.2 Summary of Topical Therapy
2.7.3 Physical Therapy
2.7.4 Systemic Therapy
2.7.5 Combination Therapy
2.8
Ambulatory Treatment (day care)
2.8.1 Introduction
2.8.2 Phototherapy (Ultraviolet B Irradiation)
2.8.3 Photochemotherapy (PUVA)
2.8.4 Combination Regimes with Phototherapy
2.8.5 Hand and Foot PUVA
2.8.6 Bath PUVA
2.8.7 Summary of Systemic and Physical Therapy
2.8.8 Additional services
2.9
Hospitalisation (in-patient care)
2.9.1 Indications for hospitalisation
2.9.2 Adjunctive Therapies
3.
Patient Education
4.
Use of Guidelines to Derive Audit Measures
5.
Supporting Evidence
6.
Disclaimer
7.
List of References
1. PSORIASIS
This Consensus Report reflects the best data available at the time of preparation. Caution should be exercised in
interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set
forth in this report.
1.1
INTRODUCTION
The Dermatological Society of Malaysia Committee on Guidelines for Quality Care is developing its guidelines of care
for our profession. The development of guidelines will promote the continued delivery of quality care and assist those
outside our profession in understanding the complexities and scope of care provided by dermatologists.
1.2
DEFINITION
Psoriasis is a chronic skin disease that is classically characterized by thickened, red areas of skin covered with silvery
scales. The extent of skin involvement can range from discrete, localized areas to generalised body involvement. The
joints, nails and mucous membranes may also be affected with the disease.
2. MANAGEMENT OF PSORIASIS
2.1
RATIONALE FOR TREATMENT
2.1.1 Scope of the Problem
Psoriasis affects 1% to 2% of the general population. It has no known cure and can affect all age groups and both sexes. It
may be symptomatic throughout life and may be progressive with age or wax and wane in its severity. Physical and
psychological disability produced by the disease may range from minor to total. In addition to classical plaque psoriasis, a
severe inflammatory form of the disease, erythrodermic psoriasis, or generalised pustular psoriasis may produce
involvement of the total body surface and may have associated systemic or constitutional manifestations.
2.1.2 Morbidity Issue
Patients with psoriasis have a disease that may be readily apparent to others because of the redness, scaling and
thickening of the skin. This disease can cause functional impairment, disfigurement of the skin and emotional distress.
The skin may itch, burn, sting and easily bleed in the areas affected with psoriasis. Severe involvement of the hands, feet
and nails may make even routine activities, such as walking or dressing difficult to perform. Up to 30% of patients with
psoriasis may have arthritic symptoms. Five to ten percent of these patients may experience functional disability from
arthritis of various joints. Persons with erythrodermic (generalised redness of the body surface) psoriasis usually have
difficulty in controlling body temperature. These and other factors directly related to psoriasis may cause a person to have
difficulty in work performance, problems with social rejection, sexual dysfunction and depression. Patients usually find
their disease more disabling than that diagnosed by their doctors.
2.1.3 Mortality Issue
Erythrodermic and generalised pustular psoriasis may be life-threatening because of systemic infections or cardiovascular
or pulmonary complications. Severe social rejection and morbidity with the disease has led to suicide.
2.2
DIAGNOSTIC CRITERIA
2.2.1 Clinical Characteristics
A history and complete total surface skin examination should be performed. The history, clinical appearance and location
of lesions are the most reliable indicators of the disease.
i.
The amount of scale, thickness of the lesion and degree of redness may vary depending on the area of the body
involved. The classic areas of involvement are scalp, face, elbows, knees, palms and soles, intertriginous folds and
genitalia. The lesion morphology may also vary and include papules and plaques of various sizes as well as pustules.
The surface area of skin affected may range from minimal to total body involvement. Severe cradle cap or diaper
dermatitis may be forerunners of psoriasis. Approximately 30% of patients have a family history of the disease.
ii.
Aggravating/Precipitating Factors
 Infections may precipitate and exacerbate the disease.
 Drugs, predominantly lithium, beta-blockers, antimalarials, alcohol or nonsteroidal anti-inflammatory agents may
aggravate the disease.
iii. Nails
Various degrees of nail deformity may be seen including pitting, onycholysis and subungual hyperkeratosis.
iv. Joints
Inflammatory changes can affect small or large joints either singly or in combination, producing a wide range of
arthritic changes and joint deformity.
v.
Ears
A moderate degree of scaling within the ear canals is common. In severe cases this may produce an impaction of
scale within the ear canal causing hearing impairment.
vi. Mucous Membranes
Psoriasis frequently involves the genitalia and may involve the lips, buccal mucosa and other mucous membranes.
2.2.2 Diagnostic Tests
Laboratory tests may include the following:
i.
Biopsy
Histology is sometimes used to differentiate psoriasis from other conditions (see "differential diagnosis"). The
pathology is usually, but not always confirmatory, particularly in guttate, palmoplantar or erythrodermic psoriasis.
ii.
Other tests
 Radiologic studies
 Serologic studies
 Culture for appropriate organisms
 Microscopic (potassium hydroxide) examinations
 HLA typing
2.2.3 Differential Diagnosis
Many diseases mimic psoriasis. These may include but are not limited to dermatitis, fungal infections, discoid and
subacute lupus erythematosus, lichen planus, mycosis fungoides, pityriasis rubra pilaris, Bowen's disease, parapsoriasis
and secondary syphilis.
2.3
AIMS OF TREATMENT
The majority of patients with psoriasis may be able to control their disease with treatment either prescribed or delivered in
a dermatologist's office. However, a significant number of patients may require specialized treatments and experienced
nursing care that would necessitate the use of an ambulatory treatment centre or admission to the hospital. Some of the
treatment periods may be prolonged because of the severity and extent of the disease.
Psoriasis is a chronic and recurrent disease that can be psychologically and physically disabling. The aims of therapy are:
i) Suppressive
ii) Preventive and
iii) Supportive
2.4
PRINCIPLES OF MANAGEMENT
The principles of management include:
 Confirmation of diagnosis - usually clinical and only rarely is a biopsy required
 Counselling of patient - on disease process, treatment options, importance of compliance and follow-up including the
non-contagious and non-cancerous nature of the disease
 Counselling of others as necessary, eg. spouses, employers, friends etc
 Use of anti-psoriatic medications
For successful management it is important to establish a good rapport with the patient from the outset. Management
should then be a two-way process with the patient as much involved as the doctor in the decision making process as each
have their own views about severity and importance of treatment.
2.5
INDICATIONS FOR REFERRAL TO A CONSULTANT DERMATOLOGIST






Diagnostic difficulty
Request for patient counselling or education, or both, including initial demonstration of topical treatment
Failure of topical treatment used appropriately for three months
Need for increasing amounts or potencies of topical corticosteroids
Need for systemic drugs
Generalised pustular or erythrodermic psoriasis (emergency referral)
2.6
LEVELS OF CARE FOR PSORIASIS MANAGEMENT
The management of psoriasis can be delegated via 3 levels of care
2.6.1 Office Treatment
2.6.2 Ambulatory Treatment (day care)
and
2.6.3 Hospitalisation (in-patient care)
By and large the majority of patients are managed by levels 2.6.1 and 2.6.2. Hospitalisation is only required for specific
indications.
2.7
OFFICE TREATMENT
This can usually be done on an outpatient basis and can be broadly divided into 3 main groups:
2.7.1 Topical Therapy
- tar, dithranol, calcipotriol, corticosteroids and others
2.7.2 Physical Therapy
- ultraviolet radiation (UVA/UVB)
- PUVA (Psoralen, Ultraviolet A Treatment)
2.7.3 Systemic Therapy
-
methotrexate
retinoids
sulphasalazine and others
hydroxyurea
cyclosporin
corticosteroid (only for specific indications)
2.7.4 Various combinations of 2.7.1, 2.7.2 and 2.7.3
This sequence generally defines not only the risk-benefit ratio but also the progression of therapy. Topical agents are
safest while systemic agents carry the greatest risk. Initial therapy is usually with topical agents followed by ultraviolet
radiation if the disease responds poorly and finally systemic agents. Some extensive cases may need phototherapy or
systemic agents from the beginning. The more severe cases such as erythrodermic psoriasis or acute generalised pustular
psoriasis will need inpatient treatment with close monitoring as it can be fatal. Often patients are on a combination of
treatment.
2.7
OFFICE TREATMENT
2.7.1 Topical
i.
ii.
iii.
iv.
v.
vi.
Emollient
Tar
Anthralin
Vitamin D3 and derivatives
Keratolytics
Corticosteroids
i. Emollients
Emollients are topical agents that smoothen and soften the stratum corneum. They have their effect, not by hydration of
the stratum corneum, but by a trapping mechanism that slows down the rate of transepidermal water loss.
 Emollients are an important component of therapy for psoriasis.
 They are particularly valuable in patients with dry skin and skin dryness aggravated by frequent bathing and
phototherapy.
 They appear to enhance the efficacy of phototherapy, possibly by altering the optical and UV- transmitting
characteristics of the stratum corneum.
 There is great personal patient preference for different emollients; it is advised that several names or samples be given
and patients be allowed to find the emollient that they are willing and able to use on a regular basis.
Examples






Vaseline
Petrolatum
Mineral oils
Urea
Glycerine
Others
ii. Tars
Coal tar suppresses DNA synthesis in the epidermis within the first few hours after its application. It has antiinflammatory and anti-pruritic effects.
Forms :
Crude tar
in ointment or solution 1 - 10%
Purified tar
Treatment Regimen
 Tar alone
-
Tar bath.
- Apply tar ointment on psoriatic plaques, face and flexures to be spared.
 Tar with phototherapy (Goeckerman Regimen)
-
Tar bath for 15 - 30 niinutes.
-
Followed by suberythemogenic UVB dosage or natural sunlight.
Tar ointment to psoriatic plaques at an initial dose of 1% and gradually step up every 2 - 3 days if patient tolerates.
- Leave tar ointment for 12 - 24 hours.
 Scalp
Tar containing preparations eg Ung Cocois Co
Side Effects
 Folliculitis
 Skin irritation
 Aggravation of Acne
iii. Anthralin
Anthralin slows proliferative rate of stem cell population; therefore it allows normal keratinisation. Although it is an
effective agent, it is not an ideal drug because of its irritating and staining properties. Regardless of these shortcomings, it
is an effective treatment for plaque psoriasis.
Treatment Regimen
 Routine Anthralin Therapy
Anthralin 0.1 per cent cream is applied to the affected areas daily at bedtime. Continue therapy until the lesion clears
and then taper the application.
 Short Contact Therapy
Anthralin 0.5 to 4 per cent cream is rubbed into the plaques. After 30 to 60 minutes the anthralin is removed by
washing or showering. An emollient or suitable corticosteroid may be applied after the treatment. Treatment is
scheduled daily and continues until the plaques have cleared. This regimen is for convenient anthralin therapy;
increased effectiveness of anthralin and it causes less staining of clothes
 Anthralin treatment of the scalp
Anthralin pomade is massaged on to the scalp at night and left in place overnight. Remove by shampooing in the
morning. This treatment can be daily initially but twice weekly is often sufficient. It is important to warn patients to
avoid eye contamination.
Side Effects of Anthratin
 Skin irritation
Some patients cannot tolerate strengths as low as 0.1% while others may tolerate more than 4%.
 Skin staining
Patients should be encouraged to identify staining as a sign of progress in treatment. The brown staining usually clears
2 - 3 weeks after stopping treatment.
Keratolytic agent such as salicylic acid can help to hasten the removal of this stain.
iv. Calcipotriol Trial
 It promotes differentiation of keratinocytes and inhibits proliferation leading to normalisation of the epidermal cells.
Calcipotriol is effective for mild to moderate chronic plaque psoriasis as it clears the psoriasis in 6 - 8 weeks.
Improvement is seen within 2 weeks. For some patients, further improvement is observed if treatment with
calcipotriol is extended up to 16 weeks.
Preparation
 Calcipotriol 50 mcg/g Ointment/Cream
Application
 Twice a day to psoriatic lesions.
 Weekly dose of Calcipotriol should not exceed 100 gms.
 Face and body folds to be avoided.
Calcipotriol has been used for up to one year without significant side effects.
Calcipotriol has also been used in combination therapy with UVB, PUVA, cyclosporin, methotrexate and retinoids in
moderate and severe psoriasis.
Side Effects
 Transient skin irritation.
 Potential hypercalcemia if recommended dose is exceeded.
v. Keratolytics
Keratolytics are agents that help to remove diseased scales or hyperkeratosis in psoriasis. They work by breaking down
and peeling off excess scales in the psoriatic areas.
Topical salicylic acid is the most frequently used keratolytic agent. It may be used alone or in conjunction with other
forms of therapy. The concentration range is between 2% and 10%. Caution is to be exercised when this agent is applied
extensively to body, particularly in children, since use may result in salicylism.
vi. Corticosteroids
Corticosteroids are thought to work by vasoconstriction decreased cell turnover and by their anti-inflammatory action.
Topical corticosteroids are of value for the treatment of psoriasis but as psoriasis is a chronic disease, long term use may
have untoward side effects. Therefore caution needs to be exercised in its usage. The most common complications are
systemic absorption, cutaneous atrophy and striae formation, and flare-ups, which may occur after the discontinuation of
treatment. Corticosteroids are the treatment of choice for psoriasis involving the face, hairline, and postauricular and
flexural areas.
More potent corticosteroids should be reserved for the treatment of the palms and the soles.
Choosing a steroid
Topical steroid is an adjunct to other accepted forms of topical therapy. Selection of steroid depends on:




Site of lesions to be treated
Severity of lesions
Age of patient
Steroid's inherent potency
Scalp
Steroid lotions, sprays and gels can be rubbed into the scalp more easily than cream and ointment and are to be
recommended in the treatment of scalp psoriasis.
Face
When psoriasis occurs on the face, mild steroid is recommended; the use of potent steroids on the face is to be avoided.
Extremities
Lesions on the extremities, particularly the lower extremities, are at times notoriously difficult. Potent steroids can be
used to treat a limited area and if necessary under occlusion.
Trunk
Topical steroid can be combined with anthralin or tar to reduce irritation or topical steroid cream can be applied in the
morning and anthralin or tar at night.
How much Topical Steroids to use?
Body Area to Treat
Your prescription for twice daily applications for seven days.
Adult
One arm
One leg
Hand and Foot
Trunk (front and back)
Head and Neck
14 g
28 g
14 g
56 g
14 g
As a rough guide, 1% surface area requires 0.5 gm per day based on twice a day application.
Children
The smaller the child the lesser topical steroid you use.
Never continue the use of topical steroid to prevent relapse.
Side Effects of Topical Steroids
General
Pituitary - adrenal axis suppression (rare)
Cushing's Syndrome
Local
Atrophy
Striae
Echymoses
Rosacea like dermatitis
Perioral dermatitis
Acne
Glaucoma
Secondary infection especially fungal
Rebound phenomenon
Body Folds
Since the skin in the body folds tends to be thin, one can treat areas like axillae, groins, genitalia etc. with low potency
steroids. Cream or gel is often better accepted than ointments.
Palms and Soles
Topical steroids are only mildly effective in the treatment of psoriasis on the palms and soles.
Nail Folds
The use of topical steroids on nail folds is often unrewarding. While Intralesional Kenacort is effective it is often painful
and should not be encouraged when lesions are many.
Intralesional Steroid
Intralesional therapy is rarely used in psoriasis except in experienced hands.
Triamcinolone acetonide, 2.5 to 10 mg per ml in a quantity of 0.1 to 1 ml, is used to infiltrate lesions on the scalp on
fingernails, or any small, stubborn plaques. Wait 6 to 8 weeks before retreating.
Summary of Topical Therapy
Table I - Topical Therapy
Emollients
Tar
Anthralin
Calcipotriol
Keratolytics
Topical corticosteroids
- mild potency
- mid potency
- maximum potency
Effectiveness
+
++
++
++
+
Remission
+
++
++
++
+
Possible side effects
+A
+ADE
++ADE
+AF
+AE
Comments
d,e,f
d,f
d,f
c,d
+
++
+++
+
+/++
++
+AB
++AB
+++AB
a,b
a,b,c,d
a,b,c,d,f
Effectiveness
:
+
Mild
++ Moderate
+++ High
Remission
:
+
< 1 month
++ 1 - 3 months
+++ > 3 months
Possible side effects
:
+
Mild
++ Moderate
+++ Severe
A : Inconvenience.
B : Topical corticosteroid side effects may be local and/or systemic and may include burning, irritation, itching, stinging,
erythema, folliculitis, skin atrophy, telangiectasia, hypertrichosis, acneiform eruptions, maceration, hyperglycemia,
hyperglycuria and manifestations of Cushing's syndrome; side effects tend to increase with increased potency.
C : Pain, discomfort, atrophy, telangiectasia and hypopigmentation.
D : Staining.
E : Irritation.
F : Potential hypercalcaemia if recommended dose is exceeded.
Comments
a. Tachyphylaxis
b. Increased risk of steroid side effects with increased potency, duration of treatment, and
total dosage.
c. Possibility of systemic absorption may limit use in children.
d. Avoid eye contact and intertriginous use in children.
e. Increased photosensitivity.
f. Avoid use in body folds.
2.7.2 Physical Therapy (Refer Table II)
Phototherapy
-
UVA
UVB
Refer to section 2.8
Photochemotherapy (PUVA)
2.7.3 Systemic Therapy
Systemic treatment should only be used by dermatologists or physicians familiar in its use in the treatment of psoriasis
i.
Indications for Systemic Treatment
 Failure of adequate trial of topical treatment
 Repeated hospital admissions for topical treatment
 Extensive chronic plaque psoriasis in elderly or infirm people
 Generalised pustular or erythrodennic psoriasis
 Severe psoriatic arthropathy
ii.
Available Systemic Treatment
 Methotrexate
- Oral
- Intramuscular
- Intravenous
 Retinoid
- Acitretin
 Sulfasalazine
 Hydroxyurea
 Cyclosporin
 Corticosteroids
In the vast majority of cases, this is not the treatment of choice because of a potential severe rebound of psoriasis and
steroid side effects. It is contraindicated except for certain selected cases, disabling psoriasis or psoriatic arthritis and
is usually limited to short-term use.
 Antibiotics
Useful in patients with evidence of cutaneous or systemic microbial infection or colonization especially in guttate
psoriasis associated with streptococcal pharyngitis.
i. Methotrexate
Methotrexate (MTX) is an effective antipsoriatic agent especially in acute generalised pustular psoriasis, erythrodermic
psoriasis, psoriatic arthropathy and extensive chronic plaque psoriasis in the elderly or infirm patients. It is to be used by
dermatologists and physicians who are familiar with its use in psoriasis.
Indications
The decision to administer MTX for the treatment of psoriasis should be individualized. It should be based on the
severity, amount of discomfort, degree of incapacity and general medical and psychological conditions. MTX is indicated
in the symptomatic control of recalcitrant psoriasis not responsive to topical therapy. Specific clinical indications include
the following:




Psoriatic erythroderma
Psoriatic arthritis
Acute pustular psoriasis of Von Zumbusch
Localized pustular psoriasis
 Psoriasis which is physically disabling eg. that of palms and soles
 Extensive plaque psoriasis
Relative Contraindications











Significant abnormalities in liver chemistry
Significant abnormalities in renal function
Pregnancy or nursing mothers (absolute contraindication)
Male or female infertility
Hepatitis active or recent
Cirrhosis
Severe anaemia, leucopenia and thrombocytopenia
Excessive alcohol consumption
Active infectious diseases eg TB
Overt or laboratory evidence of immunodeficiency syndromes
Patient who is unreliable/non compliant
In deciding the use of MTX, one must always keep in mind the risk benefit ratio.
Dosage
-
The drug may be administered orally, IM or IV.
The dose must be individually assessed.
It may be given as a single or three divided doses weekly orally, intramuscularly or intravenously.
A test dose of 2.5-5 mg may be administered to avoid early toxicity.
The range of oral dosages ordinarily is 7.5-25 mg/week
The range of IM/IV is 7.5-50 mg/week.
There must be appropriate monitoring of the blood counts weekly initially and monthly whilst on maintenance therapy.
Side Effects
The main side effects are bone marrow suppression and a long-term risk of hepatic fibrosis and cirrhosis, which is related
to a cumulative lifetime dosage. Conception must be avoided during the course of treatment and for one menstrual cycle
after stopping the drug.
Monitoring
Full blood count, measurement of blood urea, electrolytes, and creatinine concentrations; liver function tests; and clinical
examination of liver should be done weekly. The need for estimation should then be extended to two to three monthly
intervals and or when clinical need arises. There may be a transient rise of liver enzymes occurring in the first few days
after administering the dose.
Liver Biopsy
It is now established beyond all doubts that MTX is hepatotoxic, causing hepatic fibrosis and cirrhosis, the incidence of
which has varied in different series. The incidence is however low if the cumulative dose is less than 1.5 gms. In patients
with persistently deranged liver biochemistry or abnormal results on liver imaging, liver biopsy should be considered
before starting or continuing treatment. It is therefore recommended that a liver biopsy should be performed on patients
who have to be on long term MTX and this should be done soon after or before starting treatment and repeated after a
cumulative dose of 1.5 gms. Exceptions are made for those who are given short term treatment.
Drug Interactions
The following drugs may interact with MTX and increase its activity: alcohol, salicylates, cotrimoxazole, trimethoprin,
probenecid, phenytoin, retinoids, pyrimethanine and frusemide. Patients must be warned of concominant administration
of these drugs.
ii. Retinoids
This drug is available only to dermatologists and physicians licensed by the Drug Control Authority of Malaysia.
Indications
 Generalised pustular psoriasis (Von Zumbusch type)
- treatment of choice
 Acrodermatitis continua of Hallopeau
- treatment of choice
 Palmoplantar pustulosis
- as combined therapy when other treatments inadequate
 Erythrodermic (Exfoliative) psoriasis
- treatment of choice
 Extensive plaque psoriasis
- as combined therapy when standard treatment ineffective
- only considered under special circumstances
 Psoriatic arthropathy
- monotherapy
- to reduce dose of NSAIDS
Contraindications
 All female patients of reproductive age because retinoids are teratogenic
Exceptions:
- other treatments are ineffective or not feasible
- effective contraceptive used
 Raised serum lipids
 Liver disease
- cirrhosis, HBS Ag positive, abnormal liver function tests
Synthetic Retinoids Used
 Acitretin (Trade name: Neotigason)
Dosage and Duration of Treatment
Acitretin 0.5 - 1 mg/kg/day
- 1 mg/kg preferable as initial dose.
When condition is controlled, the dose is reduced to 0.25 - 0.5 mg/kg as maintenance for 3 months after
which discontinuation is considered.
- For combination treatment e.g. with UVB or PUVA, a lower dose of 0.25 - 0.5 mg/kg is used.
Side Effects
Cheilitis (chapped lips), dry nasal mucosa, hair loss, dry skin, skin fragility, palm/sole peeling, bruising, fingertip peeling,
thirst, nosebleed, sticky/clammy skin, bone/joint pain, myalgia, irritation of eyes, paronychia, pyogenic granuloma,
hyperlipidaemia, hepatitis.
TERATOGENICITY : The retinoids are highly teratogenic
SKELETAL TOXICITY: There is concern that long term etretinate therapy is associated with skeletal and ligamentous
calcification and hyperostosis (DISH syndrome: Diffuse Interstitial Skeletal Hyperostosis).
These appears to be a cumulative threshold dose of 25 - 30 gms Acitretin below which skeletal
toxicity is not seen radiographically.
Management Protocol
 Signed consent
- Both female and male patients.
 Pre-treatment Tests
- Full blood count, Liver function tests, Fasting serum lipid.
 Treatment Tests
- Repeat every 2 weeks during first 6 weeks' clearing doses.
- Repeat every 8 weeks when on low-dose maintenance dosages.
 Pregnancy Test
- Female patients: Pre-treatment pregnancy test or treatment started immediately after menses. Pregnancy test repeated
every month of therapy.
 Skeletal X-rays
- To exclude hyperostosis and ligamentous calcification if patient needs continued treatment after 12 months. Then
repeat yearly.
iii. Salazopyrine Sulphasalazine
Salazopyrine is a useful second-line drug in rheumatoid arthritis as well as in psoriatic arthropathy. It also appears to be
useful in moderate-to-severe plaque-type psoriasis. Its effectiveness is probably less than other systemic modalities such
as PUVA, methotrexate, or retinoids although 25% of patients have comparable efficacy. Its advantage is that although
adverse effects are relatively common, these are often not severe and generally reversible. Salazopyrine is also relatively
inexpensive.
Indications
Psoriasis not responding to topical therapy but not severe enough to warrant other more potentially toxic systemic
modalities.
Contraindications
G6PD deficiency and allergies to sulpha drugs.
Dosage
Initially 500 mg three times a day for 3 days, if no adverse effects increase dose to 1 gm three times daily. Maximum dose
4 gm/day. Dosages for psoriatic arthritis can be lower - 2 to 3 gm/day. Discontinue salazopyrine if no response by week 8.
Monitoring
Baseline - Full blood counts (FBC), liver function tests, urea, creatinine. Repeat blood counts at 2 nd and 4th week and the
rest at 4 weeks and periodically. A drop in haemoglobin during therapy is well documented. Discontinue treatment if
there is a drop of more than 2 gm haemoglobin at any stage; 50% or more reduction in total white cell count or
neutropenia of less than 3,000/mm3, platelet count less than 100,000/mm3.
Side Effects
The incidences vary between 5 - 50% but are generally mild. (Watkinson 1986) These include gastrointestinal upsets,
cutaneous eruptions, and haematological changes. Slow acetylators are more likely to develop adverse effects with sulpha
drugs. Only 15% of Asians are slow acetylators compared to 50% - 60% of Caucasians.
iv. Hydroxyurea
Although the role of hydroxyurea in the treatment of psoriasis has diminished in recent years, it has several advantages. It
is relatively inexpensive; dose schedules are simple, and has few contraindications and subject side effects. Patients with
hyperlipidemia, mild renal insufficiency, and cardiopulmonary disease who may tolerate other systemic therapy may be
managed with hydroxyurea. Its efficacy however is probably less than the other agents above, with a favourable outcome
of up to 63%.
Indications
- Patients unresponsive to topical therapies or UVB
- Patients not acceptable for PUVA, methotrexate, acitretin, cyclosporin A.
Contraindications
Absolute : Pregnancy/lactation, Drug allergy.
Relative : Blood dyscrasias, ongoing infection, unstable / fulminant psoriasis, psoriatic arthropathy (ineffective), and
hepatic / renal / cardiopulmonary disease
Dosage
Initial - 500 mg two to three times/day with food. Maintenance - 0.5 to 1.5 gm/day
Monitoring
Baseline
During Therapy
Discontinue therapy if
- Full blood count (FBC), liver function tests, urea & electrolytes, urinalysis.
- FBC's weekly for the first month, then every 2-4 weeks thereafter (A drop of 1-2 gm/dl of
haemoglobin is expected, as well as a rise in MCV). Periodic estimations of the renal and liver
function tests.
- Haemoglobin falls by 3 gm/dl or more; White cell < 5000; platelet count < 100,000/mm3; No
response after 8 weeks; Concurrent infection.
Adverse Effects
Hydroxyurea is usually well tolerated. Older patients are more prone to side effects:
Hemopoetic System
- this is the main limiting adverse effect, but irreversible bone marrow suppression has not been
reported with above doses
Gastrointestinal
- nausea and vomiting, occasionally mild hepatitis but no irreversible hepatic damage or fibrosis
Teratogenicity
- seen in animal models. Females of reproductive age will require adequate contraception
Cutaneous
- hyperpigmentation especially in sun-exposed areas; transient alopecia
Neoplasia
- rarely, second tumours with long term use.
v. Cyclosporin A
The efficacy of Cyclosporin A (CyA) in psoriasis is well established with clearance rates of over 90%. Provided that strict
guidelines are followed using dermatologic doses (< 5 mg/kg/day) it has been used with relative safety as monotherapy
for up to 2 years. However, long-term safety is still a concern especially with regards to nephrotoxicity and neoplasia. It
should only be used by dermatologists with expertise in its use. Careful monitoring is mandatory, preferably in
consultation with an experienced nephrologist. As with most therapies, severe psoriasis recurs after cessation of therapy,
often within 2 months. It can be used as a 'crisis buster' for very inflammatory disease, and as part of rotational therapies
in an effort to limit toxicities from the different systemic modalities.
Indications
Patients who have failed with:
 topical treatment
 ultraviolet radiation (UVL) treatment
 systemic treatment
Contraindications
Patients with:
 concomitant therapy with nephrotoxic or cytotoxic agents
 concomitant immunosuppressive or radiation (UVB and PUVA) therapy
 previous or concomitant malignancies
 infections of any type






primary or secondary immunodeficiency
severe organ dysfunction
drug or alcohol abuse
abnormal renal function
uncontrolled hypertension
poor compliance history
Dosimetry guidelines
Induction base
: The starting dose should be 3 to 4 mg/kg/body weight/day in one single dose or two divided doses.
If there is no improvement within one month the dose can be increased, but not exceeding 5
mg/kg/day.
Maintenance Phase : With good improvement the dose can be lowered in steps of 0.5 - 1 mg/kg to the minimum
maintenance dose, often 2.5 - 3 mg/kg/day. The duration of treatment should not be more than 2
years. Discontinue if there is poor response to CyA at doses of 5 mg/kg/day within 6 weeks.
In general, patients who go into remission with lower CyA doses eg. 2.5 mg/kg/day (good responders) have better control
whilst on maintenance. Those requiring higher induction doses, up to 5 mg/kg/day, (poorer responders) are more difficult
to maintain on lower maintenance doses.
Side Effects
The major adverse effects are nephrotoxicity, hypertension, second tumours, hyperlipidemia and the minor ones are
tremor, hypertrichosis, gingival hyperplasia and nausea.
Monitoring
The major adverse effects are nephrotoxicity, hypertension, second tumours, hyperlipidemia; and the minor ones are
tremor, hypertrichosis, gingival hyperplasia and nausea.
Baseline
 12-hour fasting creatinine (3 separate occasions)
 12-hour fasting lipids
 serum bilirubin
 liver enzymes
 serum potassium
 serum magnesium
 serum uric acid
 urinary protein
 Glomerular filtration rate (GFR)
- ideally this should be done as serum creatinine is an unreliable indicator of decreased renal function.
First 3 months: every 2 weeks
 serum creatinine
 blood pressure
Subsequently: monthly
 serum creatinine
 blood pressure
Periodically
 liver enzymes
 serum electrolytes, uric acid, lipids
If serum creatinine rises beyond 30% of baseline level, CyA dosage should be reduced for one month and continued if it
stays below this level, otherwise CyA should be discontinued. Present experience suggests that even dermatologic doses
of CyA can produce morphologic changes on renal biopsy and reduced GFR. These nephrotoxic effects are correlated
with dose and duration of therapy. Fortunately, the renal abnormalities are generally not progressive after CyA
withdrawal and are at least partially reversible although not in all cases.
If hypertension develops (diastolic > 95 mm) it should be treated with calcium antagonists such as nifedipine or isradipine
but not diltiazem or verapamil (interference with CyA blood) Diuretics should not be used. Withdraw CyA if
hypertension cannot be controlled with these measures.
Drug interactions with CyA
Care should be taken with the following medications:
Nephrotoxic drugs
- aminoglycosides, amphotericin B, ciprofloxacin, trimethoprim
Non-steroidal anti-inflammatory drugs - potentiates adverse effects on renal function.
Lovastatin and colchicines
- increased risk of muscular toxicity.
Agents increasing blood CyA levels
- ketoconazole, erythromycin, doxycycline, oral contraceptives, some calcium
channel blockers (diltiazem, nicardipine, verapamil)
Agents decreasing blood CyA levels - phenobarbitone, phenytoin, carbamazepine, rifampicin.
vi. Systemic Corticosteroids
Systemic corticosteroids are not used routinely because it may precipitate erythrodermic or generalised pustular psoriasis,
or very unstable psoriasis on withdrawal. Therefore it should only be used by dermatologists if absolutely necessary.
Indications
It is indicated only for these 3 rare and specific conditions:
 Persistent, or otherwise uncontrollable, erythrodenna causing metabolic complications.
 Generalised pustular psoriasis of Von Zumbusch type if other drugs are contraindicated or ineffective (including
impetigo gestationis - a form of pustular psoriasis in pregnancy).
 Hyperacute psoriatic polyarthritis that threatens irreversible joint damage.
Systemic corticosteroids are used for a short period only so as to allow the slower systemic drugs e.g. methotrexate or
retinoids started at the same time to work.
Dosage
Start with high dose oral steroids l mg/kg per day and tail off slowly.
Monitoring
Blood sugar, electrolytes
Blood pressure, peptic ulcer disease
Side Effects
This can be divided into 2 categories - those resulting from:
Withdrawal
 Acute adrenal insufficiency
 Pseudotumour cerebri with papilloedema - rare
 Precipitate pustular or erythrodermic psoriasis
And those from continued use of large doses
 Hypothalamic-pituitary-adrenal axis suppression
 Fluid and electrolyte disturbances - hypokalaemic alkalosis and oedema
 Hyperglycaemia and glycosuria
 Increased susceptibility to infections including tuberculosis and candidiasis
 Peptic ulcer
 Osteoporosis and vertebral compression fractures
 Proximal myopathy
 Behavioral disturbances - nervousness, insomnia, change in mood or psyche, manic-depressive psychosis or
schizophrenia
 Posterior subcapsular cataracts
 Cushing's syndrome
2.7.4 Combination Therapy
The rationale for combination therapy is to try to reduce the side effect profile of individual treatments and to improve
efficacy. Some examples of useful combination therapy are:
i. Retinoids + PUVA (RePUVA)
Reduces total UVA dose and number of treatments for clearance with lower risks of UVL-induced carcinogenesis.
ii. PUVA-UVB (ReUVB)
As with RePUVA, better clearance with fewer treatments and less cumulative UVB.
iii. Calcipotriol + PUVA (D-PUVA)
As above, less treatments and cumulative UVA dose for clearance.
iv. PUVA + Methotrexate
Rapid clearance possible even with recalcitrant disease.
v. Calcipotriol + UVB
No significant improvement seen in Kragballe's study although later as yet unpublished data suggests synergistic
effects as with RePUVA. Photosensitive reactions can occur.
vi. Calcipotriol + Cyclosporin A
Clearance in 50% of patients with very low dose cyclosporin (2 mg/kg/day) compared to 12% clearance with
cyclosporin 2 mg/kg/day alone.
2.8
AMBULATORY TREATMENT (DAY CARE)
2.8.1 Introduction
Ambulatory treatment centres provide specialized combination therapies such as Goeckerman and Ingram, in addition to
standard office treatments for psoriasis. Traditional treatment plans may vary depending on the individual centre and they
allow for extended periods of care under the supervision of a physician. The basic components of each treatment are
listed.
Approximately 20% of psoriasis patients require more than topical therapy to improve their skin. Phototherapy with UVB
or PUVA (Psoralens plus Ultraviolet A) is often the next recommended choice of treatment. Proper patient selection and
pre-treatment assessment, good dosimetry and protocol and regular monitoring will result in good therapeutic index.
2.8.2 UVB Phototherapy (Ultraviolet B Irradiation)
UVB is used in psoriasis usually in the Goeckerman or Ingram's Regimes, i.e. in combination with either coal tar or
anthralin. UVB alone is used regularly only in guttate psoriasis.
UVB wavelength is in sunburn range of 300 - 320 nm.
Goeckerman Regime
: Coal tar bath
UVB exposure (minimal erythemogenic doses)
Coal tar application
Ingram Regime
: Coal tar bath
UVB exposure (minimal erythemogenic doses)
Application of dithranol in Lassar's paste
Indication for Treatment
: 1. Failed topical treatment alone
2. Chronic stable plaque psoriasis
3. Guttate psoriasis
2.8.3 Photochemotherapy (PUVA)
 Photochemotherapy combines the photosensitising drug methoxsalen with Ultraviolet A Phototherapy (i.e wavelength
range of 320 - 400 nm)
 The drug is given in a dosage of 0.6 mg/kg of body weight, 2 hours before UVA exposure. UV protective eyeglasses
must be worn after ingestion of drug for 12 hours
 The dosage of UVA is determined by the patient's skin type (i.e. the sensitivity of the skin to UVA radiation) or
preferably by prior determination of the minimum phototoxic dose (MPD)
 Treatments are usually given 3 times weekly
 85% of patients go into remission after 20 - 30 treatments. Total duration of treatment may take about 6 - 10 weeks
 Relapse may occur within 6 to 12 months
 Maintenance treatment may be required for frequent relapses
Benefits of PUVA
- High likelihood of response
- Absence of need for topical except perhaps emollients
- Simplicity of therapeutic schedules
PUVA Contraindications
Absolute
Xeroderma pigmentosum
Gorlin's syndrome
Hereditary dysplastic naevus syndrome
Systemic lupus erythematosus
Dermatomyositis
Trichothiodysdrophy
Bloom's syndrome
Cockayne's syndrome
Previous malignant melanoma
Relative
Major
Age less than 10 years*
Previous or current non-melanoma skin cancer
Previous exposure to arsenic or ionizing radiation
Current premalignant skin lesions
Concomitant immunosuppressive therapy
Pregnancy
Porphyria
Minor
Age less than 16 years*
Cataracts +
Bullous pemphigoid
Pemphigus
Previous or concomitant treatment with methotrexate
Significant hepatic dysfunction +
Previous internal malignancy
* A lower age limit may be acceptable where topical psoralen is used
+ Oral psoralen only
Problems with PUVA
 Side effects
- short term (nausea, burning, dryness, pruritus)
- long term (increased risk of photodamage wrinkling, irregular pigmentation, lentigenes, benign
keratosis, premalignant keratosis and skin cancers)
 Inconvenience
- need to visit clinic 3 times/week
- need to wear UV protective eyeglasses for up to 12 hours after ingestion of psoralen
- must protect from further sun exposure during day of treatment.
Comments:
The therapeutic index of this treatment is high if the cumulative dose of UVA is less than that likely to cause skin cancer
or severe photodamage. As a general guide, it is recommended that one should receive not more than 200 treatments or
not more than 1000 – 1500 joules/cm2 cumulative dose of UVA.
A careful and permanent record of the total number of treatment sessions and cumulative UVA dosage is essential, and
supervision by dermatologists with special PUVA experience is desirable. In addition, annual review of patients, when
possible up to 10 years is advisable to check for premalignant and malignant skin cancers.
2.8.4. Combination Regimes with Phototherapy
 PUVA may be combined with concomittant use of retinoids and methotrexate
 PUVA may also be used in conjunction with topical agents such as calcipotriol and topical steroids
 The potential advantage includes reduction in number of PUVA sessions and/or cumulative UVA dosage and clearance
of psoriasis in patients unresponsive to PUVA alone. This may reduce the long term skin cancer risk of PUVA therapy
 Combination with retinoids may be considered in patients who have reached 50 treatment sessions or relapsed within 6
months of previous PUVA therapy
 Acitretin dosage of 0.25-0.5 mg/kg is recommended
 If associated prolonged risk of teratogenicity is unacceptable, isotretinoin may be substituted due to its shorter period
of teratogenicity risk upon cessation of treatment
 Retinoids may be started together with PUVA or one week prior to PUVA
 PUVA and methotrexate are effective but is recommended only for very severe psoriasis due to possibility of further
increasing skin cancer risk
 Concomittant use of topical steroids, although producing more rapid clearance is associated with earlier relapse
 PUVA and cyclosporin appear to confer little therapeutic advantage and skin cancer risk is likely to be potentiated
 PUVA and calcipotriol appears superior to PUVA. The duration of treatment, number of radiations and cumulative
UVA dose has been known to reduce
2.8.5 Hand and Foot PUVA
 Local PUVA using oral or topical psoralen delivery is a useful and effective second line treatment for hand and foot
psoriasis or palmoplantar psoriasis
2.8.6 Bath PUVA
Bath PUVA is effective and an increasingly popular alternative to oral PUVA.
Advantages include shorter irradiation time due to greater photosensitization, lack of GIT, nephrotoxic or other systemic
adverse effects.
Data concerning ocular risks with bath PUVA are still lacking, hence it is still recommended to wear eye protection for at
least 12 hours after treatment.
Requires closer patient supervision.
2.8.7 Summary of Systemic and Physical Therapy
Table II - Systemic, UVB/UVA Phototherapy, and Photochemotherapy (PUVA)
Phototherapy UVB
Photochemotherapy (PUVA)
Methotrexate
Hydroxyurea
Retinoids
Effectiveness
and Remission
+++
++++
++++
++
+++
Patient
Monitoring
++
++
+ I,II
++ II
+ II
Clinical
Indications
All forms G
All forms G
All forms
All forms
All forms
Comments
d,e,f,g
a,b,c,d,e,f
a,b,c,e
a,b,c,e
a,b,c,e
Effectiveness and Remission
:
+
++
+++
++++
Partial clearing
Partial clearing and short remission (1 month)
Total clearing and short remission (1 month)
Total clearing and long remission (months to years)
Patient Monitoring
(patient and laboratory)
:
+
++
I
II
weekly to monthly
monthly to every 6 months
Roenigk HH Jr, Auerbach R, Maibach HI, et al. Methotrexate in psoriasis;
revised guidelines, J Am Acad Dermatol 1988; 19: 145-56
Physicians’ Desk Reference – thorough familiarization needed
Clinical Indications
:
G
Reduce frequency when active, inflammatory phase is over
Comments
:
a.
b.
c.
d.
e.
f.
Should not be used in children except rare circumstances
Contraindicated in pregnant patients
Should be used with caution in female patients of childbearing potential
Recommended periodic evaluation for skin cancer
May be combined with other treatment modalities
Unsupervised UV light, including use of tanning booths is inappropriate.
Likewise home phototherapy should only be used with great caution under
the direction of the patient's physician. PUVA (Photochemotherapy) should
not be attempted in the home unless under direct physician supervision
UVB alone more effective than UVA alone
g.
2.8.8 Additional services may include the following:
a)
b)
c)
d)
Specialized scalp treatments
Nail treatment
Patient education sessions
Psychological support groups
2.9
HOSPITALIZATION (IN-PATIENT CARE)
2.9.1 Indications for hospitalization
Some patients may require inpatient treatment. The criteria for admission may include the following:
i.
Acute erythrodermic psoriasis
ii.
Acute generalised pustular psoriasis
iii. Hyperacute psoriatic polyarthritis that threatens irreversible joint damage
iv. Psoriasis not controlled with outpatient treatment
v.
Complications from previous treatment such as topical, systemic, phototherapy or photochemotheraphy, not
controlled with outpatient therapy
vi. Psoriasis that is physically or emotionally disabling enough to limit activities of daily living
2.9.2 Adjunctive Therapies
i.
Antihistamines/antibiotics
ii.
Occlusive dressings and/or suits
iii. Wet dressings
iv. Antifungal creams/antibacterial creams
v.
Specialized baths
vi. Psychiatric counselling
vii. Others
3. PATIENT EDUCATION
This is an important part of any treatment plan and should include information on the disease and the effects that
trauma, alcohol, infection and stress may have on psoriasis. Expectations of the results of therapy and interactions
that are possible between phototherapy and drugs and the disease are to be considered part of patient education. It is
very important for patients to be partners in treatment. At diagnosis the following should be provided:
i.
ii.
iii.
Booklet on psoriasis
Counselling to patients and or relatives
Patient taught on side effects, possible provoking factors and warned on harmful treatments e.g. colonic washout.
4. USE OF GUIDELINES TO DERIVE AUDIT MEASURES
Diagnosis, assessment and initial management
(1)
Is the diagnosis in clinical doubt?
(2)
Is the patient receiving any treatment likely to precipitate or aggravate psoriasis?
(3)
What in the patient's view is the most distressing or disabling aspect of psoriasis?
(4)
Has the nature of psoriasis been explained to the patient?
(5)
Have the treatment options been discussed in the light of (4)?
(6)
Has the patient had an adequately documented 8 - 12 week trial of topical treatment?
(7)
If topical steroids are included in the regimen is the potency and quantity used appropriate?
(8)
Is referral to a consultant dermatologist appropriate?
Phototherapy
(9)
Has the minimal erythema dose been estimated?
(10) Is the patient receiving an appropriate treatment regimen?
Systemic treatment
(11) Are the indications to move to systemic treatment appropriate?
(12) Have the options and side effects of possible regimens been fully discussed with the patient?
(13) If appropriate, has the need for contraception been fully discussed and appropriate provision
arranged if required?
(14) Has the patient been given a psoriasis systemic treatment card?
(15) If yes, does the patient show this card to the general practitioner when receiving prescriptions
for unrelated problems?
Photochemotherapy (PUVA)
(16) Has the patient been given advice about appropriate eye protection?
(17) Have men been given advice about screening genitalia during PUVA?
(18) Has the minimal phototoxic dose been estimated?
(19) Is there a clear record of individual treatment and cumulative Ultraviolet A dosage?
(20) Is the patient receiving an appropriate review and follow up programme?
Methotrexate
(21) Have pretreatment investigations excluded haemotological, biochemical and hepatic
contraindications?
(22) Is the patient taking any drug known to have an adverse interaction with methotrexate?
(23) Are the arrangements for regular review and haemotological and biochemical monitoring
appropriate?
Yes/No
Yes(What)/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Yes/No
Acitretin
(24) For women has the need for prolonged contraception (two years) after withdrawal of drug
been fully discussed?
(25) Is the dosage regimen appropriate?
(26) Are review arrangements adequate?
Yes/No
Yes/No
Yes/No
Cyclosporin
(27) Has the serum creatinine concentration been measured?
(28) Have potential drug interactions been considered?
(29) Is the current dose of cyclosporin appropriate?
Yes/No
Yes/No
Yes/No
5. SUPPORTING EVIDENCE
Refer to list of references
6. DISCLAIMER
Adherence to these guidelines will not ensure successful treatment in every situation. Further, these guidelines should not be
deemed inclusive of all proper methods of care or exclusive of other methods of care reasonably directed to obtaining the same
results. The ultimate judgement regarding the propriety of any specific procedure must be made by the physician in the light of
all the circumstances presented by the individual patient.
Other modalities of treatment used by patients such as traditional medicaments, herbs and nutritional supplements lack concrete
scientific proof of their effectiveness.
7. LIST OF REFERENCES
GENERAL
1.
2.
3.
4.
5.
REA Williams. Guidelines for management of patients with psoriasis. Regular review. Br Med J 1991; 303, 829-835.
Louise S Goodman & Alfred Gilman. The Pharmacological Basis of Therapeutics 1990; 8th edition, 1431-1462.
Treatment of Psoriasis. New England Journal of Medicine 1995; 332(9): 582-588.
British Photodermatology Group Guidelines for PUVA. Br J Dermatology (1994); 130, 246-255.
Guidelines of care for psoriasis. Journal of the American Academy of Dermatology (1993); 28: 632-7
TOPICAL AND INTRALESIONAL THERAPY
Tar
1.
2.
3.
4.
5.
6.
7.
8.
Chapman RS, Finn OA, An assessment of high and low temperature tars in psoriasis. Br J Dermatol 1976: 94: 71-4.
Finlay AY, Young DW. Short contact coal tar therapy for psoriasis. Clin Exp Dermatol 1985; 10: 371-4.
Lavker RN, Grove GL, Kligman Am. The atrophogenic effect of crude coal tar on human epidermis. Br J Dermatol 1981;
105: 77-82.
Lin AN, Moses K Tar revisited. Int J Dermatol 1985: 24: 216-8.
Lowe NJ, Wortzman MS, Breeding J, et al. Coal tar phototheraphy for psoriasis reevaluated: erythemogenic versus
suberythemogenic ultraviolet with tar extract in oil and crude coal tar. J Am Acad Dermatol 1983; 8: 781-9.
Petrozzi JW, Barton JO, Kaidbey KH, et al. Updating the Goeckerman regimen for psoriasis. Br J Dermatol 1978; 98:
437-44.
Stern RS, Gange RW, Parrish JA, et al. Contribution of topical tar oil to ultraviolet B phototherapy for psoriasis. J Am
Acad Dermatol 1986; 14: 742-7.
Young E. The external treatment of psoriasis: a controlled investigation of the effects of coal tar. Br J Dermatol 1970; 82:
510-5.
Anthralin
1.
Abel EA, O'Connel BM, Farber EM. Psoriasis day care centre at Stanford: part-time and full-time programmes. Int J
Dermatol 1987; 26: 500-7.
2.
Ashton RE, Andre P, Lowe NJ, et al. Anthralin: historical and current perspectives. J Am Acad Dermatol 1983; 9: 17392.
3.
Ingram JT. The approach to psoriasis. Br Med J 1953; 591-4.
4.
Lowe NJ, Ashton RE, Koudsi H, et al, Anthralin for psoriasis: short-contact anthralin therapy compared with topical
steroids and conventional anthralin. J Am Acad Dermatol 1984; 10: 69-72.
5.
Ryatt KS, Statham BN, Rowell NR. Short-contact modification of the Ingram regimen. Br J Dermatol 1984; 111: 455-9.
Calcipotriol
1.
Murdoch D et al. Calcipotriol - A Review of its Pharmacological Properties and Therapeutic Use in Psoriasis Vulgaris
2.
Jones JB et al. A multi-centre, parallel-group comparison of calcipotriol ointment and short-contact dithranol therapy in
chronic plaque psoriasis. Br J Dermatol (1992), 127, 266-271
3.
Cork M. Economic considerations in the treatment of psoriasis. Dermatol Pract 1993; 1(3): 16-20
4.
Tham SN et al. A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis. Br J Dermatol 1994;
131, 673-677
5.
Frappaz A et al. Calcipotriol in combination with PUVA: A randomised double blind placebo study in severe psoriasis.
Eur J Dermatol 1993; 3: 351-4
6.
Speight EL et al. Calcipotriol improves the response of psoriasis to PUVA. Br J Dermatol 1993; Suppl 42: 32-33
7.
Poyner T et al. Long-term treatment of chronic plaque psoriasis with calcipotriol. Journal of Dermatological Treatment
(1993), 4: 173-177
8.
Ramsay CA et al. Long-term use of topical calcipotriol in chronic plaque psoriasis. Dermatology (1994), 189: 260-264
9.
Highton A et al. Calcipotriene ointment 0.005% for psoriasis: A safety and efficacy study. J Am Acad Dermatol 1995; 32:
67-72
10.
Grossman RM et al. A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose
cyclosporine: Results of a multi-centre placebo controlled study. J Am Acad Dermatol 1994; 31: 68-74
11.
Kragballe K, Gjersten BT, De Hoop D, Karlsmark T, Van De Kerkhof PCM, et al. Double-blind, right/left comparison of
calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 337: 193-196.
12.
Cunliffe WJ, Berth-Jones J, Claudy A et al. Comparative study of calcipotriol (MC 903) ointment and betamethasone 17valerate ointment in patients with psoriasis vulgaris. J Am Acad Dermatol 1992; 26: 736-43.
Keratolytics
1.
Davies MG, Briffa DV, Greeves MW. Systemic toxicity from topically applied salicylic acid. Br Med J 1979; 1: 661.
2.
Going SM, Guyer BM, Jarvie DR, et al. Salicylic acid gel for scalp psoriasis. Clin Exp Dermatol 1986; 11: 260-2.
3.
Goldsmith LA. Salicylic acid. Int J Dermatol 1979; 18: 32-6.
4.
Hulsebosch HJ, Ponec-Waelsch M. The interaction of anthralin, salicylic acid and zinc oxide in pasters. Dermatologica
1972; 144: 287-93.
5.
Van Scott EJ, Yu RJ. Alpha hydroxy acids: procedures for use in clinical practice. Cutis 1989; 43: 222-8.
6.
Van Scott EJ, Yu RJ. Control of keratinization with L-hydroxy acid and related compounds. Arch Dermatol 1974; 110:
586-90.
Topical and Intralesional Corticosteroids
1.
Abell E. Treatment of psoriatic nail dystrophy. Br J Dermatol 1972; 86: 79-82.
2.
3.
4.
5.
6.
7.
du Vivier A, Stoughton RB. Tachyphylaxis to the action of topically applied corticosteroids. Arch Dermatol 1975; 111:
581-3.
Katz HI, Hien HT, Prawer SE, et al. Superpotent topical steroid treatment of psoriasis vulgaris: clinical efficacy and
adrenal function. J Am Acad Dermatol 1987; 16: 804-11.
Lee SS. Topical steroids (review). Int J Dermatol 1981; 20: 632-41.
Nilsson JE, Gip LJ. Systemic effects of local treatment with high doses of corticosteroids in psoriatics. Acta Derm
Venereol (Stockh) 1979; 59: 245-8.
Tan PL, Barnett GL, Flowers FP, et al. Current topical corticosteroid preparations. J Am Acad Dermatol 1986; 14: 79-93.
Vickers CFH. Topical corticosteroids. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al, eds. Dermatology in general
medicine. 3rd Edition, New York: Mcgraw-Hill, 1987: 2540-5.
SYSTEMIC THERAPY
Methotrexate
1.
Ashton RE, Millward - Sadler GH, White JE. Complications in methotrexate treatment of psoriasis with particular
reference to liver fibrosis. J Invest Dermatol 1982; 79: 229-32.
2.
Dahl MGC. Methotrexate and the liver. Br J Dermatol 1969; 81: 465-7.
3.
Hanno R, Gruber GG, Owen LG, et al. Methotrexate in psoriasis. J Am Acad Dermatol 1980; 2: 171-4.
4.
Jolivet J, Cowan KH, Curt GA, et al. The pharmacology and clinical use of methotrexate. N Eng J Med 1983; 309: 1094104.
5.
Reese LT, Grisham JW, Aach RD, et al. Effects of methotrexate on the liver in psoriasis. J Invest Dermatol 1974; 62:
597-602.
6.
Roenigk HH, Auerbach R, Maibach HI, et al. Methotrexate in psoriasis: revised guidelines. J Am Acad Dermatol 1988;
19: 145-56.
7.
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Retinoids
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Salazopyrine/Sulphasalazine
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Hydroxyurea
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Cyclosporin
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Systemic Corticosteroids
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Antimicrobials
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PHYSICAL THERAPY
UVB Phototherapy
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Combination Treatment
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Hospitalisation and Day Care
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