TREATMENT

Various forms of treatment have been developed in the past several decades. They
have mostly been developed
empirically, and as with all other diseases of unknown cause, new regimens are being
tried constantly. Recently,
biotechnology has allowed the development of monoclonal antibodies and fusion
proteins targeting single epitopes or
compounds with relevance in the psoriatic tissue reaction. Furthermore, the
experimental administration of recombinant
cytokines such as IL-10 showed beneficial effects at least in a subgroup of psoriasis
patients. These new-generation
therapies will gain importance in the routine treatment of psoriasis in the near future.
There is debate as to whether the aim of any psoriasis therapy should be total clearing
of the lesions. Under many
circumstances, patients may regard the successful clearing of scaling a sufficient
therapeutic response; however, when
lesions are present in visible areas such as the hands, complete resolution is
necessary. 47 Complete clearing normally
needs a much higher therapeutic effort, in particular when patients present with severe,
frequently relapsing psoriasis. In
these pateints, discussion about the therapeutic goal between dermatologist and patient
should define the individual
treatment strategy.
Topical Treatment (See also Chap. 244 and Chap. 251)
ANTHRALIN Anthralin (1,8-dihydroxyanthrone; cignolin, dithranol) was introduced by
Galewsky and Unna in 1916. This
compound is still a widely used remedy for psoriasis in different vehicles and application
modes. A major advantage of
anthralin is the lack of any long-term side effects, which allows unlimited reintroduction
of the drug as long as therapy is
required.
Mode of action Anthralin possesses antiproliferative activity on human keratinocytes. In
recent years it has become
clear that this compound also exerts strong anti-inflammatory effects mainly on cells of
the inflammatory infiltrate.
Inhibition of neutrophil and monocyte functions and production and ?-oxidation of
leukotriene B 4 from neutrophils have
been observed. It was found recently that anthralin induces nuclear transcription factor
NF-? B in murine keratinocytes. 48
Since NF-?B is involved in the transcription of proinflammatory cytokines such as IL-6,
IL-8, and TNF-a, these findings
may be helpful in explaining the irritant properties of anthralin.
Clinical use Chronic plaque-type psoriasis responds best to anthralin treatment. Guttate
psoriasis also can be treated
effectively. Classic anthralin therapy starts with low concentrations (0.050.1%)
incorporated in petrolatum or zinc paste

and given once daily. To prevent autooxidation, salicylic acid (12%) should be added.
The concentration is increased
weekly in individually adjusted increments up to about 5% until the lesions resolve.
Short-contact treatment is an
alternative mode of application. Higher concentrations of anthralin (15%) in watersoluble vehicles are applied to the
lesions for a short period of time (usually 1020 min) and thereafter washed off.
Application time is increased weekly until
the lesions have cleared. A new galenical formulation (Micanol) reduces local irritation
and staining of skin and
equipment. A leukoderma-like zone (pseudoleukoderma) may become visible at the
site of treated lesions.
Adverse events Anthralin can cause irritant reactions (anthralin dermatitis) in
susceptible patients or after increasing
the concentration too fast. Since anthralin can stain the hair a purple to greenish color,
scalp psoriasis should be treated
only with great caution. At higher concentrations, anthralin causes brownish
discoloration of the surrounding skin
(anthralin-brown) and of clothing that comes into contact with the compound. Since
these oxidation products remain at
the upper levels of the stratum corneum, discoloration disappears within days after
stopping anthralin application.
Removal of stains from clothing, however, is difficult or impossible.
VITAMIN D 3 AND ANALOGUES Since the first report about the beneficial effects of
vitamin D 3 in psoriasis by Morimoto
et al., 49 new analogues have been developed to decrease hormonal effects on
calcium/phosphate homeostasis and to
maintain effects on keratinocyte proliferation and differentiation. Soon after the
introduction of the first vitamin D 3
analogue, calcipotriol (also called calcipotriene in some countries), to topical therapy, it
became a widely used remedy for
plaque-type psoriasis. 50 Another vitamin D 3 analogue, tacalcitol, is available in some
countries. 51Recently, active
hormone 1,25-dihydroxyvitamin D 3 (calcitriol) was registered for topical psoriasis
treatment in a number of countries. 52
Mode of action Vitamin D 3 and its analogues inhibit keratinocyte proliferation and
induce terminal differentiation. 53
Anti-inflammatory properties of these compounds include inhibition of nuclear factor
NF-?B protein in lymphocytes,
leading to a reduced transcription of IL-2. 54 Calcitriol and calcipotriol can inhibit
production of IL-6 from
cytokine-stimulated human dermal microvascular endothelial cells and reduce the
antigen-presenting function of
Langerhans cells. Calcitriol is a potent inhibitor of dendritic cell differentiation. 55
Clinical use Calcitriol, calcipotriol, and tacalcitol are used for plaque-type psoriasis twice
or once daily, respectively.

Treatment is limited by the area of application and time due to possible effects on
calcium/phosphate homeostasis.
Calcipotriol is inactivated by salicylic acid; therefore, lesions should not be pretreated
with this compound. When
calcipotriol is used in combination with ultraviolet (UV) light, application should follow
light exposure because of the
UV-absorbing properties of calcipotriol.
Adverse effects Local irritation may occur at the beginning of treatment. Some patients
develop facial rashes after
application of calcipotriol elsewhere on the body. Changes in calcium and/or phosphate
metabolism are rare when
application follows the respective guidelines.Calcipotriol has been found to be a safe
treatment for children with
psoriasis. 56
TAZAROTENE Tazarotene is a retinoid for topical use that reduces mainly scaling and
plaque thickness, with limited
effectiveness on erythema. In comparison with other topical drugs for psoriasis,
tazarotene has a lower efficacy.
However, efficacy can be enhanced by combination with UVB therapy. 57
TAR The use of tar either as coal tar or wood tar (birch, pine, beech) has a long history
in antipsoriatic therapy. These
tars contain a great variety of compounds, most of which are not well defined. Very little
is known about how tars act in
skin. Preparations of 2% to 5% tar in various bases have been shown to be
preferentially effective in chronic plaque-type
psoriasis. These preparations are nonirritant, and serious side effects are not seen even
after long periods of treatment.
TOPICAL GLUCOCORTICOIDS Topical glucocorticoids can be used effectively in
psoriasis. They are discussed in
detail in Chap. 243.
BLAND EMOLLIENTS Between treatment periods, skin care with bland emollients
should be performed in order to avoid
dryness, leading to early recurrence, and to prolong therapy-free intervals. The addition
of urea (up to 10%) is helpful to
improve hydration of the skin and remove scaling of early lesions.
Treatment with Ultraviolet Light
PHOTOCHEMOTHERAPY (PUVA) (See Chap. 266) The use of systemic psoralens
plus ultraviolet A (PUVA) to treat
psoriasis was introduced in 1974 by Parrish and coworkers. 58The effectiveness of
PUVA in clearing psoriasis has now
been widely documented and confirmed by cooperative clinical studies in the United
States and in Europe. 59 Treatment
consists of oral ingestion of a potent photosensitizer such as 8-methoxypsoralen (8MOP) or trimethoxypsoralen at a
constant dose (0.60.8 mg/kg) and variable doses of UVA, depending on the sensitivity
of the patient. Approximately 2 h

after ingestion of the psoralen, UVA is started, usually at a dose of 1 J/cm 2, adjusting
upward for skin type. The UVA
dose is increased by suberythematous amounts, generally ranging from 0.5 to 1.5 J/cm
2. The dose of UVA for a given
treatment should not lead to brisk erythema. Treatments are performed two or three
times a week or, under a more
intensive protocol, four times a week. In most patients, clearing occurs after 19 to 25
treatments, and the amount of UVA
needed ranges from 100 to 245 J/cm 2. PUVA results in rapid pigmentation of the skin,
making it necessary to increase
the dosages of light. Overdosage results in a sunburn type of reaction, which
characteristically is more delayed than that
seen with UVB; i.e., it occurs 24 to 48 h after treatment. Administration of lower doses of
psoralen or UVA, as well as
prolonged treatment courses, may demonstrate psoriasis that is nonresponsive and
may even result in relapses in
patients under treatment. Psoralens such as 8-MOP intercalate with DNA. With the
energy of UVA, psoralens covalently
cross-link nucleic acids between opposing strands of duplex regions of DNA. The
formation of these cross-linking
bifunctional photoadducts leads to irreversible photoinhibition of DNA synthesis and
mitosis. 60 This reaction is thought to
be important in the hyperproliferative psoriatic epidermis. Because demonstration of
interstrand cross-links in treated
human epidermis has yet to be shown, mechanisms other than DNA binding need to be
considered. Since PUVA was
shown to be therapeutically effective in a variety of dermatoses, some of which are not
related to hyperproliferation, more
than one mode of action appears to be likely. Side effects and the consequences of
overdosage include nausea,
dizziness, and headache. Approximately 95 percent of the drug is excreted via the
kidneys within 8 h. During this time,
cutaneous sensitivity to UV light is increased considerably. Measures for sun protection
must be taken during the 8 to 12
h after ingestion of the psoralen. To protect the eyes, UVA-blocking plastic wraparound
glasses should be worn outdoors
for the 24 h after ingesting psoralen. Indoors, especially in a bright fluorescent light, the
same type of protective eyewear
is recommended. The psoralen molecule reaches highest concentrations in skin within 2
to 3 h after oral ingestion; the
concentration slowly decreases during the following 8 h. During the entire day of
treatment, exposure to sunlight should
be avoided by wearing protective clothing and taking other appropriate precautions.
Since psoralens are found in the
lens, ophthalmologic examinations should be performed at yearly intervals. Long-term
side effects are of considerable

importance and make it necessary to restrict PUVA to patients with widespread and
severe psoriasis. A major early side
effect is pruritus, which usually can be managed by the topical use of emollients or lowpotency glucocorticoids. Late
sequelae include the spectrum of long-term actinic skin damage, e.g., solar elastosis,
dry and wrinkled skin, and hyperand
hypopigmentation. PUVA freckles, which may persist for years, represent the potential
for the development of skin
cancers. Stern et al. 26 analyzed 13,800 patients who had been receiving PUVA
therapy and had been followed up for 5.7
years; in this group there was a dose-related increased frequency of squamous cell
carcinomas. 26 Patients who have
received relatively high dosages of PUVA had a 12.8 times higher incidence of genital
squamous cell carcinomas than
patients exposed to lower dosages of PUVA. This finding was independent of skin
pigmentation, prior tar therapy, or prior
x-irradiation. 26Malignant melanoma risk increases especially in those with more than
250 treatments. 61
BATH PUVA Another way to deliver the photosensitizer (8-MOP or 5-MOP) to the skin is
by addition of these compounds
to bath water, first described by Fischer and Alsins in 1976. 62 Major advantages of
bath PUVA are the lack of systemic
effects, such as gastrointestinal complaints (nausea is present in about 13 percent of
patients taking 8-MOP orally), and
the overall reduction of UV dose down to one-quarter of that required to obtain
therapeutic results similar to those of
conventional PUVA, thus reducing the risk of nonmelanoma skin cancer. 63
Furthermore, erythema is less frequent in
bath PUVA patients, and eye protection by sunglasses is not required. Experimental
studies have shown that bath PUVA
reduces keratinocyte proliferation and suppresses activation of lesional T cells. To
reduce the cost of the larger amounts
of liquid 8-MOP required when using bath PUVA in a tub (volume of 150200 L), the
employment of a polyethylene sheet
bath has been proposed and has been shown to achieve therapeutic results similar to
those conventional bathing in a
large volume. 64
BALNEOPHOTOTHERAPY Empirically, it has been known that the combination of saltwater bathing and sunlight
exposure is an effective treatment for psoriasis. From studies at the Dead Sea, it
became clear that highly concentrated
salt water (>20%) together with UVB light is most effective. 65This therapeutic strategy
also was termed
balneophototherapy; it has become increasingly popular in Europe, where concentrated
salt-water baths together with

artificial UVB sources are used in psoriasis treatment centers. A possible mechanism of
concentrated salt-water bathing
is the elution of biologically active peptide mediators and enzymes such as human
leukocyte elastase from the inflamed
skin.
SELECTIVE UVB THERAPY Treatment with UVB without UVA, also known as selective
UVB phototherapy (SUP), can
be performed as monotherapy or preferably in combination with topical treatments such
as glucocorticoids, vitamin D 3
and analogues, tazarotene, or anthralin. SUP is very effective in guttate psoriasis and
also improves lesions of the
plaque type. Today, narrow-band UVB treatment (311 nm, Philips TL01 bulbs) has
become a standard therapy for
plaque-type and guttate psoriasis. Several new aspects of UVB action on the skin have
been elucidated. These include
depletion of Langerhans cells, decreased leukocyte adhesion to the microvasculature,
depletion of intraepidermal T cells,
and induction of IL-10 production from macrophages, which acts as an antiinflammatory mediator.
Systemic Treatment
Systemic treatment of psoriasis is required in cases of severe disease when lesions are
widespread or pustular or when
psoriasis is in an active phase, with rapid flare-ups after topical courses including UV
light. Systemic treatment should be
monitored carefully.
METHOTREXATE (See Chap. 256) Methotrexate (MTX) was introduced as an
antipsoriatic agent in 1958. It is a widely
used systemic regimen for severe forms of psoriasis and most beneficial in pustular
forms of the disease. MTX is the
drug of choice for severe psoriatic arthritis.
Mechanism of action MTX inhibits DNA synthesis (S phase of the cell cycle) by
competing as a substrate for
dihydrofolate reductase; originally, it was thought to act primarily on the rapidly dividing
basal keratinocytes of the
psoriatic lesion. The group of Weinstein 66 demonstrated that proliferating lymphoid
cells in psoriatic lesions are over
1000 times more sensitive to the cytotoxic effects of MTX than primary human
keratinocytes. It also has been shown that
MTX exerts anti-inflammatory effects mediated through intracellular accumulation of 5aminoimidazole-4-carboxyamide
ribonucleotide (AICAR), thereby increasing the release of adenosine. Adenosine exerts
anti-inflammatory effects mainly
on neutrophils, where an inhibition of adhesion and reactive oxygen intermediate
production has been demonstrated.
New data suggest that MTX induces apoptosis in activated T cells and keratinocytes. 67
, 68

Clinical use Pustular psoriasis and psoriatic arthritis are treated most effectively with
MTX. In psoriasis vulgaris of the
chronic plaque type, MTX monotherapy is less efficacious and should be combined with
topical compounds to achieve
clearing of the lesions.
Dosage The usual dosage of MTX is between 10 and 25 mg once a week. The
preferred mode of delivery is intravenous
or intramuscular in order to obtain best efficacy and to control treatment. MTX can also
be given orally using a dosing
schedule in which 5 mg is given every 12 h over a 36-h period. This regimen may be as
effective as treatment with a
once-weekly parenteral dose.
Adverse effects Most commonly nausea, anorexia, fatigue, headaches, and alopecia
are encountered as adverse
effects. Development of leukopenia and thrombocytopenia indicates serious dysfunction
of the bone marrow and may be
a sign of MTX overdose. In this case, a folinic acid rescue (25 mg of leucovorin
intramuscularly) should be performed,
preferably within the first 4 h. In case of renal dysfunction, leucovorin is given repeatedly
until renal function improves.
Since MTX is excreted mainly via the kidneys, patients with a history of kidney
dysfunction should not be treated with
MTX so as to avoid increased kidney toxicity. A rare but life-threatening side effect of
MTX therapy is acute interstitial
pneumonitis, which is believed to be a result of a hypersensitivity reaction. Interestingly,
in contrast to rheumatoid
arthritis therapy, there are only very few reports of pneumonitis in psoriasis patients
treated with MTX. Lethality is about
15 percent in rheumatoid arthritis patients treated with the same doses of MTX as are
used for psoriasis. Hepatotoxicity
is a major concern with MTX treatment. Patients with a history of liver disease or alcohol
abuse must be excluded. The
risk of developing liver fibrosis or cirrhosis increases with the overall cumulative MTX
dose. Above a cumulative MTX
dose of 1.5 g, monitoring of structural liver changes is mandatory.
Control of MTX therapy Routine measurement of hematologic parameters, as well as
liver and kidney function, should
be performed in MTX-treated patients. A recent study indicates that serial measurement
of type III procollagen
aminopeptide (PIIINP) is of value in detecting liver damage and may reduce the need
for liver biopsy in MTX-treated
patients. 69 On the other hand, comparisons of susceptibility to the development of
structural liver changes in patients
with rheumatoid arthritis and psoriasis reveal a higher risk in psoriasis patients for
reasons yet unknown. 70The

dermatologic guidelines for the use of MTX therefore still recommend liver biopsy after a
cumulative dose of 1.5 g and
thereafter at 1- to 1.5-g intervals. 71
CYCLOSPORINE (See Chap. 262) Cyclosporine is a cyclic polypeptide that is used
widely for the prevention of graft
rejection. It is accepted for the treatment of severe psoriasis in many countries.
Mode of action After penetration into the cell by a putative receptor, cyclosporine binds
to cyclophilin, a member of the
immunophilin group. The cyclosporine-cyclophilin complex binds to the phosphatase
calcineurin, thereby blocking its
ability to dephosphorylate the cytosolic component of transcription factor NF-AT (nuclear
factor of activated T cells). This
results in an impaired translocation of the NF-AT component to the nucleus. The nuclear
component of NF-AT is required
for functional activity to enhance transcription of the IL-2 gene. 72 Other pharmacologic
effects of cyclosporine with
possible relevance for psoriasis are an inhibition of the antigen-presenting capacity of
Langerhans cells and mast cell
functions such as degranulation and cytokine production.
Clinical use Multicenter studies have shown that cyclosporine is effective in about 70
percent of patients with severe
chronic plaque-type psoriasis when a low-dose regimen (<5 mg/kg per day) is used.
Clearing requires several weeks of
therapy, which can be maintained continuously. 73Improvement of nail changes as well
as of associated psoriatic arthritis
can be seen during long-term therapy. Cyclosporine therapy can be recommended as a
short-term intermittent regimen in
which the drug is tapered off as soon as major improvement is seen or as long-term
continuous treatment in recalcitrant
cases. Cyclosporine is also effective in erythrodermic as well as generalized pustular
psoriasis. Despite several attempts
to develop ointment formulations, cyclosporine is without effect when used topically.
Dosage The recommended dosage of cyclosporinearrived at as a result of multicenter
studies and consensus
meetingsis to start with 2.5 to 3 mg/kg per day divided into two daily doses. This can
be increased up to a maximum of
5 mg/kg per day. After clinical response is achieved, the cyclosporine dose can be
lowered to the best level for the
individual patient.
Adverse effects Among the side effects of cyclosporine, which are dose-related, is
impairment of kidney function, which
is largely reversible after drug withdrawal; also, hypertension may develop. A rise in
serum cholesterol and triglycerides
also has been observed. Clinically, hypertrichosis, gingival hyperplasia, tremor, and
fatigue may occur. Recent

investigations showed that long-term cyclosporine treatment increase the risk for
development of skin cancer. This risk is
particularly high in patients with a history of PUVA therapy using high doses of UVA. 74
Control of cyclosporine treatment Control of cyclosporine therapy includes blood
pressure measurement and
determination of serum creatinine as the most useful parameters for detecting
decreased kidney function in clinical
practice. If serum creatinine levels rise above 30 percent of individual baseline, the dose
of cyclosporine must be
reduced. In case of persistently enhanced creatinine values, the drug must be
withdrawn. Dermatologic examination is
necessary in order to early detect skin malignancies.
RETINOIDS (See Chap. 257) Acitretin, a derivative of vitamin A, is used mainly for the
treatment of psoriasis. Best
clinical results have been obtained in pustular forms of psoriasis. Acitretin has replaced
formerly used etretinate. The
half-life of etretinate is about 100 days and that of acitretin 2 to 3 days. When acitretin
was introduced, this short half-life
was thought to overcome long-lasting accumulation in the tissues, which meant severe
restrictions in the use of etretinate
in women due to the risk of teratogenic effects. However, it turned out that a portion of
acitretin is reesterified in vivo into
iso-acitretin and etretinate. 75 Therefore, restrictions on the use of acitretin in women of
childbearing age remain the same
as for etretinate.
Mechanism of action Retinoids regulate growth and terminal differentiation of
keratinocytes, thereby normalizing the
hyperproliferative state in psoriasis. After passing the cell membrane, retinoids form
complexes with cytosolic binding
proteins, which, after translocation into the nucleus, regulate gene transcription through
nuclear response elements.
Retinoids also exert some anti-inflammatory effects, such as inhibition of neutrophil
functions.
Clinical use Etretinate and acitretin are clinically effective in pustular forms of psoriasis,
including generalized pustular
psoriasis and PPP. For plaque-type psoriasis, retinoids show lower response rates than
other systemic modalities. In
combination with PUVA (Re-PUVA), retinoids can improve the clinical effectiveness of
acitretin in some cases. After
prolonged therapy, retinoids may lead to an improvement in psoriatic arthritis.
Dosage In severe psoriasis vulgaris and psoriatic erythroderma, acitretin is given in a
dose of 0.3 to 0.5 mg/kg per day
initially, which is increased at 3- to 4-week intervals to 0.75 mg/kg per day. To achieve
improvement, treatment over 3 to
4 months is necessary. Pustular psoriasis requires an initial dose of 1 mg/kg per day of
acitretin, which is given until

clinical improvement is seen. Thereafter, the dose is lowered gradually to a

maintenance dose of about 0.5 mg/kg per
day, which is given for 3 to 4 months.
Adverse effects The side effects of etretinate/acitretin therapy are dose-related. The
most prominent symptoms are
cheilitis, sicca symptoms of the eyes and mouth, generalized pruritus, dryness of the
skin, and loss of the stratum
corneum of palms and soles, leading to soreness in these areas. There may be
considerable hair loss during treatment
with acitretin. Muscle and joint pain as well as gastrointestinal complaints also may be
present. An elevation of serum
lipids is seen frequently during systemic retinoid treatment, especially in patients with a
history of lipid abnormality,
obesity, diabetes, smoking, and/or alcohol abuse. Elevations in liver enzymes (SGOT,
SGPT, LDH) may occur. A major
concern with the use of systemic retinoids is their high teratogenic potential. Since
acitretin is remetabolized into
long-lived compounds, use of this drug should be restricted to men and to women with
no childbearing potential. If
acitretin is given to women of childbearing age, strict contraception is required for the
time of therapy and for an
additional 2 years after drug withdrawal.
Control of retinoid treatment Liver and kidney function, blood glucose, and serum lipids
should be monitored initially at
3-week intervals and later every 2 months. Symptomatic treatment for dry skin, mouth,
and eyes should be given.
FUMARIC ACID ESTERS A mixture of fumaric acid monoethyl and dimethyl esters is
approved in Germany for systemic
treatment of severe psoriasis. Clinical experience exists since 1959 when fuamrates
were introduced.
Mode of action Inhibition of TNF-ainduced keratinocyte ICAM-1 expression by
dimethylfumarate has been
demonstrated. Monomethylfumarate, the main metabolite of dimethylfumarate, was
shown to stimulate release of T H2
cytokines IL-4 and IL-5 from human peripheral blood T cells without changing
production of T H1 cytokines IL-2 and
interferon-?. 76 Dimethylfumarate potently inhibits dendritic cell differentiation. 77
Recently, dimethylfumarate was shown
to induce apoptosis is a number of cells, including dendritic cells. 77 Furthermore, this
compound inhibits cytokine
production by blocking NF?B signaling. 78 , 79
Clinical use Fumaric acid esters are used for the treatment of severe psoriasis vulgaris.
80 Multicenter studies have
shown that about 70 percent of psoriasis patients respond to therapy. 81 There are
reports of long-term use of fumarates,

which seems to be possible in patients with recalcitrant psoriasis. Experience with

fumarates for the treatment of
erythrodermic and pustular psoriasis as well as psoriatic arthritis is very limited.
Adverse effects The most frequently observed adverse effects with fumaric acid ester
therapy for psoriasis are
gastrointestinal complaints and flush. Symptoms of the first can vary from nausea to
severe diarrhea; they are
dose-dependent and sometimes limit the use of the drug. Flush is seen in many
different forms from rashes and classical
flush to headache-like symptoms that occur irregularly for short periods. Leukocytopenia
and lymphopenia frequently are
associated with fumarate therapy. There also may be an increase of eosinophils. In rare
cases, impairment of renal
function has been observed.
Dosage Fumaric acid ester therapy follows a dosing schedule that begins with a lowstrength formulation and is
increased weekly for 3 weeks. Then therapy continues with a normal-strength
formulation that is increased weekly up to a
maximum of 1.29 g/day. Dosage is usually adjusted to an individual level, which can be
low in susceptible patients.
Control of fumarate therapy Monitoring of hematologic parameters with particular
emphasis on leukocyte and
differential counts and of renal function, including urinary protein excretion, is most
important. Liver enzymes as well as
electrolytes also should be monitored.
SYSTEMIC GLUCOCORTICOIDS Systemic use of glucocorticoids should be restricted
to a few selected patients with
refractory psoriasis. Although transient improvement can be achieved, this is almost
always accompanied by a severe
rebound to an even worse situation than before therapy. Transition from psoriasis
vulgaris into generalized pustular
forms after withdrawal of systemic glucocorticoids can be seen.
EXPERIMENTAL APPROACHES Based on the evidence that psoriasis is a T cell
mediated inflammatory disease, a
number of new therapeutic approaches have been developed. 82
Strategies targeting cellular epitopes on T cells or antigen-presenting cells Targeting
activated T cells, which are
thought to be of primary importance for the pathogenesis of psoriasis, is a principle
adressed in a number of new
therapeutic approaches. A fusion protein of IL-2 and diphtheria toxin (DAB 389IL-2) was
given intravenously to patients
with severe psoriasis and led to improvement of only a subgroup of patients. 83 IL-2
signaling pathways also can be
abrogated by blockade of IL-2 receptors (CD25, a-chain). Treatment with the specific
monoclonal antibody basiliximab

was found to be effective in a patient with active psoriasis. 84 However, in an open

study in plaque-type psoriasis, the
anti-CD25 antibody daclizumab showed only a 30 percent reduction of severity score
after 8 weeks of therapy. 85
Treatment with the fusion protein blocking LFA3-CD2 interaction (alefacept, Amevive)
led to improvement of up to 53
percent in the PASI score in a recent study. 86 There is evidence that alefacept
treatment preferentially reduces the
number of memory T cells (CD45RO+).
Strategies targeting cytokines By using a monoclonal antibody against TNF-a
(infliximab, Remicade) or a fusion
protein mimicking the TNF-a receptor (etanercept, Enbrel), improvement of lesions can
be achieved in plaque-type
psoriasis. 87 , 88
Strategies using recombinant cytokines Systemic application of human recombinant IL10 proved to be efficacious at
least in a subgroup of patients. 89 This therapy lead to to a variety of changes in T cell
function and cytokine secretion in
vivo, as demonstrated recently. 90
OTHER NEW DRUG DEVELOPMENTS
Macrolactams Macrolactams show improvement of lesions by topical use under
occlusion, not, however, when applied
without oclusion. 91 , 92 A recent report show a high efficacy in psoriasis within a short
time when the macrolactam
pimecrolimus (SDZ ASM 981; Elidel) was given orally.
Other New Methods to Treat Psoriasis
Among a variety of newly described methods for treatment of psoriasis, use of the
excimer laser may be of future
importance. This laser generates light at 308 nm in the UVB range. In a first study it was
shown that about four
treatments lead to improvement of lesions with a sustained treatment response. 93
COMBINATION THERAPY A combination of different therapeutic principles may help to
speed resolution of the lesions,
reduce adverse events, and reduce overall doses when systemic compounds are used.
Several combination regimes
have already been established for clinical use, such as topical glucocorticoids with UVB
or PUVA, retinoids with PUVA
(Re-PUVA), and vitamin D 3 and analogues or tazarotene with UVB. The combination of
coal tar baths, UVB, and
anthralin is known as the Ingram method. Goeckerman in 1925 introduced the widely
used combination of coal tar
application followed by suberythemic doses of UV light. Classic anthralin treatment
followed by UVB or bath PUVA is also
a very effective combination regimen. More recent studies indicate that combining
cyclosporine with calcipotriol or

anthralin augments efficacy and reduces cyclosporine dose. Calcipotriol also improves
the response to PUVA.
ROTATION TREATMENT To minimize risk to the patient with severe psoriasis requiring
systemic treatment, rotation
therapy should be performed. Changing between different compoundswith respect to
individual risk factors, cumulative
dose (for MTX), response, and duration of therapyshould be performed at intervals.
Recently published guidelines for
rotation therapy may be helpful in scheduling long-term systemic treatment.