Psoriasis

Psoriasis is a common chronic inflammatory skin disorder affecting individuals with an underlying genetic predisposition. Triggering events (e.g., infection, medication) can lead to disease manifestation. Psoriasis typically manifests as sharply demarcated, erythematous, scaly, pruritic plaques, most commonly occurring on the scalp, presacral region, and extensor surfaces of the knees and elbows; however, any area of the skin may be affected. Other common clinical findings include arthritis, generally affecting the fingers and lower spine, and nail involvement (e.g., pitting, discoloration). The size, location, and severity of psoriasis lesions vary depending on the subtype. The diagnosis is primarily clinical, based on the patient's symptoms, history, and the presence of any specific signs (e.g., the Auspitz sign); a biopsy is rarely indicated. Mild psoriasis can be treated with topical agents such as corticosteroids, whereas moderate to severe disease requires systemic therapy (e.g., phototherapy, biologic agents).

• Prevalence: ∼ 2% of the US population [1][2][3]
• Age of onset: : can present at any age; typically shows bimodal age distribution [1][4]
  • Early onset psoriasis: (∼ 75% of cases): before 40 years of age
  • Late onset psoriasis (∼ 25% of cases): after 40 years of age; usually mild

Epidemiological data refers to the US, unless otherwise specified.

• Genetic predisposition: most likely determined via polygenic inheritance [5]
• Trigger factors [6]
  • Infectious
    • Infections of the upper respiratory tract caused by β-hemolytic streptococci
    • Staphylococcal infections
    • HIV
  • Mechanical irritation
  • Drugs; (e.g., beta-blockers, chloroquine, lithium, interferon)

The mechanism causing the immune response is not yet well understood.

• Increased proliferation of keratinocytes
  • Acanthosis: thickening of the epidermis
  • Parakeratosis: retention of nucleated keratinocytes in the stratum corneum
• T cells secrete cytokines, which mediate an inflammatory response.

References:[7]

The disease course is typically relapsing, with symptom-free intervals.

Cutaneous lesions [2]

• Well-demarcated, erythematous plaques and/or papules with silver-white scaling
• Typically, a few single lesions initially appear, often becoming confluent. [2]
• Located mainly on the scalp, trunk, elbows, and knees (extensor surfaces), but any area of the skin may be affected.
• Pruritus in ∼ 80% of cases (typically mild, but may be severe in some cases) [8]
• Characteristic features may be present.
  • Auspitz sign ; [2]
    • Small pinpoint bleeding when scales are scraped off
    • Removal of the scales exposes the dermal papillae, which leads to bleeding.
  • Koebner phenomenon: Physical stimuli or skin injury (e.g., trauma, scratching, irritating clothing) can lead to the appearance of psoriatic skin lesions on previously unaffected skin (isomorphic response). [2]

Cutaneous variants [2]

• Plaque psoriasis: most common variant; characterized by symmetrically distributed, thick, scaly, erythematous lesions
• Guttate psoriasis
  • Lesions the size of drops of water
  • May develop into plaque psoriasis
  • Occurs mainly in children and adolescents after streptococcal infection
• Erythrodermic psoriasis
  • Generalized erythematous lesion with diffuse scaling
  • May lead to severe illness with fever and dehydration
• Inverse psoriasis: : mainly affects skin folds and flexural creases of large joints (flexural psoriasis)
• Pustular psoriasis
  • High correlation with HLA-B27
  • Generalized pustular psoriasis (most common subtype)
    • Generalized erythroderma, confluent white pustules over the entire body, involvement of the oral mucosa and tongue
    • Relapsing course with pronounced malaise (fever, weakness, chills); may be fatal

Plaque psoriasis is the most common psoriasis variant (accounts for ∼ 80–90% of psoriasis cases). [2]

Erythrodermic and generalized pustular psoriasis can lead to severe, life-threatening illness, which must be treated as a medical emergency. [2]

Nail involvement [2]

Present in ∼ 50% of cases [9]

• Nail pitting: small, round depressions in the nail
• Brittle nails: nail dystrophy with crumbling of the nail
• Onycholysis: partial and mostly distal separation of the nail plate
• Oil drop sign (or salmon spot): well-circumscribed, yellow-red discoloration of the nail [9]

Clinical features vary depending on the cutaneous variant. Erythema, thickening, and scaling are present in most variants. [2]

Definition

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that primarily affects the hands, feet, and/or spine and occurs in up to 30% of patients with psoriasis. [10]

Psoriasis and PsA can occur together or alone

Clinical features [10][11]

Arthritis [10][11]

Multiple patterns may be present.

• Oligoarthritis; (typically asymmetric; ≤ 4 joints affected)
• Polyarthritis (symmetric; similar appearance to rheumatoid arthritis)
• Involvement of distal and proximal interphalangeal joints (DIP and PIP); often occurs in conjunction with other subtypes [10]
• Arthritis mutilans: destruction of interphalangeal joints through bone resorption, resulting in the collapse of the soft tissue of the affected area (e.g., telescoping fingers or “opera glass hand”)
• Axial involvement (spine and sacroiliac joints); often occurs in conjunction with other subtypes

Accompanying features [10]

• Enthesitis, e.g., of the calcaneal tendon or the plantar fascia [10]
• Dactylitis: inflammation and swelling of the fingers and/or toes (“sausage digits”) [10]
• Tenosynovitis
• Nail involvement (e.g., pitting, onycholysis) [2][10]
• Uveitis [10]

In PsA, patterns of joint involvement can change over time and vary widely between patients. Oligoarthritis tends to be more common at onset, while polyarthritis may develop in later stages. [10]

Diagnostics [10][11]

General principles

• Diagnosis is mainly clinical, based on patient and family history and clinical features.
• lmaging studies can support the diagnosis and help estimate severity.
• Laboratory studies are usually obtained as a part of the inflammatory arthritis workup.
• Consult rheumatology for all patients.

Imaging studies [10][11]

• X-ray of the affected area (e.g., hands, spine)
  • Supportive findings include:
    • Fingers: pencil-in-cup deformity of DIP joints
    • Spine: syndesmophytes, asymmetric paravertebral ossification, unilateral sacroiliitis
  • May appear normal in early disease, especially in patients with axial involvement
• Further studies
  • Doppler ultrasound: may show early erosions, synovitis, and enthesophytes
  • MRI: may show focal erosions, synovitis, and/or bone marrow edema

Laboratory studies [10]

Laboratory studies may be obtained to rule out other diagnoses but are not typically required to make a diagnosis of PsA.

• Inflammatory markers: ↑ ESR, ↑ CRP [10]
• BMP: ↑ uric acid
• Serology
  • HLA-B27: present in ∼ 25% of patients [10]
  • ACPA and rheumatoid factor: negative in ∼ 95% of patients [10]

Rheumatoid factor is typically negative in patients with PsA, which can help rule out differential diagnoses of inflammatory arthritis. [10]

Classification criteria

These classification criteria are not diagnostic but can provide guidance in clinical practice. [10]

Management of psoriatic arthritis [11][13]

General principles

• Treatment depends on disease severity and the presence of certain features and/or comorbidities.
• A treat-to-target approach with a target of remission or low disease activity is recommended. [13]
• Consult a rheumatologist before starting pharmacotherapy.

Pharmacological treatment [11][13]

• Disease-modifying antirheumatic drugs (DMARDs): mainstay of treatment for most patients with PsA.
  • Conventional DMARDs, e.g., methotrexate, sulfasalazine, leflunomide
  • Targeted synthetic DMARDs, e.g., apremilast, tofacitinib
  • Biologic DMARDs, e.g.:
    • TNF-α inhibitors (first line), e.g., etanercept, adalimumab, infliximab
    • IL-17 inhibitors, e.g., secukinumab, ixekizumab
    • IL-12/23 inhibitors, e.g., ustekinumab
    • Abatacept
• NSAIDs, e.g., naproxen, indomethacin:
  • May be trialed as initial treatment in patients with very mild disease (limited evidence of efficacy)
  • Preferred over DMARDs in certain patients, e.g., those with axial disease or predominant enthesitis [11]
  • Can also be prescribed for symptomatic relief
• Intraarticular glucocorticoids: used for symptomatic relief

Systemic glucocorticoids are not commonly used in PsA because of concerns that tapering too rapidly may induce a flare of cutaneous disease. [11]

Supportive management [13]

• Encourage lifestyle modifications.
  • Smoking cessation
  • Low-impact physical activity
  • Maintaining a healthy weight
• Recommend physical therapy and occupational therapy.

Psoriasis is a clinical diagnosis based on patient and family history and thorough skin examination.

Approach [2][14]

• Consult a dermatologist to confirm the diagnosis.
• Skin biopsy is not routinely required for diagnostic confirmation.
• Perform an ASCVD risk assessment. [2]
• Evaluate for comorbidities including psoriatic arthritis, IBD, MDD, and anxiety.

All patients with psoriasis should be evaluated for psoriatic arthritis, as early diagnosis improves outcomes and the presence of psoriatic arthritis influences treatment decisions. [2]

Skin biopsy [15]

• Indications: Consider only if clinical presentation is atypical.
• Supportive findings
  • Acanthosis and parakeratosis
  • Thickening of the stratum spinosum, thinning of the stratum granulosum
  • Munro microabscesses: accumulation of neutrophils in the stratum corneum surrounded by parakeratosis

The differential diagnoses listed here are not exhaustive.

The following recommendations apply to the treatment of plaque psoriasis ; consult a specialist before initiating treatment.

Approach to patients with psoriasis[2][14][17]

Treatment depends on disease severity, comorbidities, and patient preference.

• All patients
  • Assess disease severity: e.g., based on estimated body surface area (BSA) affected.
  • Provide supportive care.
• Mild psoriasis (below 3–5% BSA involvement)
  • Topical pharmacotherapy (e.g., corticosteroids, calcipotriene, retinoids) and/or targeted phototherapy
  • Systemic agents if treatment response is insufficient
• Moderate to severe psoriasis (above 3–5% BSA involvement)
  • Systemic pharmacotherapy
  • And/or phototherapy
    • Narrowband UVB therapy
    • PUVA therapy
  • Consider adjunctive topical pharmacotherapy.

All patients with plaque psoriasis and concomitant psoriatic arthritis require systemic treatment. [2]

Topical pharmacotherapy [2][17]

Topical pharmacotherapy is the mainstay of mild psoriasis treatment.

• Topical corticosteroids (first-line: )
  • Face, neck, or skin folds (i.e., areas with sensitive/thin skin): low-potency (e.g., hydrocortisone 1%)
  • Scalp, trunk, and extremities
    • Medium-potency (e.g., triamcinolone 0.1%)
    • High-potency (e.g., fluocinonide 0.05%)
• Topical calcineurin inhibitors (off-label use ): e.g., tacrolimus 0.03 % or 0.1%, or pimecrolimus 1%
  • Alternative to steroids for areas with sensitive/thin skin
  • May be used for maintenance after > 4 weeks of steroid use
• Additional therapy: the following agents may be used in combination with topical corticosteroids
  • Vitamin D analogues: e.g., calcipotriene/calcipotriol
  • Keratolytics: retinoids (e.g., tazarotene), or salicylic acid
  • Tar preparations, e.g., 1% coal tar lotion
  • Anthralin

Commonly used combinations include topical corticosteroids plus either vitamin D analogues or keratolytic agents. Combination therapy increases efficacy and may cause fewer adverse effects than monotherapy.

Systemic pharmacotherapy [18][19]

• Principles of systemic therapy
  • Management should be specialist guided
  • Before therapy initiation, obtain baseline laboratory studies (e.g., BMP, CBC, liver chemistries).
  • Adjunctive topical pharmacotherapy may be added after a careful review for possible interactions.
• Common indications
  • Moderate to severe psoriasis
  • Mild psoriasis with insufficient response to topical agents
• Treatment options
  • Biologics
    • IL-17 inhibitors, e.g., brodalumab, secukinumab
    • IL-23 inhibitors, e.g., ustekinumab , guselkumab
    • TNF-α inhibitors, e.g., etanercept, adalimumab, infliximab
  • Other medications
    • Methotrexate PLUS folic acid to reduce the adverse effects
    • Cyclosporine
    • Apremilast

Supportive care [17]

• Provide topical treatment with ointments (e.g., petroleum jelly) and moisturizers to prevent moisture loss.
• Counsel on reducing alcohol consumption and smoking cessation.
• Provide management for any comorbid mental health conditions (e.g., MDD, anxiety).

Alcohol consumption and tobacco use are associated with increased disease severity and ASCVD risk. [14]

Increased risk of other comorbidities:

• Metabolic syndrome
• Cardiovascular diseases (hypertension, coronary heart disease, myocardial infarction, stroke)
• Chronic kidney disease

We list the most important complications. The selection is not exhaustive.

• Lifelong disease, usually benign
• Patients may experience remissions of varying lengths; acute episodes of exacerbation possible.
• Psoriasis is associated with depression and a decreased quality of life.

• Avoidance of nicotine and alcohol
• Regular physical activity