Overview

Psoriasis is a common, chronic, relapsing, inflammatory skin disorder with a strong genetic basis. The plaque type of psoriasis is the most common, although several other distinctive clinical variants of psoriasis are recognized (eg, Guttate Psoriasis; Psoriasis, Nails; Psoriasis, Pustular; Psoriatric Arthritis). Plaque psoriasis is most typically characterized by circular-to-oval red plaques distributed over extensor body surfaces and the scalp. The plaques usually exhibit scaling as a result of epidermal hyperproliferation and dermal inflammation. The extent and duration of plaque psoriasis is highly variable from patient to patient. Acute flares or relapses of plaque psoriasis may also evolve into more severe disease, such as pustular or erythrodermic psoriasis. Up to 10-20% of patients with plaque psoriasis also experience psoriatic arthritis. A population-based study by Wilson et al that spanned more than 30 years reported that less than 10% of psoriasis patients develop clinically recognized psoriatic arthritis. The clinical features that were associated with an increased chance of leading to psoriatic arthritis were reported as being scalp lesions, nail dystrophy, and intergluteal or perianal psoriasis.[1] For more information, see Psoriasis.

Pathophysiology
The pathophysiology of psoriasis must be understood in terms of the prominent pathologies occurring in both major components of the skinthe epidermis and the dermis. Psoriasis is fundamentally an inflammatory skin condition with reactive abnormal epidermal differentiation and hyperproliferation. Current research suggests that the inflammatory mechanisms are immune based and most likely initiated and maintained primarily by T cells in the dermis.[2] In this model, antigen-presenting cells in the skin, such as Langerhans cells, are believed to migrate from the skin to regional lymph nodes, where they interact with T cells. Presentation of an as yet unidentified antigen to the T cells, as well as a number of co-stimulatory signals, triggers an immune response, leading to T-cell activation and the release of cytokines. Co-stimulatory signals are initiated via the interaction of adhesion molecules on the antigenpresenting cells, such as lymphocyte functionassociated antigen (LFA)3 and intercellular adhesion molecule-1, with their respective receptors CD2 and LFA-1 on T cells. These T cells are released into the circulation and traffic back into the skin. Reactivation of T cells in the dermis and epidermis and the local effects of cytokines such as tumor necrosis factor lead to the inflammation, cell-mediated immune responses, and epidermal hyperproliferation observed in persons with psoriasis. An interleukin (IL)-12related cytokine, IL-23, is involved in the establishment of chronic inflammation and in the development of a T helper (Th)cell subset producing IL-17. These cells, which are designated Th17, are distinct from Th1 and Th2 populations. Th17 cells are now recognized as a third T-effector cell subset, and the IL-23/IL-17 pathway has been

implicated in the induction and progression of a number of inflammatory diseases, including psoriasis.[3]

Environmental factors
Infection and a number of physical agents (eg, HIV infection, alcoholism, smoking, UV light) all can affect the course, duration, and clinical appearance of plaque psoriasis. See Etiology of Plaque Psoriasis, below, for more details on the role of environmental factors.

Etiology
Genetic factors
HLA-B13, -B17, and -Cw6 are all associated with plaque psoriasis. Multifactorial inheritance mechanisms and etiologies without any genetic component have not yet been excluded, although many families appear to exhibit autosomal dominant patterns of inheritance with decreased penetrance. Studies of twin siblings have shown concordant disease in 73% of monozygotic twins compared with 20% in dizygotic twins. Several putative genetic susceptibility loci have also been identified, including psoriasis susceptibility 1 (PSOR1) on chromosome 6, which is associated with up to 50% of cases. Six other psoriasis susceptibility loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7) have been discovered, as well as the transcription factor RUNX1. While this certainly points to genetic mechanisms, the absence of 100% concordance among monozygotes suggests that environmental factors must play a role in the pathophysiology of this disease.

Trauma
All types of trauma have been associated with the development of plaque psoriasis (eg, physical, chemical, electrical, surgical, infective, and inflammatory injury). Even excessive scratching can aggravate or precipitate localized psoriasis. The development of psoriatic plaques at a site of injury is known as the Koebner reaction.

Sunlight
Most patients consider sunlight to be beneficial for their psoriasis; they report a decrease in illness severity during the summer months or periods of increased sun exposure. However, a small minority of patients find that their symptoms are aggravated by strong sunlight, and these individuals actually experience a worsening of their disease in the summer. A severe sunburn can lead to an exacerbation of plaque psoriasis via the Koebner reaction.

Infection
Pharyngeal streptococcal infections have been shown to produce a clinically distinctive disease flare known as guttate psoriasis. Some evidence suggests that subclinical streptococcal colonization or overgrowth could be responsible for refractory plaque psoriasis.

HIV infection

An increase in psoriasis activity has been observed in patients who are infected, or become infected, with HIV. The extent and severity of skin disease initially appears to parallel the disease stage. Psoriasis often becomes less active in advanced HIV infection.

Drugs
A number of medications have been shown to cause an exacerbation of psoriasis. Lithium and withdrawal from systemic corticosteroids are well known to cause flares of disease. Betablockers, antimalarials, and nonsteroidal anti-inflammatory drugs (NSAIDs) have also been implicated.

Psychogenic/emotional factors
Many patients report an increase in psoriasis severity with psychological stress. A clear cause-and-effect relationship between disease exacerbation and stress unfortunately has not been proven. Patients may show a decreased capacity to cope with their treatment regimen with higher levels of stress. Pruritus in the setting of increased anxiety or depression may promote scratching and a Koebner reaction.

Smoking
An increased risk of chronic plaque psoriasis exists in persons who smoke cigarettes.

Alcohol consumption
Alcohol consumption is considered a risk factor for psoriasis, particularly in young to middleaged men.

Endocrinologic factors
Psoriasis severity has been noted to fluctuate with hormonal changes. Disease incidence peaks at puberty and during menopause. During pregnancy, symptoms are more likely to improve than worsen, if any changes occur at all. In contrast, the disease is more likely to flare in the postpartum period, again if any changes occur at all.

Epidemiology
Plaque psoriasis occurs worldwide, although its prevalence varies with race, geography, and environmental factors (eg, sun exposure). In the United States, 1-2% of the population has plaque psoriasis. Family history has been shown to predict disease occurrence. When both parents are affected by psoriasis, the rate in siblings of probands is as high as 50%. When one parent is affected, the rate is 16.4%. When neither parent has psoriasis, only 7.8% of siblings of probands are affected. Of patients with psoriasis, 36-71% have one relative who is also affected by psoriasis. For siblings of patients whose psoriasis appeared before age 15 years, a 3-fold higher risk exists

of developing disease compared with siblings of patients who first presented after age 30 years. Psoriasis affects adult males and females equally. Among children and adolescents, plaque psoriasis has been found to affect females more than males, but this observation may be due to the earlier age of onset in females. Plaque psoriasis first appears during 2 peak age ranges. The first peak occurs in persons aged 16-22 years, and the second occurs in persons aged 57-60 years. Females develop plaque psoriasis earlier than males, and patients with a positive family history for psoriasis also tend to have an earlier age of onset.

Mortality and morbidity

Disease-related mortality is exceedingly rare in psoriasis. Even then, mortality is related primarily to therapy: systemic corticosteroid therapy may provoke pustular flares of disease, which can be fatal; methotrexate therapy may result in hepatic fibrosis; and phototherapy (eg, psoralen plus UVA [PUVA]) may induce skin cancers, with subsequent metastasis. Morbidity is a much greater problem in patients with psoriasis; it includes pruritus, dry and peeling skin, fissuring, self-consciousness and embarrassment about appearance, inconvenience, and the adverse effects and high cost of antipsoriatic treatment regimens. By far, reduced quality of life is the most significant morbidity. Studies have demonstrated that patients with psoriasis have deficiencies in quality of life similar to those for persons with congestive heart failure. An association between psoriasis, obesity, and cardiovascular comorbidity was been recognized amongst patients with plaque psoriasis. This appears to be strongest in younger patients with severe disease. The association seems to be related to the metabolic syndrome, a state of chronic systemic inflammation characterized by at least 3 of the following:

Abdominal obesity Impaired glucose regulation Hypertriglyceridemia Reduced high-density lipoprotein levels Hypertension

Psoriasis and obesity are now believed to share similar mediators (eg, cytokines tumor necrosis factor [TNF]alpha and IL-6) that drive the inflammatory process in these conditions. This finding, as it becomes further elucidated, may have future implications on health screening and treatment of patients with psoriasis.[4]

Racial disparity in psoriasis

Psoriasis can affect persons of any race; however, epidemiologic studies have shown a higher prevalence in western European and Scandinavian populations. In these groups, 1.5-3% of the population is affected by the disease.

The highest documented disease prevalence is in Arctic Kasach'ye, with 12% of the population affected, followed by Norway, where 4.8% of the population has psoriasis. Lower prevalence rates for psoriasis have been reported among Japanese and Inuit populations. Psoriasis is thought to be rare in West Africans and African Americans and is nearly absent in North American Indians. Psoriasis was undetected in the Samoan population and in a study that examined 26,000 South American Indians.

Clinical Presentation
Patient history
The typical history given by a patient with plaque psoriasis is relatively straightforward: patients report prominent itchy, red areas with increased skin scaling and peeling. Patients are particularly aware of lesions on the scalp and extensor surfaces. Patients typically are selfconscious about their lesions and commonly report using clothing to cover affected sites and avoiding potentially embarrassing social activities. Patients commonly recognize that new lesions appear at sites of injury or trauma to the skin. This isomorphic phenomenon (Koebner reaction) typically occurs 7-14 days after the skin has been injured and has been found in 38-76% of patients with plaque psoriasis. In some patients, so-called reverse-Koebner reactions have also been noted in which preexisting psoriatic plaques actually clear after injury or trauma to the skin. Patients may report that their disease worsens in the winter and improves in the summer. Significant joint pain, stiffness, and deformity are reported in the 10-20% of patients with psoriasis who develop psoriatic arthritis.

Physical examination
Several cardinal features of plaque psoriasis can be readily observed during the physical examination.

Plaques
Psoriasis manifests as elevated lesions that vary in size from one to several centimeters (see image below). The thickened epidermis, expanded dermal vascular compartment, and infiltrate of neutrophils and lymphocytes account for the psoriatic lesions being raised and easily palpable. The number of lesions may range from few to many at any given time.

Plaque psoriasis. Courtesy of University of British Columbia, Department of Dermatology and Skin Science.

The plaques are irregular to oval and are most often located on the scalp, trunk, and limbs, with a predilection for extensor surfaces such as the elbows and knees. Smaller plaques may coalesce into larger lesions, especially on the legs and sacral regions (see image below). Fissuring within plaques can occur when lesions are present over joint lines or on the palms and soles.

Plaque psoriasis. Courtesy of University of British Columbia, Department of Dermatology and Skin Science.

Well-circumscribed margins
Psoriatic plaques are well defined and have sharply demarcated boundaries. Psoriatic plaques occasionally appear to be immediately encircled by a paler peripheral zone referred to as the halo or ring of Woronoff.

Red color
The color of psoriatic lesions is a very distinctive rich, full, red color. Lesions on the legs sometimes carry a blue or violaceous tint.

Scale
Psoriatic plaques typically have a dry, thin, silvery-white or micaceous scale; however, the amount and thickness of this scale is quite variable. Removing the scale reveals a smooth, red, glossy membrane with tiny punctate bleeding points. These points represent bleeding from enlarged dermal capillaries after removal of the overlying suprapapillary epithelium. This phenomenon is known as the Auspitz sign.

Symmetry
Psoriatic plaques tend to be symmetrically distributed over the body. Lesions typically have a high degree of uniformity with few morphologic differences between the 2 sides.

Pruritus
Pruritus, one of the main symptoms of plaque psoriasis, is quite variable in intensity but should not be ignored. Emotional instability (eg, high levels of anxiety, depression) that might be induced by the disease often manifests as an increased tendency to scratch.

Nail psoriasis
Nail changes are commonly observed in patients with plaque psoriasis. Nails may exhibit pitting, onycholysis, subungual hyperkeratosis, or the oil-drop sign. A proper assessment of any patient suspected of having psoriasis should include careful examination of the nails.

Psoriasis in children
Plaque psoriasis manifests slightly differently in children. Plaques are not as thick, and the lesions are less scaly. Psoriasis may often appear in the diaper region in infancy and in flexural areas in children. The disease more commonly affects the face in children compared with adults.

Inverse psoriasis
This is a variant of psoriasis that spares the typical extensor surfaces and affects intertriginous (ie, axillae, inguinal folds, inframammary creases) areas with minimal scale.

Psoriatic arthritis
Approximately 10-20% of all cases of plaque psoriasis are associated with psoriatic arthritis. Signs of psoriatic arthritis include the following:

Red, warm, tender, and inflamed joints Joint deformity Dactylitis Sausage digits

Obesity
Patients with obesity and psoriasis may have an increased risk of cardiovascular disease. This association appears to be strongest in younger patients with severe disease and may be related to the metabolic syndrome.[4]

Alcoholism
Alcoholism can be considered a complication of psoriasis. Male patients with severe disease are particularly at risk for this type of substance abuse.

Differential Diagnosis
The differential diagnosis of plaque psoriasis includes the following:

Bowen Disease Drug Eruptions Erythema Annulare Centrifugum Lichen Planus Lichen Simplex Chronicus Lupus Erythematosus, Discoid

Nummular Dermatitis Parapsoriasis Pityriasis Rosea Seborrheic Dermatitis

Laboratory Studies
The diagnosis of psoriasis is almost always made on the basis of clinical findings. Laboratory investigations are rarely indicated. In severe cases, patients may have mild hyperuricemia and low folate levels, presumably because of enhanced epidermopoiesis.

Skin Biopsy
Skin biopsies can confirm the diagnosis of plaque psoriasis; however, this is usually reserved for the evaluation of atypical cases or for excluding other conditions in cases of diagnostic uncertainty. See Histologic Findings, below, for more details on plaque histology.

Histologic Findings of the Epidermis

Mitotic activity of basal keratinocytes is increased almost 50-fold, with keratinocytes migrating from the basal to the cornified layers in only 3-5 days rather than the normal 28-30 days. With hyperproliferation of skin cells, the epidermis becomes thickened or acanthotic in appearance and the rete ridges increase in size. Abnormal keratinocyte differentiation is noted throughout the psoriatic plaques, as manifested by the loss of the granular layer. The stratum corneum is also thickened, and the retention of cell nuclei in this layer is referred to as parakeratosis. Neutrophils and lymphocytes can be observed migrating upwards from the dermis into the acanthotic epidermis. Neutrophils may form localized collections known as Munro microabscesses. The presence of alternating collections of neutrophils sandwiched between layers of parakeratotic stratum corneum is virtually pathognomonic for psoriasis. (See image below.)

Plaque psoriasis. Photomicrograph of psoriasis. (1) Hyperkeratosis and parakeratosis, (2) neutrophils in the epidermis, (3) thinning of the epidermis overlying the dermal papillae, (4) vessels close to the epidermis, and (5) elongated rete ridges. Courtesy of Richard Crawford, MD, University of British Columbia, Department of Dermatology and Skin Science.

Histologic Findings of the Dermis

Signs of inflammation can be observed throughout the dermis in persons with plaque psoriasis. Marked hypervascularity and an increase in the size of the dermal papillae occur. An activated CD3+ lymphocytic infiltrate is noted around blood vessels, with T cells expressing cutaneous lymphocyteassociated antigen, co-stimulatory molecules such as CD2, and lymphocyte function-associated antigen1 (LFA-1) adhesion molecules. An aggregation of neutrophils in the dermis occurs that extends up into the epidermis.

Overview of Treatment
Plaque psoriasis is a chronic skin condition. Any approach to the treatment of this disease must be considered for the long term. Treatment regimens must be individualized according to age, sex, occupation, personal motivation, other health conditions, and available resources. Disease severity is defined not only by the number and extent of plaques present but also by the patient's perception and acceptance of the disease. Treatment, therefore, must be designed with the patient's specific expectations in mind rather than the extent of the body surface area involved.[5] Many treatments exist for psoriasis; however, the construction of an effective therapeutic regimen is not necessarily complicated. Three basic treatment modalities are available for the overall management of psoriasis: topical agents; phototherapy; and systemic agents, including biologic therapies. All of these treatments may be used alone or in combination.

American Academy of Dermatology Guidelines

The American Academy of Dermatology has published guidelines of care for the management of psoriasis and psoriatic arthritis. See the following sections:

Section 1. overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics[6] Section 2. psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics[7]

Topical Therapy
Outpatient topical therapy is the first-line treatment of plaque psoriasis. A number of topical treatments are available (eg, corticosteroids, coal tar, anthralin, calcipotriene, tazarotene). No single topical agent is ideal for plaque psoriasis, and many are often used concurrently in a combined approach. With the different adverse effect profiles for the various agents, using a rotational therapeutic approach in which different topical agents are used sequentially over time in the same patient is common. In general, the effects of topical therapy should become evident within the first 2-3 weeks of use. Clearing of scale is usually observed first, followed by flattening of the treated plaques. Resolution of erythema may take 6-8 weeks.

Auxiliary agents such as keratolytics can often be added to these preparations. However, some auxiliary agents are incompatible with the active ingredients of these preparations. For example, salicylic acid inactivates calcipotriene. On the other hand, agents such as anthralin require the auxiliary agent salicylic acid for chemical stability.

Phototherapy
Initiate phototherapy only in the presence of extensive and widespread disease (generally practically defined as more lesions than can be easily counted). Resistance to topical treatment is another indication for phototherapy. The 2 main forms of phototherapy are ultraviolet B (UVB) irradiation psoralen plus ultraviolet A irradiation (PUVA). Proper facilities are required for both UVB irradiation and PUVA photochemotherapy. UVB irradiation uses light with wavelengths of 290-320 nm (in comparison, the visible light range is 400-700 nm). Narrow-band UVB phototherapy uses a fluorescent bulb with a narrow emission spectrum that peaks at 311 nm. This selective and relatively longer wavelength is more effective than broadband UVB for the treatment of plaque-type psoriasis, and poses less risk of burning.[8] Excimer laser UVB therapy can deliver high-dose light to limited plaques. UVB therapy is usually combined with one or more topical treatments. The Goeckerman regimen uses coal tar followed by UVB exposure and has been shown to induce disease remission in more than 80% of patients. The Ingram method comprises anthralin application following a tar bath and UVB treatment. At present, UVB is more commonly combined with topical corticosteroids, calcipotriene, tazarotene, or simply bland emollients. UVB phototherapy is extremely effective for treating moderate-to-severe plaque psoriasis. The major drawback of this therapy is the time commitment required for treatments and the accessibility of the UVB equipment. Patients may dislike the unpleasant odor when coal tar is added. Home ultraviolet therapy can overcome some of the logistical problems associated with phototherapy. Because of the expense of the home units, it is most suitable for patients who require long-term maintenance therapy. PUVA photochemotherapy, also known as PUVA, uses the photosensitizing drug methoxsalen (8-methoxypsoralens) in combination with UVA irradiation to treat patients with more extensive disease. UVA irradiation uses light with wavelengths of 320-400 nm. PUVA interferes with DNA synthesis, decreases cellular proliferation, and induces apoptosis of cutaneous lymphocytes, leading to a localized immunosuppression. More than 85% of patients report relief of disease symptoms with 20-30 treatments. Therapy is usually administered 2-3 times per week in an outpatient setting, with maintenance treatments every 2-4 weeks until remission. Adverse effects of PUVA therapy include nausea, pruritus, and a burning sensation. Longterm complications include increased risks of photo damage to the skin and (more

importantly) skin cancer. PUVA has been combined with oral retinoid derivatives to decrease the cumulative dose of UVA radiation to the skin.

Systemic Agents
Initiate systemic treatment only after both topical treatments and phototherapy have proved unsuccessful. Consider systemic therapy for patients with very active psoriatic arthritis. Patients who have disease that is physically, psychologically, socially, or economically disabling are also considered candidates for systemic treatment. All patients must be informed of the risks and adverse effects of systemic therapy before treatment is initiated.[9, 10,
11]

Biologic Therapies
These relatively new systemic therapies provide selective, immunologically directed intervention at key steps in the pathogenesis of the disease.[12] These steps include the following:

Inhibiting the initial cytokine release and Langerhans cell migration Targeting activated T cells, preventing further T-cell activation, and eliminating pathologic T cells Blocking the interactions that lead to T-cell activation or migration into tissue Altering the balance of T-cell types Inhibiting proinflammatory cytokines such as tumor necrosis factor (TNF),[13] IL-12, and IL-23[14]

As with the systemic agents, biologic therapies are typically reserved for more severe and recalcitrant cases.[15, 16, 17, 18, 19, 20, 21, 22, 23] Patients with active psoriatic arthritis in addition to their skin disease should also be considered. In a study completed by the Psoriatic Arthritis Study Group, beneficial effects were observed for patients with psoriasis and psoriatic arthritis on stable doses of methotrexate when one or more courses of intramuscular alefacept were added. Further benefit in psoriatic arthritis was apparent after a second course of alefacept, and no additional toxicity was observed.[24] Psoriasis of the palms and soles is more difficult to treat than psoriasis on other body sites. Adalimumab is effective, but only 31% of patients treated with adalimumab for hand or foot psoriasis in a placebo-controlled trial achieved clear or almost clear.[25]

Consultations
Consider consultation with a rheumatologist for patients who have evidence of psoriatic arthritis. Patients with cardiovascular comorbidities should be considered for referral to a cardiologist. Evidence-based guidelines have been published on the management of cardiovascular morbidities.[26]

Diet

Alcohol is considered a risk factor for psoriasis in young to middle-aged males. All patients with psoriasis should avoid or minimize alcohol use; patients with dependency states should be appropriately treated. Otherwise, specific dietary restrictions or supplements other than a well-balanced and adequate diet are unimportant in the management of plaque psoriasis.

Deterrence/Prevention
Avoiding specific exacerbating factors (see Etiology of Plaque Psoriasis for details) may help prevent or minimize flare-ups of psoriasis in some patients, although the cause of disease exacerbation in many patients often is unknown.

Complications of Treatment
Overly aggressive use of topical steroids could produce progression from plaque psoriasis to generalized pustular or erythrodermic forms. Topical steroids used with occlusion increase the risk of developing cutaneous atrophy. Potential adverse effects of systemic agents and phototherapy should be monitored on a regular basis and treated as soon as possible.

Patient Education
Patient education is one of the foundations for managing this chronic and typically relapsing disorder. Not only is psoriasis associated with morbidity, its treatment can also cause significant adverse effects (even death in rare instances). Patients should be familiar with these details in order to make proper and informed decisions about therapy. The National Psoriasis Foundation is an excellent organization that provides support to patients with psoriasis. For patient education information, see the Psoriasis Center, as well as What Is Psoriasis?, Plaque Psoriasis, Types of Psoriasis, Understanding Psoriasis Medications, and Nail Psoriasis.

Prognosis of Plaque Psoriasis

The course of plaque psoriasis is unpredictable. Predicting the duration of active disease, the time or the frequency of relapses, or the duration of a remission is impossible. The disease rarely is life threatening but often is intractable to treatment, with relapses occurring in most patients. Both early onset and a family history of disease are considered poor prognostic indicators. Some suggest that stress is also associated with an unfavorable prognosis. Environmental factors (particularly sunlight and warm weather) help alleviate the disease and are considered advantageous. Methotrexate, PUVA, cyclosporine, oral retinoids, and biologic therapies all have helped induce and maintain remission in severe cases of plaque psoriasis.

Dermatophytoses
Dermatophytes are a unique group of fungi that are capable of infecting nonviable keratinized cutaneous epithelium including stratum corneum, nails, and hair. Dermatophytic genera include Trichophyton, Microsporum, and Epidermophyton. The term dermatophytosis thus denotes a condition caused by dermatophytes. It can be further specified according to the tissue mainly involved: epidermomycosis (epidermal dermatophytosis), trichomycosis (dermatophytosis of hair and hair follicles), or onychomycosis (dermatophytosis of the nail apparatus). The term tinea should be reserved for dermatophytoses and is modified according to the anatomic site of infection, e.g., tinea pedis. "Tinea" versicolor is better called pityriasis versicolor in that it is caused by Pityrosporum yeast and not dermatophytes.

Causes of Dermatophytoses
Dermatophytes synthesize keratinases that digest keratin and sustain existence of fungi in keratinized structures. Cell-mediated immunity and antimicrobial activity of polymorphonuclear leukocytes restrict dermatophyte pathogenicity.

Host factors that facilitate dermatophyte infections: atopy, topical and systemic glucocorticoids, ichthyosis, collagen vascular disease Local factors favoring dermatophyte infection: sweating, occlusion, occupational exposure, geographic location, high humidity (tropical or semitropical climates)

The clinical presentation of dermatophytoses depends on several factors: site of infection, immunologic response of the host, species of fungus. Dermatophytes (e.g., T. rubrum) that initiate little inflammatory response are better able to establish chronic infection. Organisms such as M.canis cause an acute infection associated with a brisk inflammatory response and spontaneous resolution. In some individuals, infection can involve the dermis, as in kerion and Majocchi's granuloma.

Treatment
Topical antifungal preparations These preparations may be effective for treatment of dermatophytoses of skin but not for those of hair or nails. Preparation is applied bid to involved area optimally for 4 weeks including at least 1 week after lesions have cleared. Apply at least 3 cm beyond advancing margin of lesion. These topical agents are comparable. Differentiated by cost, base, vehicle, and antifungal activity.

Imidazoles Clotrimazole (Lotrimin, Mycelex), Miconazole (Micatin), Ketoconazole (Nizoral), Econazole (Spectazole), Oxiconizole (Oxistat), Sulconizole (Exelderm) Allylamines Naftifine (Naftin), Terbinafine (Lamisil)

Systemic antifungal agents For infections of keratinized skin: use if lesions are extensive or if infection has failed to respond to topical preparations. Usually required for treatment of tinea capitis and tinea

unguium. Also may be required for inflammatory tineas and hyperkeratotic moccasin-type tinea pedis.

Terbinafine 250-mg tablet. Allylamine. Rarely, nausea; dyspepsia, abdominal pain, loss of sense of taste, aplastic anemia. Most effective oral antidermophyte antifungal; low efficacy against other fungi. Azole/imidazoles Itraconazole and ketoconazole have potential clinically important interactions when administered with astemizole, calcium channel antagonists, cisapridecoumadin, cyclosporin A, oral hypoglycemic agents, phenytoin, protease inhibitors, tacrolimus, terfenadine, theophylline, trimetrexate, and rifampin. Griseofulvin Micronized: 250- or 500-mg tablets; 125 mg/teaspoon suspension. Ultramicronized: 165- or 330-mg tablets. Active only against dermatophytes; less effective than triazoles. Adverse effects include headache, nausea/vomiting, photosensitivity; lowers effect of crystalline warfarin sodium. T. rubrum and T.tonsurans infection may respond poorly. Should be taken with fatty meal to maximize absorption. In children, CBC and LFTs recommended if risk factors for hepatitis exist or treatment lasts longer than 3 months. Not used in Europe.

Diagnosis and Treatment of Lichen Planus

RICHARD P. USATINE, MD, and MICHELLE TINITIGAN, MD, University of Texas Health Science Center, San Antonio, Texas Am Fam Physician. 2011 Jul 1;84(1):53-60. Patient information: A handout on this topic is available at http://familydoctor.org/600.xml. Lichen planus is a chronic, inflammatory, autoimmune disease that affects the skin, oral mucosa, genital mucosa, scalp, and nails. Lichen planus lesions are described using the six P's (planar [flat-topped], purple, polygonal, pruritic, papules, plaques). Onset is usually acute, affecting the flexor surfaces of the wrists, forearms, and legs. The lesions are often covered by lacy, reticular, white lines known as Wickham striae. Classic cases of lichen planus may be diagnosed clinically, but a 4-mm punch biopsy is often helpful and is required for more atypical cases. High-potency topical corticosteroids are first-line therapy for all forms of lichen planus, including cutaneous, genital, and mucosal erosive lesions. In addition to clobetasol, topical tacrolimus appears to be an effective treatment for vulvovaginal lichen planus. Topical corticosteroids are also first-line therapy for mucosal erosive lichen planus. Systemic corticosteroids should be considered for severe, widespread lichen planus involving oral, cutaneous, or genital sites. Referral to a dermatologist for systemic therapy with acitretin (an expensive and toxic oral retinoid) or an oral immunosuppressant should be considered for patients with severe lichen planus that does not respond to topical treatment. Lichen planus may resolve spontaneously within one to two years, although recurrences are common. However, lichen planus on mucous membranes may be more persistent and resistant to treatment. Lichen planus is a chronic, inflammatory, autoimmune disease1 occurring in 0.1 to 4 percent of the general population, most often in perimenopausal women.2 Lichen planus can appear at any age, but most cases occur between 30 and 60 years of age.2

Pathophysiology
Although the exact etiology of lichen planus is unknown, an immune-mediated pathogenesis is recognized.1 A meta-analysis of primarily case-control studies conducted in multiple countries found a statistically significant association between hepatitis C virus (HCV) infection and lichen planus,3 although there is no known explanation for this association. Compared with the control group, patients with lichen planus had a greater prevalence of HCV exposure (odds ratio = 5.4; 95% confidence interval, 3.5 to 8.3), and patients with HCV infection had an increased prevalence of lichen planus (odds ratio = 2.5; 95% confidence interval, 2.0 to 3.1).3 It is appropriate to screen all patients with lichen planus for HCV infection.4 Patients should be asked about HCV risk factors, and liver enzyme and HCV antibody tests should be ordered.
SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation

Evidence rating

References

High-potency topical corticosteroids should be first-line treatments for all forms of lichen planus. Topical calcineurin inhibitors, such as tacrolimus (Protopic) and pimecrolimus (Elidel), should be used as second-line therapies to treat genital and oral lichen planus. Intralesional triamcinolone acetonide (Kenalog), 5 to 10 mg per mL injection, should be used to treat hypertrophic lichen planus. Three to six weeks of oral prednisone therapy should be used to treat severe, widespread lichen planus (tapered course, 30 to 60 mg per day starting dose).

B B

1416 15,17,21

B B

14 10,14

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

Clinical Presentation
Lichen planus lesions are described using the six P's (Table 1). Onset is usually acute, affecting the flexor surfaces of the wrists (Figure 15), forearms, and legs. These lesions are often covered by lacy, reticular, white lines known as Wickham striae (Figure 25). The lesions may appear in a linear configuration, following the lines of trauma (Koebner phenomenon; Figure 3). It is common to see post-inflammatory hyperpigmentation as the cutaneous lesions clear, especially in persons with darker skin. Although lichen planus often occurs only on cutaneous surfaces, it may also involve the oral mucosa, genital mucosa, scalp, or nails.6

Table 1. The Six P's to Describe Lichen Planus Lesions

Planar (flat-topped) Purple Polygonal Pruritic Papules Plaques

Figure 1. Lichen planus with papules and plaques on the wrist. Reprinted with permission from Kraft R, Usatine RP. Lichen planus. In: The Color Atlas of Family Medicine. Usatine RP, Smith MA, Chumley H, Mayeaux EJ Jr., Tysinger J, eds. New York, NY: McGraw-Hill; 2009:638.

Figure 2. Lichen planus on the feet. The reticular white scale of Wickham striae is visible on some of the plaques. Reprinted with permission from Kraft R, Usatine RP. Lichen planus. In: The Color Atlas of Family Medicine. Usatine RP, Smith MA, Chumley H, Mayeaux EJ Jr., Tysinger J, eds. New York, NY: McGraw-Hill; 2009:637.

Figure 3. Lichen planus on the wrist showing the Koebner phenomenon (arrow) with linear formations of papules. Copyright Richard P. Usatine, MD Cutaneous lichen planus may present in different forms. Linear lichen planus (Figure 3) manifests as closely aggregated linear lesions on the limbs that may develop the Koebner phenomenon. Annular lichen planus (Figure 4) accounts for approximately 10 percent of lichen planus cases.7 It commonly appears as arcuate groupings of individual papules that develop rings or a peripheral extension of clustered papules with central clearing. In addition to the usual sites of distribution, this form of lichen planus may occur on male genitalia and buccal mucosa.7 Atrophic lichen planus (Figure 5) is a rare form that is characterized by a few well-demarcated white, pink, or bluish papules, patches, or plaques with superficial atrophy. Hypertrophic lichen planus (lichen planus verrucosus; Figure 6) usually occurs on the extremities, especially the ankles, shins, and interphalangeal joints, and it tends to be the most pruritic form.7 It is often chronic with residual scarring and pigmentation when lesions clear. In vesiculobullous lichen planus (Figure 7), vesicles or bullae develop from preexisting lesions on the lower limbs, back, or buttocks, or in the mouth. Erosive/ulcerative lichen planus lesions develop within oral lesions or start as waxy semitranslucent plaques on the soles.8

Figure 4. Annular lichen planus on the breast. Copyright Richard P. Usatine, MD

Figure 5. Atrophic lichen planus on the forearm showing multiple colors within the atrophic lesions. Copyright Richard P. Usatine, MD

Figure 6. Hypertrophic lichen planus on the leg. Copyright Richard P. Usatine, MD

Figure 7. Bullous lichen planus on the buttocks. Copyright Richard P. Usatine, MD

Patients with oral lichen planus often have concomitant manifestations in other extraoral sites.1 A study showed that the vulva and vagina were also affected in approximately 25 percent of patients with oral lichen planus; involvement of the nails, scalp, esophagus, or eyes was less common.8 Oral lichen planus lesions are often asymptomatic. However, the condition is occasionally complicated by extensive painful erosions, leading to a considerable decrease in quality of life. Sensitivity to heat and a burning sensation may also occur. Intensive therapy is often required to reduce these complications.9 There are four forms of oral lichen planus: reticular, atrophic, bullous, and erosive.6 The reticular form is most common and manifests as bilateral, asymptomatic Wickham striae on the oral mucosa (Figure 8) or other parts of the mouth, such as the gingiva, tongue, palate, and lips (Figure 95). The atrophic form causes atrophic changes with erythema of the oral mucosa. The bullous form manifests as fluid-filled vesicles. The erosive form leads to ulcerated, painful, erythematous areas that may contract secondary infection, such as candidiasis. These ulcerated areas may have Wickham striae and occur in one or multiple sites of the mouth. Erosive lichen planus of the gums resembles desquamative gingivitis. Malignant transformation has been reported in men with oral erosive lichen planus lesions.10

Figure 8. Oral lichen planus with Wickham striae on buccal mucosa. Copyright Richard P. Usatine, MD

Figure 9. Oral lichen planus with erosions on the lips, tongue, and palate. Reprinted with permission from Kraft R, Usatine RP. Lichen planus. In: The Color Atlas of Family Medicine. Usatine RP, Smith MA, Chumley H, Mayeaux EJ Jr., Tysinger J, eds. New York, NY: McGraw-Hill; 2009:638. Lichen planus affecting the genitalia is more common in men. It typically presents on the glans penis and may have an annular pattern (Figure 105). Less commonly, linear, white striae similar to the lesions that typically appear on the vulva and vagina occur on the penis and scrotum. Reticular papules or severe erosions may appear on the vulva and become complicated by urethral stenosis. 11,12 Dyspareunia and pruritus are common with vulvar and vaginal lesions.11,12 Two reports show that more than 50 percent of women with oral lichen planus have undiagnosed vulvar lichen planus.11,12

Figure 10. Lichen planus on the penis showing a lacy, white, annular pattern. Reprinted with permission from Kraft R, Usatine RP. Lichen planus. In: The Color Atlas of Family Medicine. Usatine RP, Smith MA, Chumley H, Mayeaux EJ Jr., Tysinger J, eds. New York, NY: McGraw-Hill; 2009:639. Approximately 10 percent of patients with lichen planus present with scalp and nail variants. Scalp lesions (lichen planopilaris) are violaceous, scaly, pruritic papules that can progress to scarring alopecia if untreated13 (Figure 11). Nail involvement is characterized by irregular, longitudinal grooving and ridging of the nail plate; thinning of the nail plate; nail pterygium (i.e., cuticular overgrowth); shedding of the nail plate with atrophy of the nail bed; subungual keratosis; longitudinal erythronychia or melanonychia; and subungual hyperpigmentation.7

Figure 11. Lichen planopilaris causing hair loss with visible dark dots from follicular plugging. Copyright Richard P. Usatine, MD

Diagnosis
Lichen planus can be diagnosed clinically in classic cases, although biopsy is often helpful to confirm the diagnosis and is required for more atypical presentations. A 4-mm punch biopsy should be adequate on the skin or in the mouth. The histology shows a characteristic sawtooth pattern of epidermal hyperplasia; hyperparakeratosis with thickening of the granular cell layer; and vacuolar alteration of the basal layer of the epidermis, with an intense infiltration (mainly T cells) at the dermal-epidermal junction. A 4-mm punch biopsy of perilesional skin for direct immunofluorescence may be added to the workup when bullous

lesions, pemphigus, or bullous pemphigoid is present. Tables 2 and 3 present the differential diagnosis of cutaneous and oral lichen planus.
Table 2. Differential Diagnosis of Cutaneous Lichen Planus

Condition

Distinguishing features*

Treatment

Eczema

Excoriations and lichenification of Topical steroids and emollients skin, often on flexor surfaces Lichen One or more plaques with Potent topical steroids; help patient avoid simplex lichenification in an area that is scratching and picking at skin chronicus easily scratched Pityriasis rosea Herald patch preceding annular Reassurance (self-limited condition) plaques with collarette scale Prurigo Pruritic nodules, often on the Potent topical steroids, oral antipruritic nodularis extremities medications, help patient avoid scratching and picking at skin Psoriasis Plaques with thick scale on Potent topical steroids, topical vitamin D, extensor surfaces other treatments

*Diagnosis is based on history and clinical appearance; 4-mm punch biopsy should be performed when diagnosis is uncertain.
Table 3. Differential Diagnosis of Oral Lichen Planus

Condition

Distinguishing features

Diagnostic method

Treatment

Bite trauma White area on buccal mucosa Clinical appearance where the teeth occlude LeukoplakiaWhite adherent patch or Punch or shave biopsy plaque on oral mucosa that does not rub off Thrush White adherent patch or Clinical appearance and plaque on oral mucosa that potassium hydroxide rubs off (KOH) preparation

Reassurance Surgical excision or cryotherapy with liquid nitrogen Antifungal suspension or troches

Treatment
CUTANEOUS LICHEN PLANUS Cutaneous lichen planus may resolve spontaneously within one to two years, although lichen planus affecting mucous membranes may be more persistent and resistant to treatment. Recurrences are common, even with treatment. Table 4 summarizes the treatment of

nongenital cutaneous lichen planus lesions. High-potency topical corticosteroids are first-line therapy for cutaneous lichen planus.1416 Oral antihistamines (e.g., hydroxyzine [Vistaril]) may be used to control pruritus. Hypertrophic lesions are treated with intralesional triamcinolone acetonide (Kenalog), 5 to 10 mg per mL injection (0.5 to 1 mL per 2-cm lesion).14
Table 4. Treatment of Nongenital Cutaneous Lichen Planus Lesions

Treatment

Dosage

Comments

Cost of generic*

High-potency Administered twice daily topical corticosteroids Oral corticosteroids 30 to 60 mg daily for three to (prednisone) six weeks, then dose is tapered over the next four to six weeks Phototherapy 30- to 40-minute treatments, two or three times weekly

First-line therapy

$12 to $68 for 60 g

For severe, widespread lichen $16 to $20 planus per month For severe disease; narrow- band ultraviolet B is preferred over psoralen plus ultraviolet A

note: Acitretin (Soriatane) is used in more severe cases of cutaneous lichen planus that do not respond to topical treatment; this is an off-label use. Referral to a dermatologist is warranted for patients requiring systemic therapy with acitretin or an oral immunosuppressant. *Estimated retail price based on information obtained at http://www.drugstore.com (accessed February 22, 2011). Acitretin (Soriatane) is an expensive and toxic oral retinoid that is used in more severe cases of cutaneous lichen planus that do not respond to topical treatment.14 Acitretin is a strong teratogen that remains in the body for at least three months after the last dose; therefore, women who may become pregnant are not candidates for the therapy. Acitretin is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of lichen planus, and the label includes an FDA boxed warning recommending that it be used only by physicians with experience treating severe psoriasis, prescribing oral retinoids, and handling teratogenic medications. Referral to a dermatologist is warranted for patients with severe lichen planus requiring systemic therapy with acitretin or an oral immunosuppressant. For genital lichen planus lesions, triamcinolone ointment (Triderm) is a good firstline agent. Topical tacrolimus (Protopic) and clobetasol (Temovate) appear to be effective treatments for vulvovaginal erosive lichen planus.17 Aloe vera gel has been deemed a safe and effective treatment for patients with vulvar lichen planus.18 Topical lidocaine (Xylocaine) may be used as needed for pain relief, and a water-based lubricant may be used to prevent pain during intercourse.

The scarring alopecia of lichen planopilaris is difficult to reverse. A case series showed that topical high-potency corticosteroids and intralesional corticosteroids are commonly used.13 ORAL LICHEN PLANUS Various treatments have been employed to treat symptomatic oral lichen planus, but complete resolution is difficult to achieve.19 Table 5 summarizes treatment options for oral lichen planus. Topical corticosteroids are first-line therapy.1416 High-potency topical steroids are the most effective, with response rates up to 75 percent compared with placebo.20 Topical corticosteroids are also first-line therapy for mucosal erosive lichen planus.14 High-potency corticosteroids applied to the oral mucosa do not appear to cause significant adrenal suppression, even with relatively long-term use. Systemic corticosteroids, such as oral prednisone, should be considered only for severe, widespread oral lichen planus and for lichen planus involving other mucocutaneous sites.10,14
Table 5. Treatment of Oral Lichen Planus

Treatment

Comments

Cost of generic (brand)*

High-potency topical corticosteroids Clobetasol (Temovate) Fluocinonide

First-line therapy

Topical calcineurin inhibitors Pimecrolimus (Elidel) Tacrolimus (Protopic)

For cases unresponsive to topical corticosteroids

Oral corticosteroids (prednisone) For severe, widespread lichen planus

Clobetasol 0.05% ointment: $30 ($205) for 60 g Fluocinonide 0.05% Gel: $38 for 60 g (NA) Ointment: $34 for 60 g (NA) Pimecrolimus 1% cream: NA ($203 for 60 g) Tacrolimus 0.1% ointment: NA ($243 for 60 g) $16 to $20 per month (NA)

NA = not available. *Estimated retail price based on information obtained at http://www.drugstore.com (accessed February 22, 2011). Generic price listed first; brand price listed in parentheses. Applied twice daily. 30 to 60 mg daily for three to six weeks, then tapered over the next four to six weeks. Topical calcineurin inhibitors, such as tacrolimus and pimecrolimus (Elidel), are second-line therapies for oral lichen planus. 15,21 A comparative study showed that topical tacrolimus is

as effective as the high-potency corticosteroid clobetasol in the treatment of oral lichen planus.15,21 A randomized controlled trial revealed that pimecrolimus 1% cream effectively treats erosive oral lichen planus with long-lasting therapeutic effects.22 In a randomized controlled trial, aloe vera gel was significantly more effective than placebo in the clinical and symptomatologic improvement of oral lichen planus.23 If topical corticosteroids are ineffective, carbon-dioxide laser evaporation can lead to long-term remission of symptoms, and may be appropriate as first-line therapy in patients with painful oral lichen planus.24

The Authors RICHARD P. USATINE, MD, is a professor in the Department of Family and Community Medicine and in the Division of Dermatology and Cutaneous Surgery at the University of Texas Health Science Center in San Antonio. MICHELLE TINITIGAN, MD, is an assistant professor at the University of California, San Francisco, Family Medicine Center at Lakeshore. At the time this article was written, she was a resident at the University of Texas Health Science Center. Address correspondence to Richard P. Usatine, MD, at usatine@uthscsa.edu. Reprints are not available from the authors. Author disclosure: No relevant financial affiliations to disclose.

Background
Lichen planus (LP) is a pruritic eruption commonly associated with hepatitis C. Lesions are characteristically papular, purple (violaceous color), polygonal, and peripherally located (eg. on the distal extremities). LP may also affect the genitalia or mucous membranes. It is most likely an immunologically mediated reaction, though the pathophysiology in unclear. See Oral Lichen Planus for more information on this variant of lichen planus.

Pathophysiology
Lichen planus is a cell-mediated immune response of unknown origin. It may be found with other diseases of altered immunity; these conditions include ulcerative colitis, alopecia areata, vitiligo, dermatomyositis, morphea, lichen sclerosis, and myasthenia gravis. An association is noted between lichen planus and hepatitis C virus infection,[1, 2, 3, 4] chronic active hepatitis, and primary biliary cirrhosis.[5] In one meta-analysis, 16% of patients with LP had hepatitis C infection.[2] This association has been shown to exist in all regions of the world, including North America.[3] A workup for hepatitis C should be considered in patients with widespread or unusual presentations of lichen planus. Onset or exacerbation of lichen planus has also been linked to stressful events.[6]

Epidemiology
Frequency
United States

Lichen planus is reported in approximately 1% of all new patients seen at health care clinics. Some areas have reported a higher incidence in December and January.
International

No significant geographical variation in frequency exists for lichen planus.

Mortality/Morbidity
In lichen planus, atrophy and scarring are seen in hypertrophic lesions and in lesions on the scalp. Cutaneous lichen planus does not carry a risk of skin cancer, but ulcerative lesions in the mouth, particularly in men, do have a higher incidence of malignant transformation. However, the malignant transformation rate of oral lichen planus is low (< 2% in one report).[7] Vulvar lesions in women may also be associated with squamous cell carcinoma.

Race
No racial predispositions have been noted for lichen planus.

Sex

No significant differences in incidence for lichen planus are noted between male and female patients, but in women, lichen planus may present as desquamative inflammatory vaginitis.[8]

Age
More than two thirds of lichen planus patients are aged 30-60 years; however, lichen planus can occur at any age.[9]
Proceed to Clinical Presentation