Anthralin (dithranol in the United Kingdom) is a hydroxyanthrone derivative that
inhibits DNA synthesis, mitotic activity, and a variety of enzymes crucial to reducing
It is effective for treatment of widespread, discrete psoriatic
plaques, but its use has declined in recent years with the availability of more
cosmetically appealing preparations. Traditionally, it was applied as a stiff paste
overnight and used in conjunction with coal tar baths and UVB light (i.e., Ingram
regimen). Most cases of chronic plaque psoriasis clear in 3 weeks. The primary
disadvantages of anthralin are its irritant nature and property of staining skin and
clothing. Anthralin also can precipitate generalized psoriasis if applied to unstable
psoriasis (i.e., plaque transformation to pustular form).
When used, the most current anthralin regimen is a once-daily application of a 1%
that limits its use is the brown-to-purple staining of the skin, hair, clothing, furniture,
and bedding that occurs immediately with use. Plastic gloves should be used, as well
as old bed linens and clothing for sleep. If possible, contact with the face, eyes,
mucous membranes, and nonpsoriatic skin should be avoided because of irritant
properties. Irritation is a problem and should be evaluated every 48 hours. Patients
can apply petroleum jelly around lesions to avoid anthralin contact with unaffected
skin. Anthralin is used daily for clearing of psoriasis, then once or twice weekly for
maintenance therapy, after a response is seen at 2 to 3 weeks. Short-course regimens
clear 32% of lesions and produce greater than 75% improvement in half of patients
after 5 weeks. These regimens are comparable in effectiveness to the Ingram regimen
and topical corticosteroids, and are associated with fewer adverse drug events.
Calcipotriene (calcipotriol in Europe) is a topical vitamin D3 analog that suppresses
keratinocyte proliferation and has anti-inflammatory effects.
twice daily as a cream, ointment, foam, or solution. Although systemic absorption is
slight and the vitamin D effects of calcipotriene on calcium and bone metabolism are
about 100 to 200 times less than those of 1,25-dihydroxyvitamin D3
levels and urinary calcium excretion should be monitored to prevent serious adverse
effects. A 100-g/week limit should be enforced; exceeding this limit results in
negative effects on calcium and bone metabolism. Other adverse effects of
calcipotriene, such as lesional and perilesional irritation, burning, stinging, pruritus,
erythema, and scaling, occur in about 30% of patients and preclude use on the face or
in intertriginous areas. When used concurrently with topical salicylic acid,
calcipotriene will be chemically inactivated.
Calcipotriene may be the topical maintenance treatment of choice in patients with
generalized mild-to-moderate psoriasis. The drug is usually effective, relatively easy
to apply, odorless, and nonstaining (cream, ointment, or scalp solution). Most
patients see improvement, although not clearing, of psoriatic plaques at 2 weeks
when treated with calcipotriene, often in combination
with potent topical corticosteroids.
42 A maximal response is usually seen at 6 to 8
weeks. Of treated patients, 57% experience greater than 75% clearance of psoriatic
plaques, which is comparable to that achieved with corticosteroids, albeit slower in
onset and associated with more skin irritation.
30,39 Tachyphylaxis has not been a
Calcitriol is an active form of vitamin D3
that blocks keratinocyte proliferation. The
ointment should be applied twice a day, while avoiding the face, eyes, and lips. Use
should not exceed 200 g/week. Hypercalcemia has occurred in about 25% of
patients, and calcitriol should be held until calcium levels return to normal.
Nephrolithiasis, hypercalciuria, and irritation of the skin have been reported with
calcitriol use. Skin irritation, however, is less than with the use of calcipotriene.
Caution should be exercised when combining calcitriol with phototherapy because it
is inactivated by ultraviolet light and its vehicle blocks ultraviolet light.
patients should apply calcitriol after phototherapy. Calcitriol effects are seen as early
as 2 weeks, peak in about 8 weeks, and equal calcipotriene efficacy. Approximately
65% of patients continued to show improvement at 52 weeks of therapy.
Tazarotene is a topical synthetic retinoid that is rapidly converted to its biologically
active metabolite, tazarotenic acid.
31,45 By interacting with the predominant retinoid
receptors on the skin surface regulating gene transcription, retinoic acids normalize
abnormal keratinocyte differentiation, reduce hyperproliferation, and decrease
inflammation associated with psoriasis.
45 Treatment success rates compare favorably
with corticosteroids (52% clearing of all lesions; 70% clearing of trunk and limb
lesions). The antipsoriatic effects of tazarotene are sustained for a longer period after
treatment compared with corticosteroids.
34,46 Because local skin irritation and
pruritus are common adverse effects of tazarotene use, combination therapy with
corticosteroids not only provides additive antipsoriatic effects, but also reduces
47 Because oral retinoids are known teratogens, tazarotene
is a category X drug and is contraindicated during pregnancy. Women should be
warned of the potential risk and the need to use adequate contraception while using
Similar to calcipotriene, tazarotene works slowly. It is available as a gel, which
many patients find more cosmetically appealing than an ointment. It is also effective
in a once-daily regimen, which might help to improve compliance.
Phototherapy with ultraviolet (UV) light has a long history of use in the treatment of
psoriasis. Unlike immunosuppressive agents, phototherapy is thought to target
effector immune cells and upregulate regulatory T cells. Phototherapy also reverses
epidermal barrier abnormalities, thus restoring cutaneous homeostasis.
locally, UV light can be used as an outpatient modality, and newer options for home
treatments have become commonplace.
cost when compared with biologic agents.
50 Different protocols require daily
exposure or multiple times per week for varied lengths of time, depending on patient
variables. The optimal effect of UVB on psoriasis is a dose that produces minimal
erythema at 24 hours. The usual time to induce clearing of psoriasis is approximately
Ultraviolet B light, sunburn spectrum 290 to 320 nm, induces pyrimidine dimers,
inhibits DNA synthesis, and depletes intraepidermal T cells found in psoriatic
epidermis (i.e., UVB has antiproliferative and local immunologic effects).
light, unlike ultraviolet A (UVA) light, is effective without additional sensitizers
(i.e., psoralens). UVB therapy is generally considered pleasant to use and relatively
nontoxic. Typically, 60% of patients with chronic plaque psoriasis experience
clearing, and an additional 34% achieve a 75% clearance with UVB treatment for 7
35 Humidity and heat from sunlight provide additional positive effects.
Narrowband UVB (NB-UVB) phototherapy, having sunburn spectrum of 311 nm, has
been found to be more effective than broadband UVB (BB-UVB)
not demonstrated superiority to psoralens plus ultraviolet A (PUVA) light therapy in
terms of clearing psoriatic lesions.
In a literature review comparing PUVA with
NB-UVB, PUVA tends to clear psoriatic lesions more reliably, with fewer sessions,
and with longer-lasting clearance; however, this must be balanced with the increased
risk of PUVA in causing skin cancers.
In another literature review, NB-UVB was
found to be more effective than BB-UVB and was also safer than PUVA.
The greater efficacy of PUVA, however, may be offset by the short-term adverse
effects of psoralens (e.g., nausea, headaches), the greater incidence of phototoxic
reactions (erythema), and the inconvenience of wearing photoprotective eyewear
after treatments. At present, NB-UVB may be preferred because the available data
suggest no or minimal risk of carcinogenesis compared with PUVA, it is safer to use
in children and pregnant patients, it is devoid of drug-related (psoralen) adverse drug
events, and there is no requirement for the use of posttreatment photoprotective
eyewear. Although not definitively proven, it is hypothesized that NB-UVB will
produce less long-term photodamage and fewer skin cancers than PUVA.
Ultraviolet B treatments are administered 3 times weekly. The use of pretreatment
emollients (e.g., petrolatum, mineral or “baby” oil, Eucerin) applied before UVB
exposure, long thought to improve results by aiding in descaling or by enhancing
UVB penetration, actually inhibits its penetration and should not be used.
skin clears, therapy is discontinued gradually over the course of 2 to 4 months to
prolong remission. The risks of UVB radiation and sunlight are similar: sunburn,
Regimens combining UVB with anthralin (Ingram regimen) or tar (Goeckerman
regimen) have been used for years, theoretically taking advantage of the
photosensitizing properties of tar and anthralin. The Goeckerman regimen, which
consists of use of UVB light and 1% to 10% crude coal tar, involves daily
application of coal tar for at least 4 hours, along with UVB exposure. Crude coal tar
has been shown to be superior to cleaner tar preparations and other tar derivatives,
using a 2-hour application before broadband UVB exposure. A petrolatum base, with
a greasy sensation, was not superior to hydrophilic ointment, which has better
cosmetic appeal and is easier to apply.
The Ingram regimen combines daily application of anthralin plus coal tar baths
with exposure to UVB light, with combination results superior to UVB monotherapy.
These two regimens are reported to clear plaques in 75% of patients treated for 6
weeks for chronic plaque psoriasis (vs. 56% with UVB alone). The total number of
treatments and the total UVB dose required for clearing are less in the combination
57 Methods of classical treatments are not standardized, and different
protocols in different treatment settings are used. Combinations of anthralin with
superpotent corticosteroids or with coal tar may be preferred if systemic therapies
are not effective or contraindicated.
58 Both the Goeckerman and Ingram regimens can
decrease the severity of widespread psoriasis in 3 to 4 weeks, induce remissions that
last for weeks to months, and may reduce the long-term adverse effects of UVB
57 A newer interest is the use of the Goeckerman regimen in those patients
who are refractory to biologic agents.
In summary, the first step in the treatment of M.M. would be a high-potency
corticosteroid ointment twice daily, along with a coal tar ointment at night. If this is
ineffective, either calcipotriene ointment can be added twice daily or tazarotene gel
can be used once a day for 8 weeks. Once control is achieved, M.M. may use
calcipotriene or tazarotene without topical corticosteroids; these products do not
cause corticosteroid atrophy and do not have the potential for systemic adverse
effects associated with topical corticosteroids. Topical anthralin, with or without
UVB, can be used for resistant cases.
diffuse, erythematous plaque-like lesions now extending over 80% of his body. The areas have become
expresses frustration with the messiness of the current topical regimen. He has reinstituted topical
consultant. Which “systemic” therapy would be most appropriate for G.L.’s psoriasis at this point?
Systemic therapies for psoriasis include PUVA, acitretin (the systemic retinoid),
methotrexate; cyclosporine; and apremilast. Biologic agents, including the tumor
necrosis factor (TNF)-α inhibitors (infliximab, etanercept, adalimumab, golimumab,
ustekinumab, and secukinumab), have also been used for psoriatic lesions.
Although PUVA and methotrexate are commonly used, cyclosporine and the
immunomodulatory agents are being used increasingly more as experience is gained
with them for treatment of severe psoriasis.
25,61 The choice of agents depends on
patient and drug characteristics. Because patients with psoriasis generally have the
disease for the rest of their lives, the goal of treatment is not just safe and effective
weaning or discontinuation of UVB, PUVA, and methotrexate. From a histologic
perspective, these drugs have been shown to induce remittive cellular changes. In
contrast, partial-to-full doses of acitretin or cyclosporine are necessary to maintain
therapeutic effects, because they induce suppressive rather than remittive
histopathologic changes. For example, relapse will occur in most patients in a
predictable manner 2 to 4 months after cyclosporine is discontinued.
biologic therapy has demonstrated a very satisfactory antipsoriatic effect; however,
the loss of the therapeutic response over time has been reported. Of interest, the
addition of NB-UVB to the use of immunomodulatory agents that have lost this
response in the control of moderate-to-severe cases in adults has been demonstrated
to recover the initial response.
Photochemotherapy combines psoralens with UVA light in the 320- to 400-nm
spectrum. The psoralens (methoxsalen, 8-methoxypsoralen, and trioxsalen) are a
group of photoactive compounds that, on absorption of UV light, are both
antiproliferative and immunomodulatory. When photoactivated by UVA, psoralens
form monofunctional adducts and cross-links with pyrimidine bases. PUVA also
inhibits cytokine release and depletes both epidermal and dermal T cells. As
measured by extent of T-cell depletion and decreases in delayed hypersensitivity,
PUVA has greater immunomodulatory effects in the skin than UVB. Use of PUVA for
scalp or nail involvement is limited, however, because of lower exposure.
Remissions are longer in duration than with UVB. Psoralens are not active without
Photochemotherapy is used to control severe, recalcitrant, disabling plaque
psoriasis. After 10 to 20 treatments over the course of 4 to 8 weeks, more than 80%
of patients experience clearing of symptoms, which can be maintained with periodic
64 UVA penetrates the skin more deeply than UVB and
may have marked effects on the dermis. The use of PUVA requires careful
consideration and adherence to strict photoprotective measures. Patients unwilling to
adhere to PUVA-related precautions may prefer UVB treatment because it is much
The peak range for UVA light’s therapeutic action is between 320 and 335 nm. The
most widely used agent, 8-methoxypsoralen, at an oral dosage of 0.6 to 0.8 mg/kg of
body weight rounded to the nearest 10 mg, is taken approximately 1.5 hours before
52 The initial dose is selected on the basis of the patient’s skin
type (i.e., ease of sunburn and inherent skin color). Other options for combination
therapy with UVA include calcipotriol-PUVA (D-PUVA) and retinoid-PUVA
(RePUVA). Both of these modalities have been shown to have greater efficacy as
Acute adverse phototoxic effects, such as partial-thickness burns, erythema, and
blistering, are dose-related and, therefore, are a serious yet preventable complication
65 Other acute adverse drug effects include nausea,
lethargy, headaches, pruritus, and hyperpigmentation. Topical corticosteroid therapy
should be continued until the psoriasis is brought under control. If topical
corticosteroids are discontinued at the start of PUVA, an exacerbation of psoriasis
usually occurs. Patients should wear protective clothing (with long sleeves and high
necklines), use sunscreens that filter out both UVA and UVB, and wear sunglasses
that block UVA after PUVA (see Chapter 42, Photosensitivity, Photoaging, and
Burns). Because methoxsalen has a short half-life and 80% is eliminated within 6 to
8 hours, physical barriers are most important during the 8 hours immediately after
Of greater concern are the potential long-term adverse effects: mutagenicity,
carcinogenicity, and cataract formation. A review of studies demonstrated an
increased risk of nonmelanoma skin cancers following PUVA.
carcinoma has been associated with cumulative PUVA treatments (11-fold increase
in patients who receive more than 260 treatments compared with patients who
received fewer than 160 treatments).
67 Male patients have an increased risk of having
genital squamous cell carcinoma. A relationship exists between the exposure to
PUVA. The risk is first manifested at least 15 years after initial exposure to
67–69 A cohort study evaluated over 13,000 patients for cancer risk by
treatment modality. Patients treated with coal tar did not have increased risk of
malignancies, both dermatologic and nondermatologic, and it is considered a safe
70 Long-term maintenance and high cumulative dosages should be
avoided. Shielding the face and genitalia during treatment and performing annual
examinations to detect skin cancer at an early stage may lessen the risk of long-term
adverse effects of photochemotherapy.
Topical psoralens are extremely photosensitizing and hence difficult to administer.
Application of methoxsalen 0.1% followed
by small UVA doses (i.e., ≤20% of the level of usual doses for oral PUVA) has
been used, however, to treat localized areas and to prevent adverse gastrointestinal
Second-generation systemic retinoids are effective for treatment of recalcitrant
psoriatic disease. Antipsoriatic effects stem from the drug’s ability to modulate
epidermal differentiation and immunologic function in addition to an antiinflammatory action.
71 This latter effect may alleviate the arthritis that accompanies
25,64 Acitretin, a systemic second-line therapy for severe psoriasis, is the
principal metabolite of etretinate. It is 50 times less lipophilic than etretinate and has
a considerably shorter elimination half-life; however, patients taking any retinoid
product should still be monitored closely. It is indicated for patients who have
received extensive radiation with PUVA, as a pretreatment for PUVA (1–3 weeks) to
accelerate the response rate, for patients who fail to respond to UVB with anthralin
or tar, or for patients who are not candidates for methotrexate.
maintenance or intermittent therapy to prevent relapses.
should be assessed at 4-week intervals with dose titrations to reach therapeutic effect
Numerous other adverse effects are associated with acitretin use, including
hypervitaminosis A syndrome (i.e., dry skin, skin thinning and fragility, chapped lips,
dry nasal mucosa, skin peeling, alopecia, and nail dystrophy), retinoid rash,
extraspinal tendon and ligament calcification and bone changes in children,
hyperlipidemia with elevated levels of serum triglycerides and cholesterol, and liver
enzyme alteration and hepatitis.
75 Many patients find the adverse effects of the
retinoids intolerable and discontinue treatment. Topical corticosteroids can reduce
some of the cutaneous retinoid adverse effects.
Acitretin is teratogenic and accumulates in fatty tissues, where it is slowly
released into the bloodstream for up to 1 year after final administration.
strict contraception during treatment and for 2 to 3 years afterward is recommended
69,76 Patients also need to be advised not to donate
blood while taking acitretin and up to 1 year after the end of treatment.
Methotrexate, a folic acid analog, inhibits dihydrofolate reductase needed for
synthesis of several amino acids, pyrimidines, purines, and, subsequently, DNA,
RNA, and protein synthesis. Methotrexate therapy greatly suppresses rapidly
proliferating cells, such as those in psoriatic skin. Antipsoriatic mechanisms of
methotrexate action include inhibition of keratinocyte differentiation and
immunomodulation by destruction of lymphoid cells.
Unlike other cytotoxic drugs, methotrexate produces antipsoriatic effects at
dosages that are much lower than those used in cancer chemotherapy. Methotrexate is
relatively safe and well tolerated, yet the long-term concerns for myelosuppression
and hepatotoxicity (fibrosis and cirrhosis) and the need for periodic liver biopsies
can discourage many patients and physicians from using it.
methotrexate are a particularly potent hepatotoxic combination. Patients with
psoriasis receiving methotrexate have a 2.5- to 5-fold higher incidence of advanced
liver changes than patients with rheumatoid arthritis receiving comparable
80 Methotrexate hepatotoxicity may be related to both cumulative doses and
constant blood levels. Daily administration has been replaced by weekly dosage
schedules for this reason. Liver chemistry tests (i.e., serum alanine aminotransferase,
serum aspartate aminotransferase, serum albumin, and bilirubin) can be within
normal limits, even in the presence of methotrexate-induced liver disease.
Therefore, consensus guidelines call for risk stratification for liver biopsies in all
patients with psoriasis at baseline, and at intervals of approximately 1 to 1.5 g of
cumulative methotrexate dose. Liver function tests, bilirubin, and albumin should be
monitored monthly for the first 6 months, and then every 1 to 2 months thereafter.
Bone marrow depression, nausea, diarrhea, and stomatitis are other adverse
effects associated with methotrexate. Pneumonitis can occur early in the course of
treatment, particularly when methotrexate is given at higher dosages similar to those
used in cancer chemotherapy regimens. Folic acid, 1 mg daily, may prevent some of
these adverse events, but not hepatitis or pulmonary toxicities. Teratogenesis and
miscarriages have occurred, and methotrexate may cause reversible oligospermia. A
number of clinically significant drug interactions may enhance the toxicity of
methotrexate. Drug interactions are most likely to be clinically relevant problems in
patients with decreased renal function.
Relative contraindications to treatment with methotrexate include decreased renal
function, significant abnormalities in liver function (i.e., fibrosis, cirrhosis,
hepatitis), pregnancy or breastfeeding, anemia, leukopenia, thrombocytopenia, active
peptic ulcer disease or infectious disease (tuberculosis, pyelonephritis), alcohol
abuse, and patient unreliability.
77 Conception must be avoided during methotrexate
therapy and for at least 3 months after cessation of methotrexate in men or one full
77 Monthly monitoring of complete blood count with
differential and a platelet count should be performed 7 to 14 days after starting
therapy, and every 2 to 4 weeks for the first few months, then every 1 to 3 months.
Renal function tests (i.e., serum creatinine, BUN) should be obtained at 2- to 3-month
The positive dermatologic effects of cyclosporine highlight the importance of immune
alterations in the pathogenesis of psoriasis. The toxicity and the short duration of
remissions induced by cyclosporine and tacrolimus limit their usefulness.
Cyclosporine is generally reserved for patients with extensive psoriasis who have
not responded adequately to topical agents, UVB, PUVA, and other systemic agents.
In psoriasis, cyclosporine primarily acts by inhibition of calcineurin, which is
necessary for interleukin-2 (IL-2) production. Interleukin-2 amplifies helper T cells
and cytotoxic lymphocytes. Decreased IL-2 production leads to a decline in activated
CD4 and CD8 cells in the epidermis. Cyclosporine also inhibits TNF-α and
, both of which are involved in the chemotaxis of inflammatory cells; it
inhibits release of cytokines and the growth of keratinocytes.
Cyclosporine is used at relatively low dosages for the treatment of psoriasis. In
general, 2.5 to 6 mg/kg of cyclosporine, in one or two divided doses, is
recommended for the initiation of psoriasis treatment. Rapid improvement of plaque
psoriasis is expected, with 30% of patients experiencing clearing of psoriatic
plaques and 50% achieving greater than 75% clearing of lesions within 10 weeks at
a dose of 2 to 3 mg/kg/day. Many people relapse 2 to 4 months after the
discontinuation of cyclosporine therapy.
82 Cyclosporine showed comparable efficacy
to methotrexate in patients with psoriasis with average doses of 4.5 mg/kg/day and
Drug-induced renal impairment is common with cyclosporine use, but usually
reversible. Hypertension, secondary to vasoconstrictive effects on the smooth muscle
of renal blood vessels or drug-induced arteriolar hyalinosis, is dose dependent and
in onset. Blood pressure and serum creatinine should be monitored closely in
patients receiving cyclosporine.
79 Hypokalemia, hypomagnesemia, hyperuricemia,
gingival hyperplasia, hypercholesterolemia, hypertriglyceridemia, adverse
gastrointestinal effects, hypertrichosis, fatigue, myalgia, and arthralgia also have
been attributed to cyclosporine therapy.
80 The risk of skin cancer, lymphomas, and
solid tumors can also increase.
81,82 Patients should be cautioned about excessive sun
exposure and should not receive concurrent UVB or PUVA treatment during
cyclosporine therapy because of an increased risk of nonmelanoma skin cancers.
PUVA is effective in 80% to 90% of patients, and G.L.’s severe, extensive, plaque
psoriasis should be expected to respond accordingly. The systemic drugs (e.g.,
methotrexate, cyclosporine) may be preferred if G.L. had systemic symptoms (e.g.,
psoriatic arthritis). Although 3 times weekly PUVA treatments can be disruptive to
work schedules, G.L. is self-employed and presumably has some flexibility in his
working hours, and this would be a good option for him.
Phosphodiesterase 4 (PDE4) Inhibitors
cAMP in T cells. This results in decreased expression of cytokines and other
proinflammatory mediators, but increased expression of anti-inflammatory
84 Mesenchymal cells, which express PDE4, are found in keratinocytes
within the dermis, smooth muscle, and vascular endothelium.
demonstrated that patients randomized to apremilast 20 mg twice daily achieved 24%
and 29% PASI-75 at weeks 12 and 16, compared to 10.3% and 6% of those in
86,87 Of note, all patients enrolled had previously failed other therapy
or were receiving concurrent therapy for psoriasis. Therefore, apremilast should not
be considered a first-line agent in the treatment of plaque psoriasis.
The recommended dose for apremilast is a 5-day titration up to 30 mg twice daily.
The most common adverse effects with apremilast include gastrointestinal (i.e.,
diarrhea and nausea) and headache. Other adverse effects included upper respiratory
infections and rebound psoriasis in 0.3% of patients after discontinuation of therapy.
Apremilast is metabolized via the CYP 3A4 pathway and therefore should be
evaluated for any drug–drug interactions prior to starting therapy. The dose of
apremilast should be reduced when used in patients with impaired renal function
(e.g., creatinine clearance less than 30 mL/minute).
CASE 41-2, QUESTION 2: Does G.L. have options to decrease adverse effects and cost of his PUVA
No form of therapy used in psoriasis today is without toxicity. Rotational therapy
involves the use of alternating monotherapies, which allows the patient to experience
extended intervals of a particular treatment.
88 When used in long-term maintenance,
rotational therapy limits adverse effects associated with either long-term use of one
specific agent or the additive or synergistic interactions when multiple therapies are
used concurrently. As discussed, the relative risk of skin cancer associated with
PUVA increases after 160 treatments. If a patient in remission is rotated off PUVA to
another treatment after 100 exposures, the skin has time to recuperate from the light
therapy, and PUVA can eventually be reinstated presumably with lesser risk.
Rotational therapy assumes that the patient can tolerate three to four alternative
treatments with unrelated toxicity profiles.
88 By rotating each treatment after 12 to 18
months of cumulative use, the potential for long-term toxicity associated with any
single treatment is minimized. With this theoretic rationale, cyclosporine could be
used for a limit of possibly 3 to 6 months, thus inducing a remission. The patient
could then be rotated to another treatment (e.g., methotrexate or PUVA) for
Psoralens and UVA irradiation become noticeably effective in 80% to 90% of
25 The regimen is time consuming because UV radiation
treatments must be administered at least 3 times a week. Methoxypsoralen (8-MOP)
is administered (0.6–0.8 mg/kg of body weight), followed by UVA (dose selected
based on skin type, ease of sunburn, and inherent skin color) about 75 to 90 minutes
later when psoralen blood levels peak. PUVA-induced erythema generally appears
later than with UVB therapy, reaching a peak by 48 hours. Consequently, treatment
should not be administered more frequently than every second day. The time to
produce clearing of psoriatic plaques with PUVA takes longer than with UVB
therapy (average 10 weeks compared with ≤3 weeks for UVB).
must be decreased slowly once plaques have been cleared (frequency of treatment is
reduced during 2–3 months) to prevent recurrence of psoriatic plaques. In contrast,
UVB therapy can be ceased abruptly.
Taking time off from work 3 times weekly for photochemotherapy can be
disruptive to some patients’ work or school schedules. Technologic advances in
home phototherapy equipment have provided patients with choices for therapy in
settings that are familiar and comfortable, in addition to continued improvements in
41 Advantages of home phototherapy include improved quality of
life, greater convenience, lower cost, and less time lost from work and social
Psoralens and UVA should be avoided in patients with a history of skin cancer, in
children, during pregnancy, in patients who are immunosuppressed, and in those who
have light-colored skin that burns rather than tans. Absolute contraindications to
treatment with PUVA include a history of photosensitivity diseases (i.e., lupus
erythematosus, porphyria), idiosyncratic or allergic reactions to psoralens, arsenic
intake, and exposure to ionizing radiation, skin cancer (relative contraindication),
pregnancy, and lactation. Techniques to minimize cumulative dosage of radiation and
reduce the risk of long-term adverse effects of photochemotherapy include use of
sunscreen, protective clothing, and sunglasses, and use of combination therapy
(RePUVA). Other photosensitizing drugs (e.g., fluoroquinolones, phenothiazines,
sulfonamides, sulfonylureas, tetracyclines, and thiazides) should be avoided in
Rotational therapy could be considered at a later time, depending on G.L.’s
response and tolerance of PUVA.
therapy would be most appropriate to treat both R.T.’s skin and joint complaints?
Psoriatic arthritis (PsA) is a distinct form of inflammatory arthritis that is usually
seronegative for rheumatoid factor. In various reports, 6% to 39% of patients with
psoriasis experience PsA, and the prevalence is increased among patients with
18 Nail involvement occurs in greater than 80% of patients
with PsA, as compared with 30% of patients with only cutaneous psoriasis.
clinical subsets of PsA have been identified: distal interphalangeal arthritis (classic;
5%–10%, often accompanied by nail changes), arthritis mutilans (5%, starts in early
age, accompanied by osteolysis with severe deformities of fingers and toes),
symmetric polyarthritis (rheumatoid-like; <25% incidence, milder course),
asymmetric oligoarthritis (most prevalent; 70%, proximal and distal interphalangeal
joints, metacarpophalangeal joints, knee, and hip), and spondylitis (5%–40%, often
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