PHOTOTHERAPIES & PHOTOCHEMOTHERAPIES

• consists of using nonionizing electromagnetic radiation, either UVA or UVB, as light therapy
to treat
psoriatic lesions

NB-
UVB

(Ingram regimen)

• UVA → generally given with a photosensitizer, such as an oral psoralens, to

enhance efficacy—thisregimen is known as PUVA (Psoralen and UVA Light)

Comparative Efficacy:

PUVA > NB-UVB > BB-UVB

• due to greater availability of UVB treatment centers,
• more evidence of the efficacy of UVB treatments for psoriasis phototherapy for psoriasis
currently uses UVB or NB-UVB where available.
(in particular, NB-UVB) Failure of NB-UVB may
justify PUVAtherapy
• increasing concerns about PUVA toxicities (including skin cancers)
Failure of NB-UVB may justify PUVAtherapy
 MOA: UVB interferes with protein and nucleic acid
synthesis, leading todecreased proliferation of epidermal
keratinocytes

UVA has similar effects on epidermal keratinocytes. However,

because of deeper penetration into the dermis, it also has
effects on dermal dendritic cells, fibroblasts, endothelial cells,
mast cells, and skin-infiltrating inflammatorycells including
granulocytes and T lymphocytes

A/E:

, especially with
higher dosages.

* should be used with caution for patients with

photosensitivity concerns,and drug interactions include
photosensitizing medications such as tetracyclines
* Patients must be provided with eye protection during
UVB, NB-UVB, or PUVA treatments, and for 24 hours or
the remainder of the day after PUVAtreatments.

patients receiving PUVA therapy may experience GI symptoms such as

nausea or vomiting
* minimized by taking the oral psoralens with food or milk.

*For patients also receiving oral retinoids (RE-PUVA), the UVA dose should be
reduced by one third
 • Long Term PUVA use:

- Photoaging
- development of PUVA lentigines
- potential for increased cataract formation (Psoralens bind to proteins in the lens of the
eye)
- 14-fold increase in the incidence of squamous cell carcinoma (SCC)
- increase the risk of basal cell carcinoma and possibly melanoma (may occur 15 years
after the first treatment)
 SYSTEMIC THERAPIES

• Systemic therapies are the mainstay of treatment for patients with

moderate tosevere psoriasis, with topical therapies remaining as
useful adjuncts.

• Systemic therapies include the following traditional agents acitretin

cyclosporinemethotrexate
mycophenolate mofetil (MMF) hydroxyurea as well as the newer BRMs,
specifically adalimumab, alefacept, etanercept, infliximab,
and ustekinumab.
 ACITRETIN :

• second-generation, systemic retinoid that has been approved for the treatment of psoriasis since 1997
• more commonly used in combination with topical calcipotriol or phototherapy

Dose and Efficacy:

optimal initial dose - 25 mg/day
maintenance dose- 25–50 mg/day

efficacy appears to be dose dependent

low-dose acitretin (25 mg/day) is safer and better tolerated than higher-dose (50 mg/day) therapy

A/E:
Common- hypertriglyceridemia : - mucocutaneous adverse effects- dryness of the eyes, nasal and
oral mucosa, chapped lips, cheilitis,
epistaxis, xerosis, brittle
nails, and burning or sticky skin
Less
Common- retinoid dermatitis

Long term use: Periungual pyogenic granulomas

Rare: skeletal abnormalities—such as disseminated idiopathic skeletal hyperostosis (DISH)

syndrome

Indications: generalized pustular and erythrodermic psoriasis (most responsive to etretinate or

acitretin as
monotherapy )

Remarks:
- should not be used for women of childbearing age unless they are able and willing to use effective
birth control not only for the duration of acitretin therapy but also for 3 years after discontinuing the
agent.
- Men receiving acitretin should not donate blood for a similar time period.

- Ethanol should be avoided during therapy and for 2 months after drug discontinuation
Reason: since it causes the transesterification of acitretin to etretinate, which has a much longer
elimination half-life
Periungual pyogenic granulomas
 CYCLOSPORINE

- systemic calcineurin inhibitor

INDICATION:
- efficacious for both inducing remission and maintenance therapy for patients with moderate to severe
plaque
psoriasis.
- It is also effective in treating pustular, erythrodermic, and nail psoriasis

DOSING:
High-dose approach: 5 mg/kg daily, then tapered.
Low-dose approach: 2.5 mg/kg daily, increased every 2–4 weeks up to 5 mg/kg daily.
Tapering is recommended on discontinuation.

For patients discontinuing cyclosporine, a gradual taper of 1 mg/kg/day each week may prolong the time
before
relapse, as compared with abrupt discontinuation

Abrupt discontinuation resulted in a dramatic rebound of psoriasis in a few cases. Because more
than half of patients discontinuing cyclosporine will relapse within 4 months, patients should be provided
withappropriate alternative treatments shortly before or after discontinuing cyclosporine therapy

EFFICACY: more effective than etretinate and similar or slightly better in efficacy than methotrexate
A/E:
• cumulative renal toxicity, hypertension, and hypertriglyceridemia
- risk of SCC and other nonmelanoma skin cancers increases with duration of treatment

Monitoring Parameters:
Baseline blood pressure, serum creatinine, serum urea nitrogen, triglycerides, complete blood count, uric
acid, potassium and magnesium should be obtained before initiating therapy, every 2 weeks for the
first 12 weeksof therapy, and monitored monthly thereafter during therapy.
Age-appropriate malignancy screens
*patients should be seen for dental examinations at least yearly because of the risk of gingival hyperplasia
Recommendations:
The 2009 Canadian Guidelines recommended that cyclosporine be normally reserved for
intermittent use in periods up to 12 weeks for most patients with psoriasis other recommendations are
for periods of 1 year or up to 2 years.Risk of toxicity increases with treatment duration

DRUG INTERACTIONS:
As a CYP3A4 substrate, cyclosporine has significant drug interactions
Grapefruit juice will also increase cyclosporine concentrations.

Drugs that can increase cyclosporine

Concentrations

• calcium channel blockers (verapamil, diltiazem, and nicardipine)amiodarone

• thiazide diuretics

Drugs that can reduce cyclosporine

Concentrations
• anti-convulsants (carbamazepine, oxcarbazepine,
• phenobarbital, phenytoin, valproic acid)
• efavirenz
• St. John’s work
• macrolide antibiotics
• allopurinol
• oral contraceptives
• ezetimibe
• selective serotonin reuptake inhibitors (fluoxetine, sertraline
• fluoroquinolones (ciprofloxacin, norfloxacin)
• antifungals (ketoconazole,
itraconazole, fluconazole,
voriconazole)
 METHOTREXATE

Effects: direct antiinflammatory benefits due to its effects on T-cell gene expression and also has
cytostaticeffects

Dosing and Efficacy:

Start with a test dose of 2.5 mg and then gradually increase dose until a therapeutic level is achieved
(average range, 10–15 mg weekly; maximum, 25–30 mg weekly)

- more efficacious than acitretin and similar or slightly less efficacious than cyclosporine

A/E:
most signifcant- cumulative liver toxicity
Other adverse effects include significant nausea, pulmonary toxicity, pancytopenia, acute
myelosuppression,
megaloblastic anemia, and a small but significant increase increase in lymphoma

Monitoring Parameters:
Baseline CBC and LFTs.
Monitor CBC and LFTs weekly until target dose is achieved, then every 4–8 weeks.
Liver biopsy every 1.5 g (high risk) to every 3.5–4.0 g (low risk) of cumulative dose or use
procollagen III assay

• Consistent with a DHFR-independent mechanism of action, concomitant administration of

folic acid (1–5mg/day) reduces certain side effects, such as nausea and megaloblastic anemia,
without diminishing theefficacy of antipsoriatic treatment (except on MTX days)

Risk factors for hepatotoxicity from methotrexate include the following:

• a history of or current alcohol consumption
• persistent abnormal liver chemistry studies,
• history of liver disease including chronic hepatitis B or C
• family history of inheritable liver disease
• history of significant exposure to hepatotoxic drugs or chemicals
• diabetes mellitus
• obesity
• hyperlipidemia
 TOXICITY:

• Leucovorin calcium (folinic acid) is the only antidote for the hematologic toxicity of MTX.
When an overdose is suspected, an immediate leucovorin dose of 20 mg should be given parenterally
Or Orally, and subsequent doses should be given every 6 hours

DRUG INTERACTIONS:

• serum albumin binding interactions with salicylates, phenytoin, sulfonamides/trimethoprim,

ciprofloxacin, andthiazide diuretics, potentially increasing toxicity.
• Drugs that can reduce methotrexate renal elimination such as acidic drugs, including
salicylates or vitamin C will
• also increase serum methotrexate levels and hence increase toxicity.
• In addition, drugs with hepatotoxic potential may pose an additive risk with methotrexate
use.
 SYSTEMIC THERAPY WITH BIOLOGIC RESPONSE MODIFIERS
• Some BRMs have proven efficacy for psoriasis, however, there are differences among these
agents, including mechanism of action, duration of remission, and adverse effect profile.

• BRMs are sometimes recommended for first-line therapy, alongside conventional

systemic agents, for patients with moderate to severe psoriasis.

• BRMs currently available for treatment of psoriasis include adalimumab, alefacept,

etanercept, infliximab, and ustekinumab.

• Tumor Necrosis Factor-Alpha Inhibitors.

• Dysregulation of TNF-alpha production has been associated with various inflammatory.

conditions, including rheumatoid arthritis, inflammatory bowel disease, ankylosing
spondylitis and psoriasis.

• Elevated TNF-a levels are seen in both the affected skin and serum of patients with
psoriasis: and these elevated levels have a significant correlation with psoriasis severity.

• The biologic agents etanercept, adalimumab, and infliximab are TNF-alpha inhibitors.

• They offer the prospect of more rapid disease control than is commonly seen with the other
BRMs.

• After successful control of psoriasis, TNF alpha levels are reduced to normal.
 Alefacept

• MOA: Amevive is a dimeric fusion protein that binds to CD2 on T cells to inhibit→cutaneous T-cell
activation and proliferation. It also produces a dose dependent decrease in circulating total
lymphocytes.

• Dose:

Dosing is intended to be intermittent.

• Alefacept is given for a 12-week course, recommended dose is 15 mg intramuscularly once weekly for
12 weeks.

• Maximal Response was generally seen by 6 to 8 weeks in responders.

• Adverse effects:

Are mild and include pharyngitis, flu-like symptoms, chills, dizziness, nausea, headache,
injection site pain and inflammation
 Ustekinumab

• *Ustekinumab is an IL-12/23 monoclonal antibody and the newest BRM, having been approved for
the treatment of psoriasis in adults 18 years or older with moderate to severe plaque.

Dose:
• Dosing is 45 mg for patients weighing 100 kg (220 h) or less, and 90 mg for those of higher weights.
• Ustekinumab is administered subcutaneously at weeks 0 and 4, then every 12 works as maintenance
therapy.

Adverse effects:
• Upper respiratory infections, headache, and tiredness, serious -tubercular, fungal, viral infec tions, and
cancers.
• In addition, a reversible posterior leukoencephalopathy syndrome.
 COMBINATION THERAPIES

• Combination therapies may be beneficial in the management of plaque psoriasis generally to either
enhance efficacy or minimize toxicity.
 ALTERNATIVE DRUG TREATMENT

1) Mycophenolate mofetil:
• Mycophenolate mofetil inhibits DNA and RNA synthesis and may have a lymphocyte anti-
proliferative effect.

Dose:
• The usual dose is 500 mg orally four times daily, up to a maximum of 4 g daily.

Adverse effects:
• Increased incidence of opportunistic infections such as cytomegalovirus, cryptococcosis, candidiasis,
and Pneumocystis jirovecii.

• Cases of progressive multifocal leukoencephalopathy have abo been reported.

• There may be an associated risk of malignancy.

2) Hydroxyurea:

• Hydroxyurea inhibits cell synthesis in the S phase of the DNA cycle.

Dose:

• The typical dose is 1 g daily, with a gradual increase to 2 g daily as needed and as tolerated.

Adverse effects:
• Significant bone marrow suppression, lesional erythema, localized tenderness, and reversible
• hyperpigmentation.
 Reference:

DiPiro's Pharmacotherapy: A Pathophysiologic Approach, 12th Edition Joseph T. DiPiro, Gary C. Yee,
Stuart T. Haines, Thomas D. Nolin, Vicki L. Ellingrod, L. Michael Posey

Medscape