Dermatology

Psoriasis

Psoriasis

Are You Confident of the Diagnosis?

Psoriasis is a chronic inflammatory skin disease process involving immune-mediated cutaneous inflammation and keratinocyte proliferation. The diagnosis is based upon a combination of both history and physical examination parameters. Typically, psoriasis is characterized by scaly, erythematous patches, papules, and plaques that are often pruritic and can be painful. The disease is a chronic disease that can wax and wane in severity and is typically improved with treatment. Rarely, spontaneous remissions can occur.

There are multiple subtypes, includingŠpsoriasis vulgaris, plaque type psoriasis, inverse psoriasis,Šerythrodermic psoriasis, guttate psoriasis, nail unit psoriasis, andŠpustular psoriasis, which are determined by the onset of disease and appearance/location of the lesions. Clinical findings of multiple subtypes may overlap in the same patient as well.

Psoriasis subtypes

Plaque psoriasis is the most common form, affecting 80-90% of patients. The characteristic finding for this subtype is sharply demarcated, erythematous plaques with dry, thin, silvery to whiteŠscale over top; the plaquesŠvary in size and are typically round to oval in shape. They are most often located on the scalp, trunk, buttocks, and extremities, preferentially involving extensor surfaces, umbilicus, and supragluteal cleft (Figure 1). Painful fissuring may occur. The extent of body surface involvement varies substantially from limited to extensive disease (>5% body surface area).

Figure 1.

Plaque psoriasis.

Inverse psoriasis is characterized by erythematous plaques with minimal scale located in skin folds, such as the axillary, genital, perineal, intergluteal, and inframammary areas. Because of the moist nature and skin on skin surfaces, the plaques are typically thinner and with minimal to no scale; topical regimens need to be selected carefully for these areas.

Guttate psoriasis occurs in less than 2% of patients with psoriasis and typically found on the trunk and proximal extremities. It is characterized by very small, 1 to 10 mm salmon-pink papules with fine overlying scale (Figure 2). This form of psoriasis is typically preceded by an upper respiratory infection with group A beta-hemolytic streptococcal infection that occurs 2 to 3 weeks prior to the outbreak; as a result, a history of sore throat, cervical lymphadenopathy, fever, headache, generalized malaise, nausea, vomiting, abdominal pain, or stuffy nose should be elicited. Other sites of a streptococcal infection may also trigger guttate psoriasis, such as perianal streptococcal disease in children.

Figure 2.

Clinical picture of guttate psoriasis.

Nail unit psoriasis or psoriatic onychodystrophy can occur with all types of psoriasis or be the sole feature of psoriasis. Approximately 50% of all patients who have psoriasis will have fingernail involvement, and approximately 35% of patients will have toenail involvement. Typical changes include nail pitting, onycholysis (separation of the nail plate from the nail bed), subungual debris, and oil-drop discoloration.

To diagnose psoriasis, often the characteristic clinical appearance and distribution of lesions is all that is necessary. In difficult cases or to confirm the diagnosis, a skin biopsy can be used. Classic histopathologic findings include psoriasiform epidermal hyperplasia, parakeratosis with intracorneal neutrophils, hypogranulosis, a neutrophilic and lymphocytic infiltrate in the epidermis and dermis, and increased dermal papillary vessels.

Expected results of diagnostic studies

No routine laboratory investigation is necessary to diagnose psoriasis, but may be necessary to initiate certain therapeutic interventions. In cases of guttate psoriasis, a culture from the throat for group A streptococcal organisms or checking an ASO titer may be beneficial to confirm a preceding infection.Š In patients with psoriasis, imaging studies of their joints, including sacroiliac, may be necessary if they complain of arthritic symptoms, as psoriatic arthritis may be present. Genetic testing is not routinely offered, although certain HLAŠassociations are known to increase risk.

Diagnosis confirmation

The differential diagnosis of psoriasis includes

1. Seborrheic dermatitis (also characteristically affects the scalp, typically with finer scale but may be difficult to completely differentiate and the term sebopsoriasis may be used; if classic plaque psoriasis is present on rest of exam, then this would confirm psoriasis as the diagnosis

2. Dermatophytoses (distinguished by positive identification on potassium hydroxide (KOH) examination, extent of disease, thicker plaques typically seen in psoriasis)

3. Cutaneous lupus erythematosus, specifically subacute cutaneous lupus erythematosus (distinguished by skin biopsy and characteristic distribution of skin lesions; lupus is worsened with exposure to sunlight while psoriasis typically improves with exposure to light)

4. Atopic dermatitis (characteristically affects flexural surfaces and is eczematous in appearance as opposed to papulosquamous)

5. Pityriasis rosea (both are papulosquamous diseases but pityriasis rosea typically has a herald patch, self-resolves, and classically involves a “Christmas tree” pattern on trunk of individual)

6. Lichen simplex chronicus (differentiated by extent of involvement, clinical appearance, and preceding history), and secondary syphilis (diagnosed based upon positive rapid plasm reagin (RPR) or fluorescent treponemal antibody-absorbed test (FTA-abs), thinner plaques without silvery scale, and presence of plasma cells on skin biopsy or positive spirochetes identified)

7. Cutaneous T-cell lymphoma (usually with more wrinkled, thinner scale and different anatomic location but important to biopsy when diagnosis is in doubt, especially if biologic therapies are to be initiated). Often, the classic characteristic appearance of psoriasis can differentiate between these other entities.

Who is at Risk for Developing this Disease?

Psoriasis has been diagnosed in approximately 2.6% of individuals in the United States, which amounts to approximately 5 million adults with psoriasis. Peak onset of the disease is roughly bimodal, most often at ages 16 to 22 and then ages 57 to 60; however, the disease can occur at any age. Guttate psoriasis is most commonly seen in individuals younger than 30 years.

Risk factors ultimately resulting in the initial presentation of psoriasis or worsening of psoriasis are poorly understood. Koebnerization (or exacerbation from physical trauma to the skin, including sunburn), preceding streptococcal infection, HIV infection, certain medications (such as beta-blockers, lithium, chloroquine, ACE-inhibitors, terbinafine, indomethacin, and interferon-alpha), cigarette smoking, alcohol consumption, and emotional stress have been cited to increase risk for developing or exacerbating disease.

Family history also may increase the risk for development of disease. Some families appear to have an autosomal dominant pattern of inheritance with varying penetrance, and studies of twin siblings have demonstrated concordant disease in approximately 65 to 70% of monozygotic twins and only 15 to 20% in dizygotic twins. However, the development of psoriasis is multifactorial, resulting from genetic and environmental factors and still poorly understood.

What is the Cause of the Disease?

The exact etiology and pathogenesis is unknown but immunologic, genetic, and environmental factors are all are implicated in the development of the disease.

Etiology

Population studies have demonstrated that the incidence of psoriasis is greater among first-degree and second-degree relatives of patients than among the general population. In addition, genetic mapping studies have identified multiple chromosomal loci linked to the development of disease. Psoriasis susceptibility 1 (PSOR1) on chromosome 6, also known as HLA-Cw6 allele, has been strongly associated with the development of psoriasis (up to a 10-fold increase in risk in the Caucasian population) and associated with early onset disease.

Other genetic loci (PSOR2-PSOR9) and HLA-B13, -B17 also have been associated with psoriasis. However, multifactorial inheritance mechanisms without a genetic component also have not been excluded. Variants in the gene encoding the IL-23 receptor and in the untranslated region of the IL12B (p40) gene also have been identified as indicators of psoriasis risk. While this data is compelling for genetic mechanisms, environmental factors also are known to play a role. These environment factors are outlined above.

Pathophysiology

Psoriasis is a complex inflammatory skin condition with abnormal epidermal keratinocyte differentiation and hyperproliferation. This process appears to be immunologically driven and mediated primarily by T cells in the dermis. In the complex model of disease, the interactions of antigen-presenting cells (APCs) with T cells, as well as cytokines, trigger an immune response. The APCs in the skin interact with T cells, and an unidentified antigen is presented to the T cells, and this interaction, along with multiple co-stimulatory signals, lead to T cell activation and the release of cytokines.

The reactivation of T cells in the skin, and the local effects of cytokines such as tumor necrosis factor, interleukin (IL)-1 beta, and IL10 lead to inflammation, cell-mediated immune responses, and epidermal hyperproliferation. In addition to IL12, IL23 has been recently identified as playing an important role in the establishment of chronic inflammation and in the development of a T helper (Th) cell subset that produces IL-17. These Th17 cells pathway are critically important in the pathophysiology of psoriasis.

Systemic Implications and Complications

There are several comorbities and associated systemic disorders that have been demonstrated to be associated with psoriasis.

Psoriatic arthritis

Psoriatic arthritis is an inflammatory seronegative spondyloarthropathy associated with psoriasis; at least 5%, and as many as 40%, of patients with psoriasis will be affected with arthritis. The prevalence overall in the United States is thought to be estimated to be between 0.1% to 0.25%. On average, cutaneous manifestations may occur for 12 years before the development of joint symptoms. Symptoms can range from mild to severe arthritis and are characterized by morning stiffness, pain, swelling, and tenderness of the joints and surrounding ligaments: dactylitis and enthesitis. The spectrum of psoriatic arthritis ranges from peripheral to axial disease. Hands tend to be involved more frequently than feet.

Patients should be routinely questioned for symptoms of arthritis, and if positive, radiographic studies should be performed. Characteristic radiographic features of psoriatic arthritis include joint erosions, joint space narrowing, bony proliferation, osteolysis, including "pencil in cup" deformity, acro-osteolysis, ankylosis, spur formation, and spondylitis. The course of psoriatic arthritis is variable and unpredictable and can vary from mild and nondestructive to a severe, debilitating, erosive arthropathy. Because psoriatic arthritis can be destructive, disease modifying anti-rheumatic drugs (DMARDs) are necessary and referral and collaboration with rheumatology may be required.

Obesity/Metabolic syndrome

The connection between obesity and psoriasis has been confirmed by multiple large studies. Metabolic syndrome is the combination of obesity, impaired glucose regulation, hypertension, hypertriglyceridemia, and reduced high density lipoprotein, which can lead to an increase risk for cardiovascular disease. The prevalence of metabolic syndrome in hospitalized patients with psoriasis is significantly elevated when compared to those patients without psoriasis. Some hypothesize that obesity may potentiate inflammation of psoriasis and facilitate the development of metabolic syndrome. All psoriatic patients should be counseled on diet, exercise, and management of these comorbidities, as this inflammatory state may be contributing to their disease and can lead to other significant morbidity and mortality.

Cardiovascular disease

There is an increased risk of cardiovascular disease, which is thought to be multifactorial. Often times, patients with psoriasis are overweight, have increased incidence of diabetes, increased incidence of hypertension, and hyperlipidemia. Patients have an increased incidence of myocardial infarction, which may be related to their underlying other comorbidities as well as the medications used to treat the psoriasis. However, after correcting for heart disease risk factors, psoriatic patients have a higher probability of myocardial infarction compared to nonaffected individuals, and there appears to be an increased relative risk seen in younger patients with more severe psoriasis. Increased rates of depression in psoriatic patients also may lead to increased risk of cardiovascular disease.

All patients should be counseled that they are increased risk for cardiovascular disease and they should be advised to promote heart healthy behaviors. In fact, some academic centers have established multidisciplinary centers where patients can be evaluated and more extensively counseled for behavior modification and close monitoring for the development of cardiovascular disease.

Autoimmune diseases: Inflammatory bowel disease

The incidence of Crohn's disease and ulcerative colitis has been reported to be 3.8 to 7.5 times greater in patients with psoriasis than in the general population. The individual susceptibility to all 3 of these diseases has been localized to a similar region of chromosome 16. Patients should have a complete review of symptoms for any abdominal pain, diarrhea, fevers, or blood in the stool. If any of these symptoms exist, then referral to gastroenterology is appropriate.

Multiple sclerosis: Multiple sclerosis has been shown to be linked to psoriasis with a study that demonstrated psoriasis is more likely to occur in families of patients with multiple sclerosis.

Psychiatric illness

Mood disorders and lack of self-esteem are increased in patients with psoriasis. According to a telephone survey, 80% of respondents reported that psoriasis had a negative impact on their lives (self-esteem issues and depression). The prevalence of depression in patients with psoriasis can be up to 60%, and this depression can be severe enough to lead to thoughts of suicide. The psychological and emotional burden of psoriasis can include not only poor self-esteem and depression, but also sexual dysfunction and anxiety. Some studies suggest that treatment of psoriasis may help with emotional disorders resulting from the disease. Clinicians need to consider the psychosocial aspects of disease, and if emotional symptoms warrant further help, then referral to a psychiatrist may be appropriate.

Personal behaviors

The emotional impact of psoriasis also may impact patient’s personal behaviors.

Smoking: Multiple studies have demonstrated an increased prevalence of smoking among psoriatic patients. The increased risk for incident psoriasis applied to both current and past smokers. A study conducted in Utah demonstrated a 37% prevalence of smoking in psoriasis population vs 13% in general population of Utah. In one study, the majority of these patients began smoking prior to the development of psoriasis. However, the exact link between cigarette smoking and psoriasis has not been established.

Alcohol: An increase in the amount of alcohol ingested in psoriatic patients has been established. However, the role that alcohol consumption has in the development of psoriasis still remains uncertain. Alcohol abuse may reflect the underlying psychological burden of disease or may be associated with other associated behaviors. Regardless, excessive alcohol intake most likely negatively impacts mortality. All patients should be questioned regarding their social behaviors, and these issues should be addressed when caring for any psoriatic patient.

Treatment Options

Table I summarizes potential therapies for psoriasis, and the use of these therapies will be dictated by severity of psoriasis (mild vs moderate to severe), patient preference and presentation, and type of psoriasis (see below).

Table I.

Potential therapies for psoriasis
Topical Therapies Systemic Medical Therapies Physical Modalities
AnthralinCalcineurin inhibitors (Tacrolimus/pimecrolimus)Coal tarCorticosteroids with or without occlusionSalicylic acidTazaroteneVitamin D analogues (calcipotriene/calcipotriol)*Combination of above therapies also can be used MethotrexateAcitretinCyclosporineTumor necrosis factor (TNF) alpha inhibitors:AdalimumabEtanerceptInfliximabUstekinumabAlefaceptSecond-line (lower quality evidence):AzathioprineFumaric acid estersHydroxyureaLeflunomideMycophenolate mofetilSulfasalazineTacrolimus6-Thioguanine Phototherapy:Narrowband ultraviolet (UV)B/Excimer LaserPsoralen plus UVA (PUVA)Broadband UVB

Optimal Therapeutic Approach for this Disease

If risk factors such as smoking, obesity, alcohol use, diabetes, hypertension are present, counseling and efforts should be made to help the patient with these comorbidities. For patients with joint pain, referral to rheumatology should be sought.

Topical therapies are appropriate for patients with mild or limited disease but are not practical for patients with more significant disease.

Mild psoriasis or limited disease

For mild psoriasis or limited disease, (total body surface area less than 5%), topical therapies are the cornerstone of treatment. They can be used both intermittently and on a long-term basis.

Topical corticosteroids and vitamin D analogues are considered first-line therapies for limited disease. Vitamin D analogues have no apparent risk for atrophy or thinning of skin and may be better used for intertriginous areas.

Topical corticosteroids are the mainstay of treatment for limited psoriasis. For continuous, long-term use, the least potent agent should be used. The efficacy of steroids is determined by the vehicle, area of usage, use of occlusion, unique degree of potency of the topical steroid.

-The best modality to use is the one that the patient will use.

-Lower potency corticosteroids (such as hydrocortisone 2.5% cream or ointment) should be used for limited time periods on the face, intertriginous areas, elderly skin that is thin, and infants. Once to twice daily dosing can be used.

-Higher potency corticosteroids are often required for thick, chronic plaques. Mid-potency steroids (such as triamcinolone 0.1% ointment) are often used on the trunk and extremities as maintenance therapy. For class I corticosteroids (such as clobetasol ointment/cream), data suggest 2 to 4 weeks of use at a time is safe, minimizing the risk of cutaneous side effects and systemic absorption. Once to twice daily dosing can be used. When feasible, a patient should be switched to a less potent topical steroid to further minimize the risks of use.

Vitamin D analogues (calcipotriol or calcipotriene): Calcipotriene cream and calcipotriene/betamethasone proprionate ointment can be used to treat limited psoriasis and in combination with systemic therapies for more severe disease.Š

-Calcipotriene can be inactivated by UVA, so it is important to apply it after UVA exposure. Once to twice daily dosing can be used.

Topical calcineurin inhibitors (tacrolimus and pimecrolimus): TheseŠare efficacious for treating psoriasis on the face and intertriginous areas, especially as a steroid sparing agent.Š These topicals can lead to burning and itching that resolves with ongoing usage. A "black box" warning exists because of lack of long-term safety data and potential risk for development of malignancies; although no clinical evidence to date has demonstrated causality. Once to twice daily dosing can be used.

Topical tazarotene: ThisŠcan be used as a topical agent for psoriasis, although local irritation is the most limiting factor with its use. Short contact orŠonce to twice daily dosing can be used.Š

Topical salicylic acid (typically 6%): As a topical keratolytic, this topical is often combined with other topical therapies including topical corticosteroids and topical tacrolimus. Shampoos with salicylic acid exist to help with scalp psoriasis. Caution for systemic toxicity should exist when used on more than 20% body surface area, as this can result.

Topical anthralin: Topical anthralin is available as a 1% cream and can be used as an antiinflammatory and anti-proliferative medication in short contact.Š This medication was typically used in the past in the inpatient setting, but other topicals that are cosmetically more acceptable have largely replaced it.

Coal tar: This is available in shampoo, solution, and ointment formulation and was used as part of the modified Goeckerman formula of combining topical tar with phototherapy.Š Adverse effects include acne, folliculitis, staining.Š Coal tar 1% lotion is recommended over 5% extract.

Extensive psoriasis

For extensive psoriasis,Š(total body surface areaŠgreater than 5%), systemic therapies or phototherapy are often necessary to control disease.Š All therapies can be considered for any patient with psoriasis, although certain factors or patient situations may dictate or eliminate the use of some therapies.

-Does the patient have psoriatic arthritis? If yes, then a systemic anti-TNF agent, methotrexate, or other disease-modifying antirheumatic drug (DMARD) may be necessary and coordination with rheumatology should occur.

-Does the patient drink alcohol? If yes, then methotrexate cannot be used

-Does the patient have palmoplantar psoriasis? If yes, then acitretin may be considered first-line therapy.

-Does the patient have difficulty with transportation or getting to and from clinics? If yes, then phototherapy should not be considered first.

-Does the patient have a significant history of melanoma or nonmelanoma skin cancer? If yes, then exercise caution with regard to phototherapy, and acitretin is preferred for its protective effect.

-Does the patient have severe psoriasis or is erythrodermic? If yes, then consider cyclosporine as first line with transition to alternate therapy.

-Does the patient have a history of multiple sclerosis or family history of multiple sclerosis or other demyelinating disease? If yes, then TNF alpha-inhibitors should be avoided if feasible.

Suggested order of therapies for specific types of psoriasis (if applicable)

Palmar-plantar psoriasis:

First-line therapies: Acitretin, topical PUVA therapy, adalimumab

Second-line therapies: alefacept, etanercept, infliximab, methotrexate, cyclosporine, ustekinumab

Guttate psoriasis:

First-line therapies: topical therapy if limited number of lesions; UVB phototherapy if involvement is extensive

Second-line therapies: short-term cyclosporine or methotrexate

Third-line therapies: TNF inhibitors (prefer to avoid given risk of loss of efficacy if stopped and need to be utilized if flares again in future)

Inverse psoriasis:

First-line therapies: topical agents, including topical calcipotriol and calcineurin inhibitors as steroid-sparing agents as well as low potency topical steroids

Second-line therapies: systemic agents; targeted UVB phototherapy

--Phototherapy less optimal given location of psoriatic plaques

Details about individual therapies

Methotrexate: May be used as solo therapy orŠin conjunction with TNF alpha-inhibitors to prevent antibody formation to the biologic agents.

-Initial test dose of 2.5 or 5mg once and then increase to 15-25mg weekly as tolerated. May be dosed orally, intramuscularly, or subcutaneously.

-Expect 3 months for full effect to be appreciated at optimal dose.

-Monitor: baseline CBC, CMP, hepatitis B and C, HIV; follow-up with CBC and LFT every week for 2 weeks, then every 3--4 months.

When discussing and treating any patient with psoriasis,explain the natural history of psoriasis, with an explanation that this is a chronic condition that will not be cured but can be controlled and that therapies often need 3 months to determine efficacy. If patients are not tolerating therapy or do not respond within the expected period of time, then an alternate therapy should be sought. If patientsdevelop arthritis, then a systemic medication should be considered to help with arthritis if the patient is not on one.

Patients should be monitored for any evidence of systemic infections, arthritis symptoms, underlying malignancies on a regular basis.Š Patients also should be counseled about for heart-healthy behaviors, smoking cessation, or reduction in alcohol consumption, and screened for depression/anxiety.ŠPatients should also be encouraged to maintain as close to an ideal body weight as is possible.

Depending on the medication that patients are on, they should be monitored as outlined above.

All therapies have risks and benefits that need to be closely considered.

If patients are clear from their disease, then drug holidays may be considered, especially with treatments such as topical medicines, phototherapy, methotrexate, or acitretin. This is more difficult with systemic biologic therapies, as antibodies with resistance may develop to these therapies, rendering them ineffective.

For biologic and immunosuppressant medications:

-Patients hould be periodically reevaluated for development of new symptoms, including infection and malignancy as well as arthritic symptoms.

-Do not use live vaccines while on these therapies

-Yearly PPD or quantiferon gold medication is necessary

For patients on methotrexate:

-No alcohol consumption is the guideline

-Liver biopsy recommendations: in patients with no risk factors, then liver biopsy may be postponed until a cumulative dose of 3.5-4 g is reached. In those patients with risk factors for liver disease, then earlier liver biopsy may be necessary. Delayed baseline liver biopsy after 2-6 months of therapy to establish medication efficacy and tolerability should be considered, with repeated liver biopsies after approximately 1 to 1.5 g of medication.

-Contraindicated: pregnancy, renal impairment, hepatitis or cirrhosis, alcohol use, leukemia, thrombocytopenia

Acitretin: May be used in monotherapy or combination with UVB or PUVA.Š May be considered first line for palmoplantar psoriasis and erythrodermic psoriasis.

-Dose 10 to 25mg daily or 0.25 mg/kg/day for erythrodermic patients

-Expect 2 months for full effect to be appreciated at optimal dose.

-Monitor: baseline lipids and LFTs; follow-up 2-4 weeks after use, then every 3 months

-Contraindicated: pregnancy, breast-feeding, woman of childbearing potential who may get pregnant within 3 years after discontinuing acitretin (length of time remaining in system)

-Monitor for dyslipidemia

Cyclosporine: Works rapidly and is efficacious for severe psoriasis or erythrodermic psoriasis.Š This medication should be used as a bridging and short-term therapy for 3-4 monthsŠat a time.Š

-Dose 0.5-5mg/kg/day divided into two daily doses.

-Expect a rapid response within 1-2 weeks

-Monitor: baseline blood pressure, CMP, CBC, LFTs, lipid panel, Mg, uric acid; then follow-up with all labs every 2 weeks for 2 weeks, then every month.

-Adverse effects: impaired renal function, hypertension, concern for lymphoma, potential for cutaneous malignancies

Phototherapy: Good for patients with co-morbidities, most types of psoriasis, including guttate psoriasis.Š More difficult to treat inverse psoriasis and scalp psoriasis.

-Contraindicated: underlying lupus erythematosus; xenoderma pigmentosum; porphyria (PUVA); caution with history of nonmelanoma or melanoma skin cancer

-Baseline: check ANA if clinical suspicion exists

NBUVB: Check MED (minimal erythema dose)

-First dose, 70-80% of MED or based upon skin typing with increasing doses based upon response: no erythema, increase by 10-20%; erythema lasting >24 hours but less than 48 hours, same dose; persistent erythema at 48 hours, then postpone treatment followed by lower dose and slower increase of 5-10%; painful: postpone until recovered then decrease dose to less than previously well-tolerated.

-Response may be seen after 8-10 treatments with course of 15-25 treatments three times weekly necessary; after clearing, some patients may be treated with a maintenance regimen of 2-4 times per month.

Targeted NBUVB in form of Excimer laser: Good for patients with limited disease.

-Can be utilized in hard to reach areas such as the scalp and intertriginous areas; it also can also be used on the palms and soles.

MED determined by skin type. Multiple MED’s administered depending on the thickness of the individual lesions. As lesions thin, subsequent doses are lowered until clearing is achieved. Patients should be treated twice weekly. There is no known maintenance option for the laser protocol.

PUVA:Š can be performed with topical (useful for hands/feet) or oral psoralen

-Topical: oxsoralen 0.1% in hydrophilic ointment, applied 15 minutes before light therapy; start 0.25 J and increased by 0.5 J each visit as tolerated

-Oral: 0.6 to 0.8mg/kg of 8-methoxypsoralen 1 to 1.5 hours prior to exposure; initial dose based on skin type with increasing dose as tolerated. Dose increments based on skin type ranging from 0.5J-1.0 J/Rx as tolerated.

-Treatments occur 2-3 times per week; after clearing, some patients may be treated with a maintenance regimen ranging from once weekly to once every sixth week depending on skin type and tolerability.

-Number of treatments: clearing of psoriasis after about 24 treatments with remissions lasting between 3- 6 months.

Biologics:

TNF-alpha inhibitors:

-Monitoring: baseline CBC, LFT, hepatitis, HIV, and PPD or quantiferon gold test; CBC and CMP every 3-6 months thereafter and PPD quantiferon gold test yearly thereafter.

-Contraindicated: patients with multiple sclerosis or other demyelinating diseases; caution with those with first-degree relatives with multiple sclerosis as they may have an increased risk of developing the disease; active infection, including tuberculosis; congestive heart failure with New York Heart Association class III or IV or ejection factor <50%

-Time to efficacy: 12 weeks

Adalimumab:

-Dose is 80 mg the first week, 40 mg the second week, then 40 mg every other week (given subcutaneously)

Etanercept:

-Dose 50 mg twice weekly for 3 months, then 50 mg weekly (given subcutaneously)

Infliximab:

-Dose is 5mg/kg dose infusion at weeks 0, 2, and 6, and then every 6-8 weeks (with adjustment in intervals as needed for intravenous infusion)

Ustekinumab:

-Dose: <100 kg, then 45 mg; for >100 kg, then increase dose to 90 mg; both subcutaneously at 0 and 4 weeks, then every 12 weeks.

-Time to efficacy: 12 weeks

-Monitor: baseline CBC, CMP, PPD or quantiferon gold test, HIV test, hepatitis B; yearly PPD or quantiferon gold test; CBC and CMP every 3-6 months thereafter.

Secukinumab:

-Dose: 150 mg or 300 mg at weeks 0,1,2,3,4, then every 4 weeks thereafter

Time to efficacy: 16 weeks, but can be seen more rapidly

Monitor: baseline CBC, CMP, PPD or quantiferon gold test, HIV test, hepatitis B; yearly PPD or quantiferon gold test; CBC and CMP every 3-6 months thereafter

Apremilast:

-Dose: 10 mg daily escalating to 30 mg twice daily as follows:

Šday 1: 10 mg daily

Šday 2: 10 mg twice daily

Šday 3: 20 mg q AM, 10 mg q PM

Šday 4: 20 mg twice daily

Šday 5: 30 mg q AM, 20 mg q PM

Šday 6: 30 mg twice daily

Dose can be advanced more slowly to further reduce risk of GI side effects

Dose should be halved in setting of severe renal impairment

Time to efficacy: 16 weeks

Monitor: none required

Potential side effects: depression, weight loss, possible interaction with cytochrome P450 inducers (such as rifampin)

Second-line therapies

Due to treatment failure or resistance, it is occasionally necessary to use alternate therapies for psoriasis. There is less evidence supporting the use of the following agentss compared with the therapies listed above/the more common therapies.

Azathioprine

Fumaric acid esters

Hydroxyurea

Leflunomide

Mycophenolate mofetil

Sulfasalazine

Tacrolimus

6-Thioguanine

Patient Management

When discussing and treating any patient with psoriasis, explain the natural history of psoriasis, also explaining that that this is a chronic condition that will not be cured but can be controlled and that therapies often need 3 months to determine efficacy. If patients are not tolerating therapy or do not respond within the expected period of time, then an alternate therapy should be sought. If patients develop arthritis, then a systemic medication should be considered to help with arthritis if the patient is not on one.

Patients should be monitored for any evidence of systemic infections, arthritis symptoms, underlying malignancies on a regular basis. Patients also should be counseled about for heart healthy behaviors, smoking cessation or reduction in alcohol consumption, and screened for depression/anxiety. Patients should also be encouraged to maintain as close to an ideal body weight as is possible.

Depending on the medication that patients are on, they should be monitored as outlined above.

All therapies have risks and benefits that need to be closely considered.

If patients are clear from their disease, then drug holidays may be considered, especially with treatments such as topical medicines, phototherapy, methotrexate, or acitretin. This is more difficult with systemic biologic therapies, as antibodies with resistance may develop to these therapies, rendering them ineffective.

For biologic and immunosuppressant medications:

-Patient should be periodically re-evaluated for development of new symptoms including infection and malignancy as well as arthritic symptoms.

-Do not use live vaccines while on these therapies

-Yearly PPD or quantiferon gold medication is necessary

For patients on methotrexate:

-No alcohol consumption is the guideline

-Liver biopsy recommendations: in patients with no risk factors, then liver biopsy may be postponed until a cumulative dose of 3.5-4 g is reached. In those patients with risk factors for liver disease, then earlier liver biopsy may be necessary. Delayed baseline liver biopsy after 2-6 months of therapy to establish medication efficacy and tolerability should be considered, with repeated liver biopsies after approximately 1 to 1.5 g of medication.

Unusual Clinical Scenarios to Consider in Patient Management

Pediatric population

Often topical therapies are sufficient to manage children’s disease. Caution should be used with topical corticosteroids in order to prevent skin atrophy in these patients.

For treatment-resistant or severe disease, systemic therapies can be considered. For older children, limited courses of phototherapy eliminate some of the side effects associated with using systemic immunosuppressants.

Methotrexate and cyclosporine have been used to safely control disease in children; close monitoring should be employed. Oral retinoids (acitretin and related compounds)Šhave been used safely and successfully in children; long-term exposure can lead to premature epiphyseal closure and impaired growth.Š It also is absolutely contraindicated in pregnancy and in reproductive years, unless contraception during and for 3 years after therapy cessation is employed.

Biologic therapies are not approved for use in children, although etanercept has been the best studied for psoriasis in pediatric population with overall good safety and isolated cases of severe infection.

Pregnancy

During pregnancy, special care must be used due to potential teratogenic effects of commonly used treatments. Often, psoriasis may improve during pregnancy due to hormonal changes.

--Absolutely contraindicated, category X: methotrexate, acitretin, topical tazarotene

--Category C: topical corticosteroids, topical calcipotriene, calcineurin, anthralin, cyclosporine, PUVA due to psoralens

--Category B: systemic biologic agents; however, there is a relative lack of data regarding the safety of these medications in pregnancy in patients with psoriasis

--NBUVB, broad band UVB: considered the safest treatment for severe psoriasis during pregnancy

Nursing mothers

The safest therapy is NBUVB. Topical corticosteroids and topical calcipotriene also considered safe. Methotrexate is contraindicated

Male partners of females trying to get pregnant

Methotrexate is contraindicated as it can lead to oligospermia, although no fetal malformation has been demonstrated.. Conception should be delayed for 3 months after methotrexate use. With rspect to use of systemic retinoids: it is unknown if the teratogenic risk extends to children of male partners treated with acitretin but the risk is thought to be minimal.

Hepatitis B

Methotrexate should not be prescribed due to hepatotoxicity. Because hepatitis B reactivation has been observed in patients undergoing therapy with TNF alpha-inhibitors and ustekinumab, screening for hepatitis B should occur prior to initiation of therapy. In hepatitis B positive individuals with inactive disease, a course of antivirals for 2-4 weeks should be initiated prior to anti-TNF therapy. At this time, it is unknown if treatment with antivirals makes use of ustekinumab safe in this population.

Hepatitis C

Methotrexate should not be used due to hepatotoxicity.

-There is a relative lack of data regarding treatment of psoriasis in patients with hepatitis C, but UVB phototherapy is felt to be safe in this setting and considered first-tline therapy if feasible. Etanercept may act as an adjuvant to standard antiviral therapy in treating hepatitis C. Adalimumab, infliximab, and ustekinumab have been less well studied, but probably may be utilized in this clinical setting as well. Cyclosporine also may be a treatment option in this patient population as in vitro evidence suggests that cyclosporine suppresses the replication of the hepatitis C virus.

HIV

The primary treatment is that of underlying HIV itself with anti-retrovirals. Phototherapy is considered a first-line systemic agent for treatment of psoriasis in this patient population.

Topical therapies also should be used first-line, although they typically are of limited success given the extent of involvement in this patient population. Acitretin is considered a second line systemic therapies; caution with hyperlipidemia with acitretin and other antiretrovirals should be used. For more refractory and severe disease, extremely cautious use of systemic immunosuppressants such as methotrexate, cyclosporine, or biologic therapies may be considered with collaboration with infectious disease specialists; however, these should be rarely used.

What is the Evidence?

Gottlieb, A, Korman, NJ, Gordon, KB, Feldman, SR, Lebwohl, M, Koo, JY. "Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics". J Am Acad Dermatol. vol. 58. 2008. pp. 851-64.

(Great overview on treatment guidelines provided based on evidence and then consensus statement by AAD.)

Kalb, RE, Bagel, J, Korman, NJ, Lebwohl, MG, Young, M, Horn, EJ. "Treatment of intertriginous psoriasis: from the Medical Board of the National Psoriasis Foundation". J Am Acad Dermatol. vol. 60. 2009. pp. 120-4.

(Consensus guidelines that were put together by the National Psoriasis Foundation that reviews pertinent therapies.)

Kimball, AB, Gladman, D, Gelfand, JM, Gordon, K, Horn, EJ, Korman, NJ. "National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening". J Am Acad Dermatol. vol. 58. 2008. pp. 1031-42.

(AAD consensus for psoriasis comorbidity screening.)

Lebwohl, M, Bagel, J, Gelfand, JM, Gladman, D, Gordon, KB, Hsu, S. "From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis". J Am Acad Dermatol. vol. 58. 2008. pp. 94-105.

(Overview on the use of biologics, including laboratory monitoring and vaccinations necessary when using biology therapies from the National Psoriasis Foundation.)

Menon, K, Van Voorhees, AS, Bebo, BF, Gladman, DD, Hsu, S, Kalb, RE. "Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation". J Am Acad Dermatol. vol. 62. 2010. pp. 291-9.

(Overview of treatment strategies for HIV-associated psoriasis from the National Psoriasis Foundation.)

Menter, A, Gottlieb, A, Feldman, SR, Van Voorhees, AS, Leonardi, CL, Gordon, KB. "Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics". J Am Acad Dermatol. vol. 58. 2008. pp. 826-50.

(AAD guidelines for biologic treatment of psoriasis. Guidelines published by the AAD on the overview of treatment of psoriasis and psoriatic arthritis; first section in a series of articles.)

Menter, A, Korman, NJ, Elmets, CA, Feldman, SR, Gelfand, JM, Gordon, KB. "American Academy of Dermatology. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies". J Am Acad Dermatol. vol. 60. 2009. pp. 643-59.

(Paper reviewing the guidelines from the AAD on topical therapies for psoriaisis that provides information on risks and benefits as well as combination therapy for this.)

Menter, A, Korman, NJ, Elmets, CA, Feldman, SR, Gelfand, JM, Gordon, K. "Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents". J Am Acad Dermatol. vol. 61. 2009. pp. 451-85.

(Overview on the management of psoriasis when using AAD guidelines for use of systemic agents (nonbiologics) in psoriasis.)

Menter, A, Korman, NJ, Elmets, CA, Feldman, SR, Gelfand, JM, Gordon, KB. "Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy". J Am Acad Dermatol. vol. 62. 2010. pp. 114-35.

(Review of treatment options for use of phototherapy for psoriasis.)

Rosenbach, M, Hsu, S, Korman, NJ, Lebwohl, MG, Young, M, Bebo, BF. "Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation". J Am Acad Dermatol. vol. 62. 2010. pp. 655-62.

(AAD guidelines for treatment of erythrodermic psoriasis. Overview of treatment options and management of erythrodermic psoriasis.)

Kalb, RE, Fiorentino, DF, Lebwohl, MG. "Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR)". JAMA Dermatol.

Langley, RG, Elewski, BE, Lebwohl, M. "Secukinumab in plaque psoriasis—results of two phase 3 trials". N Engl J Med.

Thaci, D, Blauvelt, A, Reich, K. "Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized, controlled trial". J Am Acad Dermatol.

Paul, C, Cather, J, Gooderham, M. "Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis over 52 weeks: a phase III, randomized, controlled trial (ESTEEM 2)". Br J Dermatol.

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