787.full

CLINICAL REVIEW

Psoriasis Vulgaris: An Evidence-Based Guide forPrimary CareErine A. Kupetsky, DO, MSc, and Matthew Keller, MD

Psoriasis vulgaris is a chronic, sometimes debilitating, inflammatory disorder with multiple pathways ofpathogenesis that can be associated with metabolic and cardiovascular disease. This article aims to be acomprehensive, literature-based review of the epidemiology, genetic factors, clinical diagnosis, treat-ments, and pharmacology for psoriasis as derived from articles published in PubMed. Levels of evi-dence and recommendations were made according to the strength of recommendation taxonomy. Thisarticle is divided into 2 sections: the first is clinical and diagnostic, the second is therapeutic. This re-view serves as a practical, evidence-based, and unbiased guide for primary care practitioners. (J AmBoard Fam Med 2013;26:787–801.)

Keywords: Dermatology, Primary Health Care, Psoriasis, Skin Diseases

Psoriasis is a chronic inflammatory disease thataffects up to 5% of the world’s population.1 Cur-rent estimates put the prevalence of psoriasis at upto 7.5 million cases in the United States. It is morecommon in whites and those who live farther fromthe equator, and it is equally common in men andwomen.2 Psoriasis is more common with certainhuman leukocyte antigen (HLA) subtypes, butthese cannot be distinguished histologically or clin-ically and there is no apparent difference in theresponse to therapy.2 Psoriasis can generally bedivided into 2 types: Type 1 psoriasis shows astrong family history for the disease, demonstratesan association with HLA-CW6,3 and usually pres-ents before 40 years of age.2 Type 2 is not familialin presentation, has no association with HLA-CW6,3 and usually presents after 40 years of age.2

MethodsThe literature published in PubMed from 2000 to2012 was searched using the following key words:psoriasis, treatments, clinical trials, and reviews. Ab-stracts were included only if they were clinicallyrelevant; the articles were downloaded as portabledocument files. The first author (EAK) performedthe literature search, captured and processed thearticles, and determined the strength of recommen-dation taxonomy (SORT) criteria with level of ev-idence (1–3).4

DiagnosticsTable 1 describes the pathogenesis of psoriasis, andTable 2 lists risk factors and comorbidities that cancontribute to the development of moderate or se-vere psoriasis. The diagnosis of psoriasis can bedetermined clinically (Table 3) and histologically, ifneeded. Before treatment for psoriasis can be ini-tiated, the grading and severity must be determined(Table 4).

Topical TreatmentsTopical Corticosteroids (SORT CriteriaRecommendation A, Level of Evidence 1)Dosing and Side EffectsChoosing the strength of topical steroids and vehi-cle of administration is important in order to obtainthe most benefit with the least potential for side

This article was externally peer reviewed.Submitted 6 February 2013; revised 27 July 2013; accepted

12 August 2013.From the Department of Dermatology and Cutaneous

Biology, Thomas Jefferson University, Philadelphia, PA.Funding: none.Conflict of interest: none declared.Corresponding author: Erine A. Kupetsky, DO, MSc, De-

partment of Dermatology and Cutaneous Biology, BluemleLife Sciences Building, 233 South 10th Street, Suite 450,Philadelphia, PA 19107 (E-mail: [email protected]).

doi: 10.3122/jabfm.2013.06.130055 Psoriasis Vulgaris 787

mailto:[email protected]

effects. It is possible to treat the majority of patientsif a physician has a good grasp on the use of just 3classes of steroids: superhigh potency (class I), mid/high potency (class III), and low potency (class VI).Steroids should be used with caution on the face,

groin, axilla, and breasts because these areas aremore sensitive to topical steroid penetration andcan develop striae.15 The usual dosage for topicalsteroids is twice per day for 2 weeks, but this canrange depending on the severity and location of thepsoriasis and the strength of the steroid used. Forexample, a superpotent steroid limited to �5%body surface area can be used twice daily for up to2 weeks on the body but avoiding the face andintertriginous regions. Atrophy, telangiectasia, andstriae15 are always a concern, especially when top-ical steroids are used for long periods of time orused on the groin, axilla, or under occlusion.

VehiclesTopical steroid compounds come in various vehi-cles, which can determine the area of application,level of efficacy, and possible side effects. Lotionsare water-based, weakest in strength, and evapo-rate. Shampoos may be used for psoriasis on thescalp but limited contact time limits efficacy, mak-ing solutions and sprays more effective for thescalp. Gels are alcohol-based, evaporate quickly,and sting but are equipotent with ointments andsolutions. Many patients prefer gels because theyare easy to apply and do not stain clothing. Oint-ments are petrolatum-based, typically the most po-tent, and usually do not irritate, making them thebest option for sensitive skin. Foams contain alco-hol and therefore evaporate quickly, which makethem appropriate for application in the hair or forpatients (especially men) who prefer this clean typeof vehicle. Creams are lipid-based and do not evap-

Table 1. Pathogenesis of Psoriasis

Pathway Producer Action in Psoriasis

TNF-� (overexpressed inpsoriasis)5

Macrophages, T cells, mast cells,granulocytes, natural killer cells,fibroblasts, neurons,keratinocytes, and smoothmuscle cells5

Increases the release of cytokines by lymphocytes and chemokinesby macrophages6

Increases expression of adhesion molecules attracting neutrophilsand macrophages to the lesions by activation of the vascularendothelium6

Induces keratinocyte and endothelial cell neovascularizationstimulating the inflammatory process6

IL-12/23(upregulatedin psoriasis)7

IL-12 promotes the differentiation of naive CD4� T lymphocytesto Th1 cells.7

IL-12 triggers the specialization of CD4 and CD8 T lymphocytesby major histocompatibility complex class I and II, respectively,via antigen-presenting cells, which convert CD4� cells into Thcells and CD8� into cytotoxic T cells.6 As a result, TNF- �,IL-2, interferon-�, and other cytokines are produced.6

Th17 Th17 cells produce IL-17, a potentproinflammatory cytokine

Il-17 directly perpetuates further inflammation of the keratinocyte,but it also indirectly stimulates production of IL-6.8

IL, interleukin; Th, T helper; TNF, tumor necrosis factor.

Table 2. Risk Factors and Comorbidities for Moderateto Severe and Severe Psoriasis2,5,9,10

● Psoriatic arthritis (25% of psoriatics develop PsA2)● Genetic predisposition to autoimmune disease● TNF-� deregulation● Elevated C-reactive protein increases risk of diseases like

Crohn’s, multiple sclerosis, cardiovascular disease(myocardial infarction and stroke), depression, andlymphoma (compared to the nonaffected age- and sex-matched population)*

● More likely to smoke● Have HTN● Have diabetes, obesity, and hypercholesterolemia● Even when corrected for above risk factors

(hypercholesterolemia, diabetes, HTN, and obesity),patients with severe psoriasis have an elevated incidence ofmyocardial infarction compared with age-matched patientswithout psoriasis2,11

● Control of HTN, cholesterol, weight, and diabetes canassist in decreasing psoriasis burden and frequency of flares2

● Moderate to severe psoriasis is associated with depression,suicide,9 and rarely lymphoma10; this risk increases withdisease burden

*Because of this baseline elevation in inflammatory markers,especially in patients with moderate to severe plaque psoriasis,risk for certain diseases like multiple sclerosis,12 lymphoma,13

and myocardial infarction may be elevated even further with useof a TNF-� blocker.2,10 On the other hand, patients with mod-erate to severe psoriasis with depression and suicidal ideationwho are placed on etanercept, a TNF-� blocker, may improveboth their psoriasis and their depression.9,14

TNF, tumor necrosis factor; HTN, hypertension.

788 JABFM November–December 2013 Vol. 26 No. 6 http://www.jabfm.org

Tabl

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orate as quickly but may sting with application. Ingeneral, anything that is not petrolatum-based willalmost definitely temporarily burn on the skin thatis excoriated or not intact. Most lotions are not truelotions but more along the line of alcohol-basedsolutions.

Classes and CompoundsClass I (superhigh potency) topical steroids in-cludes clobetasol propionate, betamethasone dipro-pionate augmented, and halobetasol propionate.Class III (mid/high potency) includes triamcino-lone acetonide 0.1%, fluticasone propionate, amci-nonide, fluocinonide. Class VI (low potency) topi-cal steroids are alclometasone dipropionate anddesonide. Some pharmacies can “compound” thesesteroids in combination with CeraVe (ValeantPharmaceuticals North America, Bridgewater, NJ)or Cetaphil (Galderma Laboratories, Fort Worth,TX), usually as 1:1. CeraVe and Cetaphil are pre-ferred over Aquaphor or Eucerin (Beirsdorf, Inc.,Wilton, CT) because the latter contain lanolin,which can have chemicals like cetostearyl alcoholand potassium sorbate added during their chemicalpreparation and cause irritation and allergies inthose who are susceptible to it, precipitating a Koe-bner phenomenon.23

Vitamin D Analog Preparations (SORT CriteriaRecommendation A, Level of Evidence 1)Vitamin D analogs inhibit keratinocyte prolifera-tion through increased differentiation of cells andinhibit the accumulation of inflammatory cells.3

Vitamin D analogs can be used alone or in combi-nation with topical steroids (compounded by thepharmacy) or alternating with topical steroids (ap-plied by the patient), acitretin, cyclosporin A (CsA),

or phototherapy. Calcipotriene 0.005% cream,ointment, and scalp solution 0.005% are availablefor use twice a day. Calcipotriene is also is availablecombined with betamethasone dipropionate 0.064% inan ointment and suspension. The maximum dosefor these is 100 g/week. Calcitriol 3 �g/g ointmentis also available, to be applied twice daily. Themaximum exposure to this drug is 200 g/week be-cause of the risk of hypercalcemia and hypercalci-uria. Vitamin D analogs can be applied 2 hoursafter ultraviolet (UV) light therapy, but they shouldnot be applied before UV therapy since they areinactivated by UV light.24 The most common re-action is irritation at the site of application, whichlimits its use on the face and intertriginous areas. ACochrane review published in 2011 showed thatthe compounded vitamin D analog calcipotrieneand betamethasone dipropionate was more effec-tive for long-term treatment of mild to moderatepsoriasis than using either drug alone.25

Topical Calcineurin Inhibitor (SORT CriteriaRecommendation A, Level of Evidence 2)The topical calcineurin inhibitors tacrolimus 0.1%ointment and pimecrolimus 1.0% cream are avail-able. They are applied twice daily and mostly usedfor disease on the face and intertriginous areas, forinverse psoriasis, or used anywhere on the body asa steroid-sparing or maintenance therapy.26,27

There has been no evidence of skin atrophy orabsorption by the body.3 It is important for theprimary care physician (PCP) to become familiarwith the “black box” warning from the US Food anDrug Administration as well as articles refuting theuse of these inhibitors, which found 20 case reportsof lymphoma and 10 cases of skin neoplasms world-wide after treatment with these drugs, but no causalrelationships were verified.28 These preparationsare off-label, generally safe, and are recommendedfor use in children �2 years old.

Ultraviolet Light (SORT Criteria Recommendation B,Level of Evidence 2)Using UV light is probably one of the safest andoldest modalities for the treatment of psoriasis.Historically, the combination of dead sea salts,which are rich in anti-inflammatory mediators,with irradiation, called heliotherapy, was and isuseful for the treatment of many skin and rheu-matic conditions.29 In general, UV light works bydecreasing keratinocyte proliferation and has anti-

Table 4. Psoriasis: Severity Grading19

Psoriasis BSA* (%) Treatment Required

Mild �5 TopicalModerate to severe† 5–10 Topical and systemicSevere �10 Systemic

*To determine a patient’s body surface area (BSA) of plaqueinvolvement, the doctor would use the patient’s own palmarhandprint as a guide while they perform their examination. Thesurface area for each handprint is equal to 0.8% of the total BSAfor men,21 0.7% for women, and 0.94% for children.22

†Severe disease: significant involvement of the palms/soles, faceor intertriginous areas as these may be significantly debilitating.


inflammatory properties.3 As an anecdote, the rec-ommendation for patients with psoriasis who areusing natural light should try to achieve only 5 to10 minutes spent unprotected in the mid-day sun 3times per week. Some PCPs who see a large num-ber of dermatologic cases may own a light box orsend patients to a hospital-based light therapy cen-ter. UV light therapy can be used in combinationwith certain systemic (eg, methotrexate and aci-tretin) and topical medications (eg, topical ste-roids or calcipotriene); however, timing of theapplication of topical steroids and tapering thedose of UV therapy to avoid burning are factorsto consider. The current consensus is that nar-rowband UVB light is better than broadbandUVB light and is considered first-line treatmentfor extensive plaque psoriasis, especially if theplaques are thin and the patient is young.30 –32

UV therapy is also effective for psoriasis of thepalms and soles or guttate psoriasis. Althoughtreatments vary, doses of UV therapy generallyare administered 3 times per week for a minimumof 3 months.30 Psoralen plus UVA is useful forpsoriasis of the hands and feet, in cases wherenarrowband UVB light fails, or for plaques thatare too thick for light to penetrate.33 The risks ofUV use are burning and skin cancer risk, butthese are more common with the use of Psoralenplus UVA, so routine full skin examinations arerecommended.30

Intralesional Corticosteroid TriamcinoloneAcetonide 2.5 to 10 mg/mL (SORT CriteriaRecommendation C, Level of Evidence 3)Intralesional injections are an effective method todeliver a small amount of corticosteroid to anarea of psoriasis. In the case of nail psoriasis,injecting the proximal nail fold to target theproximal nail matrix reduces nail inflammation.34

Using a fine-gauge insulin needle that will notpop off is recommended. The decision ofwhether to use anesthesia depends on the patient;however, injecting the deep proximal nail fold orthe nail bed to target subungual hyperkeratosisor onycholysis will require initial anesthesiablock.34 In mild psoriatic disease, where 1 or 2plaques are resistant to topical treatments, forexample, intralesional steroids may play a role.Skin atrophy is a concern with this modality; toavoid this, the lowest effective dose of triamcin-olone acetonide (3–5 mg/mL) should be used.

These procedures are painful for the patient,especially injection of the nail bed. Injectionsshould be limited to no more than 6 to 8 weeksapart and given only if necessary.

It is important to note that there are rare cir-cumstances in which oral corticosteroids are pre-scribed for psoriasis. In all cases, the benefits shouldoutweigh the risks. Abrupt discontinuation can pre-cipitate an erythrodermic reaction, a flare-up ofpustular psoriasis, or simply a significant reboundflare of classic psoriasis.

Anthralin (SORT Criteria Recommendation C, Levelof Evidence 3)Anthralin is a man-made version of a natural sub-stance found in goa powder, which is from theararoba tree and functions by slowing the growth ofkeratinocytes. It can be used with caution in bothchildren and adults because it can cause contactdermatitis if left on too long or if rubbed in the eyesor on the genital area.35 Anthralin is usually left onfor 5 to 20 minutes then washed off to avoid browndiscoloration of clothing. Anthralin can be com-pounded with salicylic acid for stability.35

Systemic TreatmentsSystemic treatments used to treat psoriasis are sum-marized in Table 5.

Biological Drugs (SORT Criteria Recommendation A,Level of Evidence 1)Screening before Administration of Biologic TherapyBefore starting a patient on any biologic drug,much needs to be assessed by a history and physicalexamination, laboratory tests have to be analyzed(see Tables 6 and 7), and a closer follow-up must beconsidered. Though mostly well tolerated withoutsignificant side effects and because of the extensivefollow-up required with their use, many PCPs willuse biologics, working in conjunction with derma-tologists who are familiar with their use. Drugallergies and current medications (dermatologicaland others) should be assessed, looking for thosemedicines that may increase immunosuppression ormay exacerbate the psoriasis.2 In addition, a pa-tient’s medical history should be carefully evaluatedand medicine regime reconciled to ensure that ifthe patient were to start taking a biologic drug,there would be as few interactions as possible. Forexample, reports of hypoglycemia in patients taking


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etanercept warrant a reduction of antidiabetic dos-ing and monitoring of glucose logs by PCPs forsome of these patients.36 Because some patientswho have plaque psoriasis have untreated antistrep-tolysin O titers from guttate psoriasis (that devel-oped into plaque psoriasis), it always is a good ideato check an antistreptolysin O titer for every pa-tient with new psoriasis.

VaccinesSince patients taking these therapies may not re-ceive live or live-attenuated vaccines (measles,mumps, rubella; oral polio vaccine; varicella zostervaccine [VZV]; Bacillus Calmette-Guerin; yellowfever; and influenza [nasal]), ensuring that thesepatients are up to date with their age-appropriatevaccines is important. Annual inactivated influenzaand pneumococcal (at least one dose, if necessary)60

vaccines should be given since these biologic drugscan lower the immune system’s ability to fight in-fection. Vaccination for hepatitis A and B also arerecommended before beginning a biologic. It usu-ally takes 2 to 6 weeks for the body to produce asignificant amount of antibodies after immuniza-tion.59

Other RisksLymphoma and Leukemia. Lupus-like symptoms(butterfly sun-sensitive rash, oral ulcers, etc.) canbe a side effect of using tumor necrosis factor(TNF)-� inhibitors.36,55 Some biological drugsalso increase antinuclear antibody titers, so estab-lishing a baseline antinuclear antibody titer is op-tional.59 Biological drugs can also increase the riskof cancer, mostly lymphoma10 and leukemia36,55;however, it is uncertain whether it is the psoriasisor the initiation TNF-� blocking treatment that isthe causative factor.5 According to some studies,many of the original clinical trials conducted usingadalimumab and etanercept in patients with rheu-matoid arthritis, psoriatic arthritis, ankylosing

Table 6. Exclusions for Biological Drugs

Latent TB dx without proper tx36,55,56*Blood dyscrasiaWegener’s granulomatosis36,55

Recent illnessImmunosuppressive diseaseUstekinumab only for drug-induced psoriasis, any history of

malignancy (except for basal or squamous cell carcinomaskin cancer and cervical cancer in situ treated at least 5years before the initiation of ustekinumab), and a historyof active TB (latent, treated TB can receive treatment)7

History of hepatitis, positive hepatitis B (which can bereactivated in chronic carriers, thus, the need for thevaccination), or active or untreated hepatitis C

Multiple sclerosis (except for ustekinumab)Any demyelinating disorder7,36,55

*Patients diagnosed with tuberculosis (TB) who have received atleast 2 months of treatment can receive a tumor necrosis factor(TNF)-� inhibitor with close supervision and a multidisci-plinary approach. TNF-� modulates granuloma homeostasisand contains latent disease.57 In patients with a history of latentTB, indurations on PPD of �5 mm, even with history of BCGvaccination, is considered positive and exclusionary withoutproper treatment for TB.36,55 The risk of TB reactivation islower with etanercept, a TNF-�, than with other monoclonalantibody inhibitors.58

Table 7. Biologics Screening and Monitoring7,59

Biological Screen LabFollow Labs Every 2

to 6 Months Vaccine/Frequency PPD/Frequency

Etanercept CBC with differential CBC with differential Flu (standard for age) At baselineCMP CMP � AnnualANA (optional)

Adalimumab CBC with differential CBC with differential Flu (standard for age) At baselineCMP CMP � AnnualANA (optional)

Infliximab CBC with differential CBC with differential Flu (standard for age) At baselineCMP CMP � AnnualANA (optional)

Ustekinumab CBC with differential CBC with differential Flu (standard for age) At baselineCMP CMP � AnnualANA (optional)

CBC, complete blood count; CMP, complete metabolic panel; ANA, anti-nuclear antibody; PPD, purified protein derivative; Flu,inactivated influenza vaccine (avoid live vaccines).


spondylitis, Crohn’s disease, and psoriasis showed a3-fold higher rate of lymphoma compared with thegeneral US population.36,55,57 However, whenmeta-analyses of these randomized controlled trialswere considered, most of the patients who popu-lated the original trials were from cohorts withrheumatoid arthritis and Crohn’s disease, whichusually combined biological therapies with addi-tional immunosuppressive agents, therefore intro-ducing selection bias and confounding.61 In theabsence of TNF-� blocking therapy, patients withmoderate to severe rheumatoid arthritis, for exam-ple, have a 5- to 25-fold increased risk of develop-ing lymphoma.57 It is therefore unclear whetherthe increases in the rate of lymphoma observed inthese trials were related to TNF-� blocking ther-apy.Congestive Heart Failure/Cardiac Events. Becausesigns and symptoms of congestive heart failure canworsen while taking a biologic drug like a TNF-�inhibitor, physicians should monitor these patientscarefully and weigh the risk-to-benefit ratio.55 Ma-jor adverse cardiovascular events have been seenwith the use of interleukin-12/23 inhibitors,namely briakinumab, which was pulled from clini-cal trials.62,63 Ustekinumab data also show someevents, but further research is needed to clarify therole that these drugs may play in risk of majoradverse cardiovascular events and the mechanismby which they may occur.64 The rate of majoradverse cardiac events in patients taking usteki-numab was no greater than rates in both the gen-eral population and a population with psoriasis.7

Ustekinumab can cause reversible posterior leuko-encephalopathy syndrome, which presents as a per-sistent headache, seizures, sudden vision changes,and mental and mood changes,7 so establishing a neu-rological history and physical examination at baseline isimportant.

Reactivation of Varicella ZosterWhile the risk of potential reactivation of VZV isvery low when a patient is taking a biologicdrug,65,66 the risk increases when this patient is alsotaking oral prednisone for a comorbidity. Reacti-vation of VZV can lead to a potentially seriousneurological complication,67,68 and VZV vascu-lopathies in immunocompromised patients havebeen described in the literature.69 In these cases thepatient should be closely monitored for and edu-

cated about any signs or symptoms of stroke ortransient ischemic attack and administration ofVZV intravenous immunoglobulin should be con-sidered.

Basic Pharmacology of BiologicalsThe half-life of etanercept is 4 days, that of adali-mumab is 10 to 20 days, infliximab is 8 to 9.5 days,and ustekinumab is 14.9 to 45.6 days5; the timerequired for any of these drugs to be removed fromthe body once they are discontinued is approxi-mately 4 to 5 half-lives.70 Once a patient beginstaking a biologic drug, its important to closelyfollow them for drug-related adverse events. Rea-sons to stop a biologic drug are serious infection;severe persistent neurological symptoms such asheadache, eye pain, loss of vision in one eye, ornumbness; Guillain-Barre syndrome; lymph nodeswelling; unintended weight loss; malaise; easybruising; bleeding; pallor; or serious allergic reac-tion such as anaphylaxis or angioedema.36,55

Indications and DosingBecause of the significant cost of biologics, moretraditional medications should be tried first, if possi-ble, and biologics used only when those fail or there isa contraindication to oral systemic therapy. 71

Acitretin (SORT Criteria Recommendation A, Levelof Evidence 1)This drug should be completely avoided in womenof childbearing age because it is teratogenic andcategory X. Although acitretin may take 2 monthsto be eliminated from the body, when alcohol isconsumed, eretinate, its metabolite, can have a half-life of up to 168 days.72 It is recommended thatwomen abstain from consuming alcohol in anyform while taking the drug and for at least 2months after it is discontinued because the amountof metabolite is directly proportional to the amountof alcohol ingested.72 In fact, the teratogenic effectscan occur for up to 2 to 3 years after acitretindiscontinued in a patient who has consumed alco-hol.33,72 Because of this, it is advised that if pre-scribing this for women of childbearing age, theymust (1) have 2 negative urine or serum pregnancytests before receiving their first dose of acitretin; (2)have monthly pregnancy tests before receivingtheir acitretin prescriptions; (3) simultaneously use2 effective forms of birth control for at least 1month before starting the drug, during the therapy,


and for at least 3 years after discontinuing thetherapy; and (4) receive counseling about the risk ofbirth control failure and risk of birth defects andabstain from every form of alcohol while taking thedrug and for at least 2 months after the drug hasbeen discontinued.72

MonitoringA careful history and physical examination is im-portant to identify those at risk for or with a familyhistory of hyperlipidemia; a medicine reconcilia-tion is useful to note potential drug interactions.Monitoring parameters include complete meta-bolic and lipid panels at baseline, complete bloodcount with differential, and urinalysis.73 Lipids canbe checked every 1 to 2 weeks once treatment isstarted until they stabilize, which is usually in 4 to8 weeks, especially in patients with a personal orfamily history of hyperlipidemia.73 In those withouta significant history of or baseline hyperlipidemia,checking the lipid panel each month for 3 to 6months is recommended,73 especially to monitorfor acute pancreatitis, which is rare.73 Triglyceridelevels �600 mg/dL or cholesterol levels �300 mg/dLwarrant a discontinuation of acitretin and close mon-itoring of lipids until they return to baseline.73 Some-times, a fenofibrate is recommended for hypertriglyc-eridemia. Mild elevations in transaminases are rarelyseen 2 to 8 weeks after the start of acitretin, but theseare transient and just require monitoring.73 Checkingthe following laboratory values monthly for the first 3to 6 months then every 3 months in cases of chronicacitretin therapy is recommended: complete bloodcount with differential, lipid and complete metabolicpanels, and urinalysis. Common adverse reactions arexerostomia (dry mouth), cheilitis, alopecia, xerosis,and sunburn/sensitivity (especially if combined withphototherapy). Because elevated intracerebral pres-sure can also be an adverse event with acitretin,concomitant medications that have this adversereaction (eg, tetracyclines) are contraindicated.Finally, because acitretin is a vitamin A deriva-tive, any vitamin A supplementation should beavoided. Skeletal radiograph monitoring is notrequired.18

Methotrexate (SORT Criteria Recommendation A,Level of Evidence 1)After a full history and physical examination, rec-onciling additional medications is important be-cause of potential interactions with various drugs,

including all salicylates, nonsteroidal anti-inflam-matory drugs, trimethoprim/sulfamethoxazole, sul-fonamides, and tetracyclines, to name a few.50 Al-though it has oral, intramuscular, and intravenousroutes of administration, oral administration ismost common in the primary care setting. Metho-trexate (MTX) should not be given to anyone plan-ning to consume alcohol or women who are preg-nant or lactating. Risks versus benefits should bediscussed because of possible adverse effects; con-tinuous monitoring is required with this drug.About 80% of patients with psoriasis who aretreated with MTX respond usually within the first4 weeks.50 In addition, for those couples planningon having a family, it is advised that men takingMTX should be off the drug for 3 months andwomen should discontinue for 1 menstrual cycleand have a negative pregnancy test at each visit.49,50

MonitoringBefore starting a patient on MTX, a completeblood count with differential is required at baseline.This helps establish a baseline to follow for anypossible MTX-induced pancytopenia.50 A com-plete metabolic panel will examine for poor renalfunction, low albumin, and liver function at base-line, the first 2 of which can be potential sources ofpancytopenia because of increased levels of the freedrug.50 In patients with renal disease, the dose ofMTX can be adjusted according to the patient’screatinine clearance (as calculated using the Cock-croft-Gault formula49). Testing for human immu-nodeficiency virus, tuberculosis, and hepatitis B andC is important before starting MTX49 because it isan immunosuppressive drug. Not only can MTXinduce pancytopenia and hepatotoxcity, it can alsocause pulmonary fibrosis.49 If pulmonary symp-toms develop, a chest radiograph is warranted.49

Once a patient is taking MTX, it is important tomonitor for leukocytopenia or thrombocytopeniawith a complete blood count with differential 7 to14 days after starting or increasing the dose, every2 to 4 weeks for the first few months, then every 1to 3 months until stable.49 Leukocytopenia orthrombocytopenia are most likely to occur 7 to 10days after initiating MTX and clinically seriouscases can usually be corrected by 20 mg folinic acid(intravenous).49 Patients who are at highest risk ofMTX-induced pancytopenia, and therefore requireclose monitoring, are those who have renal insuf-ficiency, the elderly, those at risk for drug interac-


tions or taking multiple medications, those withhypoalbuminemia, or those who are not taking fo-late.49 A basic metabolic panel for renal function isrequired every 2 to 3 months for patients takingMTX; for patients with impaired renal function,glomerular filtration rate needs to be calculated andmonitored.49

The newest guidelines divide those patients whoare at low risk of developing hepatic fibrosis fromthose who are at highest risk. Patients are consid-ered to have hepatic fibrosis risk factors if they havediabetes mellitus type 2, are obese, consume excessalcohol, have hepatitis B or hepatitis C virus,and/or are exposed to hepatotoxic drugs.33 In thesepatients pretreatment biopsies may be warrantedand may be repeated after the patient has reached a1.0-g total cumulative dose.41 Its important to ob-tain the blood sample at least 5 days after the lastdose of MTX because the drug can erroneouslyelevate the results of liver function tests.49 Liverfunction tests showing minor elevations (less thantwice the upper limit of normal) can be repeated in2 to 4 weeks.49 Any abnormality (�3-fold the upperlimit of normal) in liver function testing necessi-tates a temporary reduction of MTX and repeat oftests within 2 to 4 weeks.49 If there are persistentelevations in serum aspartate aminotranferase andhypoalbuminemia for 12 months, a liver biopsyshould be considered before the patient reaches the1.5- to 2.0-g cumulative dose mark.41,49 WhetherMTX treatment should be initiated in high-riskpatients or those with any of the risk factors forhepatic fibrosis should be decided on a case-by-casebasis.49 If MTX is considered in these patients, abaseline liver biopsy is advisable; however, becausesome of these patients will discontinue MTX after2 to 6 months because of adverse events or lack ofefficacy, delaying a liver biopsy may also be advis-able.49 Low-risk patients require a liver biopsy ev-ery time they reach the 1.5- to 2.0-g total cumula-tive dose.41 Recommendations to continue ordiscontinue MTX based on liver biopsy are basedon the results of Roenigk et al.74 Whereas liverbiopsy remains the gold standard, it is fraught withrisk; a liver ultrasound (transient elastography) of-fers the ability to determine whether the liver isfibrosed, but studies can be limited, especially if thepatient is overweight, has increased abdominalgirth, or has a diagnosis of nonalcoholic steato-hepatitis.75

Cyclosporine (SORT Criteria Recommendation A,Level of Evidence 2)CsA is not contraindicated during pregnancy orlactation because it is a category C drug; however,it is contraindicated in patients with severe renalfunction, uncontrolled hypertension, and persistentmalignancy.53 During a complete history the pa-tient should be asked about anything that wouldincrease their risk of nephrotoxcity, such as obesity,diabetes mellitus, advanced age, and concomitantuse of nephrotoxic drugs.52 Exercise caution whendealing with patients taking multiple drugs becauseCsA has numerous drug-drug interactions due toits metabolism by the cytochrome p450 34A systemor when administering with foods like grapefruitjuice.33,76 During the complete physical examina-tion at baseline and at each monthly visit, patientsshould be evaluated for skin neoplasms or infec-tions because CsA increases the risk for developingsquamous and basal cell carcinomas.52 In addition,at baseline, all patients initiating CsA should un-dergo routine age-appropriate cancer screening.52

Testing for tuberculosis and hepatitis C at baselineis advisable.52 Because CsA is immunosuppressive,vaccines may be helpful, and booster vaccinationmay be necessary; however, live vaccines are con-traindicated with use of CsA.52

MonitoringBefore starting a patient on CsA, 2 confirmed nor-mal values for serum creatinine and blood pressureshould be documented in addition to completemetabolic panels, including liver function testing,bilirubin, potassium, blood urea nitrogen, creati-nine, complete blood counts, serum magnesium(which may decease while taking CsA), uric acid(which is relevant for those at risk for gout), andfasting serum lipids.52 Despite the recommenda-tions on the package insert, the current consensusnow requires monthly monitoring of renal function(creatinine clearance), blood pressure, physical ex-aminations, adverse events, and a basic metabolicpanel, including creatinine, blood urea nitrogen,potassium, complete blood count, and magne-sium.52 It is recommended that the Modification ofDiet in Renal Disease formula rather than theCockcroft-Gault equation be used for overweightpatients and those �50 years old.18 After checkingfasting serum lipids at the initiation of therapy,these levels can be tested at least every 6 months forevidence of hypercholesterolemia or hypertriglyc-


eridemia.52 Because of the monthly monitoring orlaboratory tests and examinations, obtaining a CsAlevel is generally not necessary.52

Treating patients for more than 1 to 2 yearswithout nephrology consultation is not recom-mended because of CsA-associated risk of nephro-toxicity.17,52 Patients taking long-term therapy arealso at risk of gingival hyperplasia, so yearly dentalexaminations are advised.52 The current recom-mendations for managing nephrotoxicity are re-ducing the dose of CsA by 25% to 50% (equivalentto 0.5 to 1.0 mg/kg/day) if serum creatinine levelsincrease more than 25% to 30% above baseline on2 occasions (repeated measurements separated by 2weeks).52 If serum creatinine fails to return to 10%of the patient’s baseline after checking the levelsevery other week for 1 month, the dose of CsAshould be reduced even further by 25% to 50%.52

Discontinuation of CsA should be considered ifserum creatinine remains �10% above the pa-tient’s baseline.52

For patients with no pre-existing hypertensionbut who developed hypertension while taking CsAas measured on 2 separate occasions, the PCP caneither reduce the dose of CsA by 25% to 50% ortreat the hypertension with a calcium channelblocker.52 For patients with existing hypertension,it is important to closely monitor blood pressure,serum creatinine, compliance, medications, diet,lifestyle, and drug interactions. For example, pa-tients taking angiotensin-converting enzyme inhib-itors will need to discontinue and replace them witheither calcium channel blockers or �-blockers.52

Dihydropyridine calcium channel blockers (eg, is-radipine and amplodipine) are more effective inreducing blood pressure and they can induce renalarteriolar vasodilation to contrast the vasoconstric-tive effects of CsA.77 Verapamil, diltiazem, andnicardipine can increase the levels of CsA in theblood; nifedipine can cause gingival hyperplasiaand should be avoided.77 Because of their abilityto spare potassium and potentiate hyperkalemiawith CsA, angiotensin-converting enzyme inhib-itors and potassium-sparing diuretics should beavoided.52 �-Blockers can be used.

ConclusionsPsoriasis vulgaris is a chronic and sometimes dis-figuring and disabling disease. With the growingpopulation, the decrease in health professionals,

and the large number of patients to be seen, it isimportant that PCPs are equipped with the toolsnecessary to understand, manage, and effectivelytreat psoriasis in a short amount of time. Dealingwith psoriasis as a complex systemic disease benefitsboth the provider and the patient. In general, top-ical therapies can be used for mild psoriasis. Formoderate to severe psoriasis, a combination of top-ical and light or topical and systemic (oral or bio-logicals) can be used. In these cases, the decision ofwhether to start oral versus biological therapy maybe personal and possibly guided by the patient’sfinances if the drug is not covered by a patient’sinsurance. Payment assistance programs such as thoseprovided by the manufacturer for patients taking Enbrel(http://www.enbrel.com/pay-for-ENBREL.jspx) andHumira (https://www.pparx.org/supporters/ViewProgram.php?program_id�526) are available. Earlyintervention and a multidisciplinary approach, man-aging all aspects of the patient’s care and comorbidi-ties, can be the focus of the PCP dealing with thischallenging disease.

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