1.5.1 Psoriasis

Psoriatic Disease (PsD).

Psoriasis affects about 125 million people worldwide. About 2-4% of the population in western countries are psoriatic patients with different degrees of clinical manifestation. The prevalence rates are influenced by genetic background, age and geographic as well as environmental factors. Prevalence is higher in adults (from 0.9% to 8.5%) as compared with children (from 0% to 2.1%) with a dual peak of incidence: 30–39 years (type I) and > 40 years of age (type II). In adults, the incidence of psoriasis varies from 30.3 per 100, 000 person years (95% CI 26.6 to 34.1) in Taiwan to 321.0 per 100, 000 person years in Italy. The prevalence of psoriasis varies from 0.14% in east Asia to 1.99% (0.64% to 6.60%) in Australasia. The prevalence of psoriasis is also high in Western Europe (1.92%, 1.07% to 3.46%), Central Europe (1.83%, 0.62% to 5.32%), North America (1.50%, 0.63% to 3.60%), and high income southern Latin America (1.10%, 0.36% to 2.96%). Age stratification within gender shows a higher incidence in females, 18 years old, and conversely a lower incidence in males 18 years old. About 20-30% of psoriatic patients develop sero-negative arthritis. In 2014 the World Health Organization recognised psoriasis as a serious non-communicable disease (WHO report 2016) belonging to the ten most important chronic diseases.

There is evidence from genetic studies that susceptibility to psoriasis involves both the adaptive and innate immune system. Activation of both is found in psoriatic skin. While adaptive immune responses predominate in chronic plaque psoriasis, innate and auto-inflammatory responses dominate in pustular forms of psoriasis.

• Lesion course runs from initiation to propagation to resolution.

• Psoriasis shows a polygenic inheritance. Genome-wide association studies report that the histocompatibility complex HLA-C*06:02 (previously known as HLA-Cw6) is associated with early- onset psoriasis and guttate psoriasis. This major histocompatibility complex is not associated with arthritis, nail dystrophy or late-onset type II psoriasis. PSORS1 in the HLA-C region is located at chromosome 6p21.3. There are 15 so called PSORgenes.

• Genotype and exogenous factors (e.g. local effects like Köbner’s phenomenon or systemic ones) are responsible for the phenotypic expression.

• Psoriasis is multifactorial but a IL23/IL-17 axis centric disease with IL-36 feed forward amplification. It is classified today as an immune-mediated inflammatory disease (IMID). Pathomechanisms show that Th17 cells play a key role. Th17 development is under control and maintained by interleukin IL-23 mainly produced by dendritic cells. Null-Th17 cells, however, produce various cytokines, including IL-17A, IL-17F and IL-23, IL-22. IL-17A and IL-22 induce not only keratinocyte proliferation, but also tumor necrosis factor (TNF)-a. TNF-a accelerates the infiltration of inflammatory cells including lymphocytes, monocytes and neutrophils from the peripheral blood into skin followed by dendritic cell activation. The levels of Th1 cytokines, such as gamma-interferon (IFN-gamma), tumor necrosis factor-a (TNF-a) and interleukin IL -12, are elevated in psoriatic lesions, while increased expression of Th2 cytokines (IL-4, IL-5 and IL-10) is not observed. IL-23p19 and IL-12p40 (IL-12/23p40) are overexpressed in psoriatic skin lesions. The more IL-36 is produced in the lesion course the more neutrophilic cells invade and pustular patterns develop. In addition, antimicrobial peptides are over-expressed in psoriatic skin lesions, and the antimicrobial peptide, LL-37, activates dendritic cells, which leads to the development of inflammation. Furthermore, activation of nuclear factor-kappa B signal induces the expression of keratins 6 and 16 in keratinocytes, which are associated with acanthosis and reduced turnover time in the epidermis.

• The interaction between the epidermis and immune system, specifically T-lymphocytes and cytokines (TNF-alpha, IL2, IL8) leads to epidermal hyperkeratosis with abnormal differentiation of the epidermis.

• Provocation factors are closely related to manifestation and course of the disease: physical, chemical and metabolic factors. Certain inflammatory diseases (dermatoses) and medications (lithium, chloroquine, beta-blockers, interferon-alpha), infections (streptococci, HIV) and stress provoke or maintain the disease.

• Common symptoms of psoriasis include intense itch, pain and scaly skin lesions that can crack and bleed. Predilections are often scalp, elbows and knees and rima ani as well. The following signs (so called Koebnerization effects) can help to confirm a psoriatic lesion:

• Candle sign: Production of candle-grease-like scale when scraping a plaque with curette.

• Auspitz sign: appearance of punctate bleeding when psoriasis scales are scraped away.

Certain features are mostly or often to be seen:

• Circumscribed erythematous plaques with silvery scales of different size and thickness ranging from guttate to large geographic like lesions.

  • Pustules may appear on site of lesions or primarily (pustular psoriasis)

  • Pitted nails or yellowish discolouring (oil patch) and / or dystrophic nails.

  • Palmo-plantar hyperkeratosis

  • Often gyrate pattern on the tongue

Historically, disease classification has been based on clinical appearance, mainly differentiating according to localization and morphology. The recent last classification proposed by the International Psoriasis Council identifies four main forms of psoriasis:

• a. plaque-type, b. guttate, c. general pustular psoriasis (GPP), and d. erythroderma. In addition, several further sub-phenotypes according to distribution (localized vs. widespread), anatomical localization (flexural, scalp, palms/soles/nail), size (large vs. small) and thickness (thick vs. thin) of plaques, onset (early vs. late), and disease activity (active vs. stable) are classified.

Another classification of clinical manifestations:

• Type I psoriasis <40 years, HLA system associated

• Type II psoriasis >40 years

• Clinical variants: guttate psoriasis (acute exanthematous), plaque-type psoriasis (chronic, unstable or static)

• Special forms:

  • Psoriatic erythroderma

  • Pustular psoriasis

    • Generalised pustular psoriasis, Zumbusch type

    • Psoriasis with acute pustules (sudden erupting pustules in pre-existing psoriasis vulgaris).

    • Acral pustular disorders: Palmoplantar pustulosis (PPP), Acrodermatitis continua, Hallopeau type

    • Special type: Impetigo herpetiformis

  • Psoriatic arthritis (HLA-B27): different sub-phenotypes with localization at vertebrae, iliosacral joints, finge

Currently, there is no specific blood test for psoriasis. However, according to co-morbidities, laboratory workup including differential CRP, blood count, kidney-, liver- and lipid values may be examined. Others include tests for hypertension, tachyarrhythmia, diabetes mellitus, gout and/or quality of life questionnaires. Association with inflammatory bowel disease should be ruled out. A skin biopsy should be taken if uncertain type of lesions occurs or other differential diagnoses have to be excluded.

In general, the course is chronic-recurrent or chronic-persistent.

Acute eruptions such as the guttate forms sometimes clear with complete resolution (streptococcal infection, drug cessation). Chronic plaque like forms may suddenly show exacerbations with disseminated guttate lesions or becoming more inflammatory and growing in size. Certain drugs (i.e. ß-blocker, ACE`s, lithium, chloroquine) and infections (i.e.streptococci, HIV, syphilis, mycoses, yersinia) or contact allergens (nickel, chromate, epoxides) may trigger the lesions. Patients with psoriasis in general have a higher incidence rate of serious infection compared with those without psoriasis. Both, drugs and infections may initiate, trigger, exacerbate or maintain psoriasis courses.

Because of co-morbidities psoriasis is associated with a reduced life span. In particular, chronic widespread courses and specific localisations such as face, hands, scalp and genitalia reduce the quality of life. Chronic scalp involvement may lead to hair loss and scarring. Nails can produce disabling features and may become infected with dermatophytes or with other mycotic types. Non-melanoma skin cancer can arise in patients long-term treated by natural or artificial UV-light (photochemotherapy) or cytotoxic agents. Systemic cancer incidence shows a small risk of increase and is associated with severe type and long-term courses and co-morbidities. Lung cancer and CTCL type of lymphoma are statistically relevant but not colon, breast or prostate cancer.

Prevention

In general, there is no primary prevention. Secondary preventions are related to avoidance of infectious triggers, drug provocation, mechanical Koebnerization, daily moisturing of the skin and avoiding of stress and reactive depressive mood swings. Diets are evidenced based. Patient associations can give help.

Therapy

In general, the type of psoriasis, acute or non-acute, localisation, age and profession, adherence and quality of life, co-morbidities and additional arthritis, all have to be considered individually in each patient.

Topical therapy

Topical therapy is indicated when less than 10% of body surface is involved or PASI score is < 10.

However, certain localisations such as face, scalp, nails and hands may lead to combined topical and systemic modalities including UV light sources.

• Salicylic acid in varying concentrations depending on localisation and age (cave resorption in childhood)

• Dithranol 0.03-2% in vaseline or zinc paste (overnight or minute therapy)

• Topical corticosteroids, especially higher potency

• Vitamin D3 and its analogues (calcipotriol, tacalcitol)

• Combination of betamethasone and calcipotriol

• Vitamin-A acid derivatives (tazarotene gel)

• Crisaborole (PDE4 inhibitor)

• UV light therapy regimen such as photo bath therapy 15% NaCl + UVB; Phototherapy (UVA +) UVB/narrow band UVB 311 nm;

Photochemotherapy: 8-(5-) MOP + UVA (PUVA) via a topical cream, via full skin surface bathing (bath PUVA) or systemic oral intake.

A topical aryl-hydrocarbon inhibitor (topinarof) is already launched in the US market.

Systemic treatment:

To qualify for systemic therapy, patients must meet one or more of the following criteria according to the most recent recommendations of the International Psoriasis Council:

1. Psoriasis lesions on 10% or more of their body surface or

2. Psoriasis lesions on sensitive areas of the body (i.e. hands/feet, face, genitals, scalp) or

3. Topical therapy failed to control symptoms.

Scoring systems such as PASI score and QoL are additionally used.

1. Methotrexate oral or subcutaneous

2. Retinoids e.g. acitretin

3. Ciclosporin (A)

4. Fumarates

5. Biologics

   anti-TNF alpha agents (adalimumab, etanercept, infliximab) and biologics directly target certain important pathphysiologic molecules such as anti-IL-12/23p40 antibodies (ustekinumab), IL-23 tildrakizumab, guselkumab, risankizumab), Il-17A (brodalimumab, ixekizumab, secukinumab and bimekizumab against 17A and B). Other targets are the phosphodiesterase 4 (PDE 4) inhibited by apremilast. Aryl hydrocarbon receptor (AhR)-modulating topical agents (tapinarof) and topical phosphodiesterase-4 inhibitor (roflumilast) have been recently approved by FDA for the topical treatment of psoriasis. Furthermore, new classes of TYK-2/ JAK-inhibitors (1-3) such as abrocitinib, deucravacitinib, brepocitinib are becoming currently available.

The clinical features of psoriasis have a large varying spectrum of manifestations and co-morbidities. Therefore, despite its nature as a predominantly skin-centred disease, an interdisciplinary approach is recommended. Psoriatic arthritis is not specifically described in this chapter.