Psoriasis

Psoriasis is a common T-cell–mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Plaques are well-circumscribed and salmon-colored, with silvery scales. Plaques commonly appear on the scalp and extensor surfaces of the extremities. Diagnosis is clinical. Treatment options are determined by the percentage of body surface area (BSA) affected and include topical corticosteroids, retinoids, calcineurin inhibitors, disease-modifying antirheumatic drugs (DMARDs), biologics, and phototherapy.

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Overview

Epidemiology

  • Relatively common in children and adults
    • 0.5%–11% of people worldwide
    • 1%–3% of people in the United States
  • Can be seen at any age, but incidence peaks at the ages of 20–30 and 50–60 (median age is 28 years)
  • ⅓ of patients have a first-degree relative with the disease.
  • Seasonal variation: worse in winter than summer
  • Slightly more prevalent in women
  • Men are more likely to have ocular disease.
  • More common in Caucasians

Etiology

  • Genetic predisposition
    • Major histocompatibility complex (MHC) genes → psoriasis-susceptibility locus (PSORS1)
    • HLA-B27 → psoriatic arthritis
  • Environmental triggers
    • Infections → erythrodermic and plaque psoriasis
      • Streptococcus → guttate psoriasis
      • Human immunodeficiency virus (HIV) → erythrodermic psoriasis
    • Cold weather
    • Trauma 
    • Medications:
      • Lithium, beta-blockers, and antimalarials are the most common. 
      • Interferon-alpha, tumor necrosis factor (TNF)-alpha inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) may also contribute.
      • Corticosteroid use → pustular and erythrodermic psoriasis
    • Alcohol and tobacco use
    • Obesity
    • Smoking
    • Pregnancy
    • Stress

Pathophysiology

Psoriasis is a complex disease marked by a deregulated T-cell–mediated inflammatory process, resulting in keratinocyte proliferation and dysfunctional differentiation.

  • Not completely understood
  • Initiation phase: keratinocytes respond to a trigger → stimulate dendritic cells → cytokine production → T-helper cell differentiation 
  • Maintenance phase: T-helper cells release cytokines → activate keratinocyte proliferation → activate more inflammatory cells, resulting in a self-amplifying inflammatory response
  • Leads to:
    • Epidermal hyperplasia (acanthosis)
    • Accelerated cell turnover → cell retention of nuclei in the stratum corneum (parakeratosis)
    • Keratinocytes fail to release lipids needed for cell adhesions → leads to flaking, scaly plaques
    • Microabscesses
    • Vascular engorgement from superficial blood vessel dilation

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Clinical Presentation

Major subtypes

  • Chronic plaque psoriasis 
    • Most common form (approximately 80% of cases)
    • Symmetric, well-defined, salmon-colored plaques 
    • Thick, silvery scales 
    • Pruritus
    • Most common locations:
      • Elbows (extensor side) 
      • Knees (extensor side) 
      • Scalp 
      • Umbilicus 
      • Gluteal cleft
    • Classification based on body surface area (BSA):
      • Mild-to-moderate disease → < 5% 
      • Moderate-to-severe disease → > 5% 
    • Nail involvement is common.
    • Auspitz sign: pinpoint bleeding with the removal of scales
    • Koebner phenomenon: lesions induced by trauma, such as scratching
  • Guttate (“drop-like”) psoriasis 
    • Acute eruption of multiple small, salmon-colored papules
      • 1–10 mm in size
      • Appear as “dew drops” with fine scales
    • Found on the trunk and proximal extremities
    • Strong association with streptococcal infections
  • Pustular psoriasis 
    • Painful patches or plaques 
    • Localized: primarily involves the palms and soles
    • Generalized annular: 
      • Recurring, subacute eruption of annular erythematous plaques
      • Peripheral pustules and scale
    • Von Zumbusch variant: 
      • Widespread, painful erythematous patches with pinhead-sized pustules
      • Patients may have fever, malaise, leukocytosis, and hypocalcemia.
      • Can have mucosal involvement
      • Life-threatening complications: sepsis, neutrophilic cholangitis, pneumonitis, and acute respiratory distress syndrome
    • In pregnancy, the condition is known as impetigo herpetiformis.
  • Erythrodermic psoriasis 
    • Uncommon
    • Can be acute or chronic
    • Generalized erythema with varying scaling
    • Affects the entire body surface → ↑ risk of complications due to loss of skin barrier
      • Sepsis → fever and chills
      • Fluid loss → dehydration and electrolyte imbalance

Special sites

  • Inverse (intertriginous) psoriasis 
    • Found on intertriginous areas: 
      • Inguinal
      • Perineal and genital 
      • Intergluteal 
      • Axillary 
      • Inframammary
    • Symmetric, smooth, shiny, erythematous plaques
    • Does not usually have a scale due to the moistness of the area
  • Nail psoriasis
    • Tiny pits across the nail are characteristic.
    • Other findings:
      • Leukonychia (white lines or dots appearing on the nail)
      • Lunula red spots 
      • Onycholysis (painless detachment from the nail bed)
  • Palmoplantar psoriasis
    • Involves the palms or soles
    • Erythematous, hyperkeratotic plaques
    • Can have painful fissures

Associated disorders

  • Psoriatic arthritis
    • Seen in up to 30% of patients with psoriasis
    • Can be disabling
    • Symptoms: 
      • Joint pain
      • Back pain
      • Morning joint stiffness
    • Exam findings:
      • Distal arthritis, particularly of the distal interphalangeal (DIP) joints
      • Enthesitis (inflammation at site of tendon insertion) 
      • Tenosynovitis (inflammation of the fluid-filled sheath surrounding a tendon)
      • Dactylitis (“sausage digits”)
      • Arthritis mutilans (resorption of bones leading to soft tissue collapse)
      • Spondyloarthropathy
  • Ocular disorders
    • Blepharitis (inflammation of the eyelid)
    • Conjunctivitis
    • Xerosis (dryness)
    • Corneal lesions 
    • Uveitis
    • Associated symptoms: 
      • Ocular discomfort 
      • Red eyes 
      • Swollen eyelids 
      • Flaking or crusting in eyelashes 
      • Visual changes 
      • Psoriatic lesions on lids
  • Comorbidities: 
    • Obesity 
    • Metabolic syndrome 
    • Hypertension 
    • Diabetes 
    • Atherosclerotic disease
    • Inflammatory bowel disease 
    • Malignancy 
    • Serious infections 
    • Autoimmune disorders

Diagnosis

Diagnosis is established by the clinical history and physical examination findings.

  • Skin biopsy
    • May be used for confirmation, but is rarely necessary 
    • Findings:
      • Acanthosis with elongated rete ridges
      • Parakeratosis 
      • Neutrophilic microabscesses (Munro’s microabscess)
      • Thinned, or absent, granular cell layer 
      • Dilated dermal papillary capillaries
    • Periodic acid-Schiff-diastase (PAS-D) → rule out superficial fungal infection
  • Screening and diagnosis of psoriatic arthritis
    • Physical exam findings
    • Negative rheumatoid factor
    • ↑ erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
    • HLA-B27 testing (helpful if skin lesions are absent)
    • Radiographs of affected joints and spine 
      • Periarticular erosions and bone resorption → “pencil-in-cup” appearance
      • Bone proliferation → “fuzzy” appearance to the bone around the joint
      • Osteolysis and articular collapse → arthritis mutilans
      • Sacroiliitis
Erythrodermic psoriasis

Histopathology from a punch biopsy showing characteristic findings of psoriasis: (a) Munro’s microabscesses, hyperkeratosis, hypogranulosis, parakeratosis, acanthosis with an elongation of rete ridges, and dilated blood vessels; (b) subepidermal blister filled with serous exudate.

Image: “Characteristics of skin histopathology” by Department of Dermatology, Qianfoshan Hospital, Shandong University, Jinan 250014, China. License: CC BY 2.0

Management

Treatment is based on severity, lesion distribution, type, comorbidities, and response.

Treatment based on severity

  • Mild-to-moderate disease:
    • Topical corticosteroids (hydrocortisone, triamcinolone, fluocinonide)
    • Vitamin D analogs (calcitriol, calcipotriene) 
    • Topical retinoids (tazarotene)
    • Coal tar 
    • Phototherapy 
    • Calcineurin inhibitors (tacrolimus, pimecrolimus)
  • Moderate-to-severe disease:
    • Retinoids 
    • Methotrexate
    • Cyclosporine
    • Apremilast (phosphodiesterase inhibitor)
    • Biologic agents (note: TNF-alpha agents can also exacerbate psoriasis)
    • Phototherapy

Adjuvant therapy

  • Emollients
  • Lifestyle modifications 
    • Weight loss 
    • Stress reduction
    • Smoking cessation

Additional considerations

  • Inverse psoriasis:
    • Low-potency corticosteroids 
    • Affected areas have an increased risk for corticosteroid-induced cutaneous atrophy.
  • Guttate psoriasis may resolve spontaneously without intervention.
  • Pustular and erythrodermic psoriasis: hospitalization for severe disease and complications
  • Patients may have refractory disease or suffer multiple relapses. 
  • Goal of treatment is an approximately 75% reduction of psoriasis, or a reduction to < 3% of BSA.

Psoriatic arthritis

  • Pharmacologic therapy: 
    • NSAIDs for mild disease 
    • Biologics (infliximab, etanercept, adalimumab) 
    • Disease-modifying antirheumatic drugs (methotrexate, leflunomide) 
  • Nonpharmacologic therapy: 
    • Physical and occupational therapy 
    • Exercise 
    • Orthotics 
    • Joint protection
    • Weight reduction

Differential Diagnosis

  • Atopic dermatitis: a chronic inflammatory disease of the skin, usually due to a combination of genetics, immunologic dysfunction, and environmental factors. Patients will have pruritus and erythematous lesions on flexural surfaces, often with an exudative or weeping appearance. Silver scales are not present. Diagnosis is based on history and exam, and will differentiate the condition from psoriasis. Treatment includes trigger avoidance, moisturizers, and topical steroids. 
  • Tinea corporis: a superficial cutaneous fungal infection. Skin examination will reveal a pink annular patch with a scaling border and central clearing. Nail lesions may also be seen. These signs are not typically found in the characteristic locations of psoriasis. Diagnosis is mostly clinical. Skin scrapings can be taken for potassium hydroxide (KOH) preparation, which will show segmented hyphae. Treatment includes topical or systemic antifungal medications.
  • Nummular dermatitis: inflammation of the skin, often seen in older patients, and associated with dry skin. Exam will show pruritic, round, erythematous plaques on extensor surfaces that resemble psoriasis; however, these plaques are not typically scaly. Diagnosis is clinical, and treatment includes topical corticosteroids, phototherapy, and supportive care.
  • Seborrheic dermatitis: inflammation of the skin in regions with a high sebaceous gland density. The cause is unknown. Patients may present with scaling on the scalp and pruritis. Red papules with yellow scales may also be seen. Seborrheic dermatitis can coexist with psoriasis, and the diagnosis is clinical. Topical antifungals, corticosteroids, and calcineurin inhibitors may be used for treatment.
  • Pityriasis rosea: a self-limited inflammatory disease due to a viral infection (usually herpes virus). Patients will present with pruritic, salmon-colored, oval plaques with scaling on the periphery. Pityriasis rosea is characterized by a single herald patch, followed by a “Christmas tree” pattern on the back. Diagnosis is clinical and will differentiate the condition from psoriasis. There is no specific treatment, so the focus is on symptom management with topical corticosteroids and antihistamines.
  • Lichen planus: a recurrent, idiopathic inflammatory condition that presents with pruritic, polygonal, purple papules and scaly plaques, which may be located on the wrists, lower legs, genitalia, and oral mucosa. Diagnosis is made based on clinical findings and biopsy, which will also show hyperkeratosis, but the condition does not have parakeratosis like psoriasis. Treatment includes steroids, retinoids, immunosuppressants, and phototherapy.
  • Secondary syphilis: a sexually acquired infection due to Treponema pallidum that can lead to a systemic illness. Findings include a diffuse, symmetric, scaly macular, papular, or pustular rash that is copper-colored, and can include the palms and soles. These plaques are generally smaller than in psoriasis. Diagnosis is made with a positive rapid plasmin reagin (RPR), and spirochetes may be seen on biopsy. Penicillin G is the standard treatment.
  • Lichen simplex chronicus: skin changes that occur from excessive scratching. An underlying cause of pruritus is usually present. Plaques of thickened skin can develop with overlying scale and hyperpigmentation, causing confusion with psoriasis. Areas that the patient cannot reach will appear normal, which helps distinguish the 2 conditions. Diagnosis is clinical and treatment focuses on relieving pruritis with corticosteroids and antihistamines.
  • Reactive arthritis (Reiter’s syndrome): an acute spondyloarthropathy that develops due to a gastrointestinal or genitourinary infection. Patients may have psoriasiform skin lesions, asymmetric oligoarthritis of large joints, and constitutional symptoms. The joints affected differ from psoriatic arthritis. Diagnosis is based on symptoms, exam findings, and the presence of an antecedent infection. Management includes treating the infection, NSAIDs, steroids, and immunosuppressants.

References

  1. Habashy, J., Robles, D.T. (2019). Psoriasis. In James, W.D. (Ed.), Medscape. Retrieved November 3, 2020, from https://emedicine.medscape.com/article/1943419-overview
  2. Feldman, S.R. (2019). Psoriasis: Epidemiology, clinical manifestations, and diagnosis. In Ofori, A.O. (Ed.), Uptodate. Retrieved November 3, 2020, from https://www.uptodate.com/contents/psoriasis-epidemiology-clinical-manifestations-and-diagnosis
  3. Kalb, R.E. (2019). Pustular psoriasis: Pathogenesis, clinical manifestations, and diagnosis. In Ofori, A.O. (Ed.), Uptodate. Retrieved November 3, 2020, from https://www.uptodate.com/contents/pustular-psoriasis-pathogenesis-clinical-manifestations-and-diagnosis
  4. Feldman, S.R. (2020). Treatment of psoriasis in adults. In Ofori, A.O. (Ed.), Uptodate. Retrieved November 3, 2020, from https://www.uptodate.com/contents/treatment-of-psoriasis-in-adults
  5. Hawkes, J.E., & Duffin, K.C. (2020). Erythrodermic psoriasis in adults. In Ofori, A.O. (Ed.), Uptodate. Retrieved November 3, 2020, from https://www.uptodate.com/contents/erythrodermic-psoriasis-in-adults
  6. Mehlis, S. (2020). Guttate psoriasis. In Ofori, A.O. (Ed.), Uptodate. Retrieved November 3, 2020, from https://www.uptodate.com/contents/guttate-psoriasis
  7. Das, S. (2019). Psoriasis. [online] MSD Manual Professional Edition. https://www.msdmanuals.com/professional/dermatologic-disorders/psoriasis-and-scaling-diseases/psoriasis

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