Psychological comorbidities commonly associated with psoriasis include anxiety (7% to 48%), depression (9%-55%), suicidal ideation (patients have a 44% higher rate of suicide compared with the general population, those with severe disease have a 69% greater likelihood of attempting suicide, and a 30% greater likelihood of completing suicide thoughts), and stress (6.4% to 16.6%). Patients report that their aesthetic appearance, time-consuming treatment, skin care, and doctors’ appointments are the main drivers of anxiety, depression, and stress. The latter has been implicated in the exacerbation of the disease. Patients report that they feel stigmatised, and as a result, tend to withdraw from interactions with friends and family, resulting in social isolation.^1,2,3,4,5

Physiological impairment

Psoriasis can be classified into cutaneous psoriasis (see below) and systemic psoriasis. Systemic presentation includes for example psoriatic arthritis (PsA), which affects about 5%–40% of patients and frequently leads to physical impairment.^2,4

Acrodermatitis continua of Hallopeau (see below) is a subtype of psoriasis that can lead to manual function impairment. Besides PsA, psoriasis is also associated with different cardiometabolic disorders, which result in high cardiovascular risk and therefore greater mortality.²

Other comorbidities associated with psoriasis include arterial hypertension, diabetes, coronary artery disease, dyslipidaemia, obesity, and metabolic syndrome.²

Psoriasis has been also associated with various sleep disorders. Decreased sleep quality, increased risk of obstructive sleep apnoea syndrome, and more severe symptoms of restless legs syndrome negatively influence patients’ ability to sleep and rest, which in turn exacerbates psychological and physiological health, worsening quality of life (QoL).²

What causes psoriasis?

The exact aetiology is psoriasis is unknown. Psoriasis is classified into two types:^3,4

• Type 1 psoriasis: Associated with a positive family history, starts before age 40 and is associated with HLA-Cw6 (about 30% of patients have a family history)
• Type 2 psoriasis: Not associated with a family history, presents after age 40, and is not associated with HLA-Cw6.

It has been shown that proinflammatory cytokines such as interleukin-23 (IL-23), IL-17, and tumour necrosis factor α (TNF-α) play critical roles in the initiation and maintenance of psoriasis.^3,4

The disease can be triggered by a variety of extrinsic and intrinsic risk factors. In genetically predisposed individuals, various triggering factors – apart from stress - have been reported, including:⁵

• Seasonal factors (9.7% to 13.3%)
• Infection (3.5% to 8.3%)
• Sun exposure (1.3% to 3.5%
• β-blockers (0.9% to 2.3%).

Signs and symptoms

Men and women are equally affected and a bimodal age of onset has been described. The mean age of onset for the first presentation of psoriasis can range from 15 to 20 years of age, with a second peak occurring at 55 to 60 years.^1,3

Psoriasis presents as well-defined erythematous plaques covered with silvery scales commonly over the scalp, and extensors of extremity, particularly over knees, elbows, and lumbosacral region.³

Psoriasis also affects the eyelid, conjunctiva, and cornea giving rise to trichiasis, ectropion, conjunctivitis, and corneal dryness. The most common eye feature is blepharitis, which can lead to cicatricial ectropion, madarosis, and trichiasis. In some cases, anterior uveitis may be seen. Fissured tongue is the most common finding of oral psoriasis and has been reported to occur in 6.5% to 20% of people with psoriasis.³

Cutaneous psoriasis

Cutaneous psoriasis – especially psoriasis vulgaris affecting ~85–90% of patients – is the most common form of the disease. Lesions start as erythematous papules that gradually enlarge into rich red (also referred to as ‘salmon pink’) plaques. The shape of plaque and the amount of scaling are variable, but most lesions are covered by silvery white scaling. When gently scraping the surface, scales fall off like candle wax (wax-spot phenomenon). This is a sign of the parakeratosis and hyperkeratosis of the epidermis. When plaques are scraped deeper, a wet smooth layer can be revealed referred to as the ‘last membrane phenomenon. On the background of the erythematous membrane, pinpoints-like bleeding foci appear known as Auspitz's sign.⁴

Other forms of cutaneous psoriasis include:⁴

• Scalp psoriasis: Clinical features vary from intermittent mild erythematous scaly plaques to total scalp involvement, usually beyond the hairline giving the appearance of bundled hair.
• Nail psoriasis: Mostly presents as nail pitting. Other presentations range from oil drop discoloration, splinter haemorrhaging of the nail bed to crumbling or loosening of the nail plate. Of note, it is an important predictor for PsA. An estimated 50% of patients have nail psoriasis at the time of diagnosis of psoriasis, which contributes to a greater social burden and worsens the quality of life in these patients.
• Guttate psoriasis: More common in children and adolescents than adults and is usually triggered by streptococcal infection. Patients were classically present with numerous, scaly, small ‘drop-like’ papules and plaques that are 0.3cm–0.5cm in diameter. Itch is of various levels and intensity. One-third of guttate psoriasis would develop into chronic plaque psoriasis in later life.
• Pustular psoriasis: Characterised by white sterile pustules, either in generalised or localised distribution. The typical presentation is an eruption of superficial pustules with an erythematous base. Pustular psoriasis is further divided into:
  • Generalised pustular psoriasis (GPP): A neutrophilic autoinflammatory skin disease characterised by widespread sterile pustules, which can occur with or without a history of plaque psoriasis, is often acute onset on formal psoriatic lesions or normal skin, which may be accompanied by systemic inflammation. Other presentations could be geographic tongue, thick and turbid nail plates, and subungual pustules) and localised pustular psoriasis. Generally, the pustules dry out and form crusts, and high fever relives at the same time. But pustules and high fever may recur periodically. Acute flares may be triggered by medication withdrawal (especially systemic withdrawal of corticosteroids), infections, stress, medication, and pregnancy, causing a dramatic reduction in quality of life. Acute GPP could lead to mortality without appropriate treatment because of accompanied infections and multiple systemic function failures.
  • Localised pustular psoriasis includes palmoplantar pustulosis and acrodermatitis continua of Hallopeau (see below).
• Palmoplantar pustulosis (PPP): A rare, chronic, recurrent inflammatory disease that affects palms and/or soles with sterile, symmetrically distributed, erupting pustules that appear on an erythemato-squamous background. Pustules are more likely to occur in the middle and inner part of palms and/or soles and may extend to the dorsal aspect of hands and fingers (or feet and toes). It could persist for years and usually be resistant to treatment, with periods of partial or total remission interrupted by recurrent exacerbations. Nails are often affected, presented with pitting, lateral grooves, longitudinal crests, nail turbidity, nail stripping, and empyema.
• Acrodermatitis Continua of Hallopeau: Presents as a sterile, macroscopically visible pustule, which affects the nail of one or more digits. Manifests with tender pustules and underlying erythema on the tip of a finger, sometimes on the toe. Nails are always involved, if there is no nail involvement, then alternative diagnoses such as PPP should be considered. Pustules may also be present on the nail bed (under the nail plate). Unsuccessful treatment can lead to severe complications such as ongchoptosis and osteolysis, which may result in functional impairments.
• Erythrodermic psoriasis: A rare and severe variant of psoriasis, which presented with generalised (usually involved 90% or more of body surface area [BSA]) erythema, oedema, pruritus, scaling, exudative lesions, and palmoplantar or diffuse desquamation. Always accompanied by systemic symptoms such as chills, fever, dehydration, lymphadenopathy, gastrointestinal malaise, rarely high output heart failure, and cachexia. Due to the dysfunction of the skin barrier, patients can present with high possibilities of severe systemic infection and sepsis, which occasionally could be life-threatening. The course is long and easy to relapse.
• Inverse psoriasis: Also called intertriginous or flexural psoriasis. The lesions typically present as smooth, moist, scaly-less, dark-red patches in the folds or rubbing areas, including the inguinal folds, axillaes, inframammary folds, anogenital areas, umbilicus, and retro-auricular areas such as hip groove, armpit, groin, and under the breast, retro-auricular regions, and glands. It is common to see patients with typically plaque psoriasis lesions localised in other body areas.

The severity of cutaneous psoriasis

Cutaneous psoriasis severity categories are important for clinicians to not only make treatment decisions. Severity can be measured using combined score cards such as BSA, psoriasis area and severity index (PASI), and investigator's global assessment (IGA). Cutaneous psoriasis can be divided into three categories: mild, moderate, and severe (see Table 1).⁴

Table 1: Categories of psoriasis

What treatment options are available?

According to the 2022 European Dermatology Forum treatment guidelines, mild to moderate psoriasis can be adequately controlled with topical therapy alone, while severe disease requires phototherapy or systemic therapy (including biologics).⁶

According to Papp et al, about 50% of psoriasis patients have mild,  78% of have moderate disease and only 2% of patients have severe disease. Therefore, the focus of this article will be on the treatment of mild to moderate disease.⁷

The authors of the 2021 Swiss expert consensus guideline state that the ultimate goal of psoriasis treatment is the complete clearance of all skin symptoms, which is not possible in all patients. Furthermore, caution the authors, clinicians should keep in mind that psoriasis is a chronic and recurring disease, thus requiring life-long treatment.⁸

According to the guideline, the most important guiding principle when deciding on a therapy is patient satisfaction. Therefore treatment decisions should be based on shared-decision making and should include discussion about the time it will take for the treatment to start working and the expected outcome. The authors of the guideline strongly recommend a simple, once-daily treatment regimen that include the following:⁸

1. Emollients: Should be used daily to restore the barrier function of the skin, prevent or interrupt flare-ups, improve skin elasticity, and maintain the balance of the skin’s microbiome. Emollients containing urea 5%–10%, salicylic acid, ceramides, niacinamide, or thermal water have been shown to be beneficial to psoriasis lesional and non-lesional skin.
2. Fixed combination of calcipotriol 50μg/g (Cal) and betamethasone-dipropionate 0.5 mg/g (BD):Used once daily for two to eight weeks. Once the treatment goal of clear/almost-clear skin is achieved, patients can be advised to reduce the frequency of application in a step-wise manner (eg to every other day for another two weeks) and to continue with a maintenance schedule of, for example, a twice weekly application. The benefit of combining Cal and BD is based on the superior efficacy (additive beneficial effect in reducing the hyperproliferation of keratinocytes and inflammation) and their synergistic effect on tolerability (lowering the risk of skin atrophy and reducing burning sensations, respectively), compared to the use of Cal or BD alone.
3. Monotherapy with topical corticosteroids (TCSs) classes III/IV: TCSs have been approved for the treatment of psoriasis vulgaris since 1956 and are among the standard. Recommended as second-line treatment but can be used as first-line treatment in some instances (eg initial treatment for mild psoriasis). According to expert consensus and summary of product characteristics, a continuous, once/twice daily application of class IV TCSs in monotherapy should not exceed four weeks. They can be used in combination with vitamin D₃ TCSs are often available as different formulations (ointments, creams, solutions, lotions, foams, and shampoos), so an individual, patient-preferred application can be selected. In ge­neral, most TCSs are used once daily. Once the treatment goal has been achieved, they should be tapered down slowly. For reasons of practicability, they are usually applied in the evening. Adverse drug reactions depend on the drug class of the preparation as well as the location and duration of its application. In decreasing order of frequency, burning, itching, folliculitis, hypertrichosis, perioral dermatitis, and hypopigmentation may occur. Long-term use of class III/IV TCS can also cause striae, telangiectasia, and skin atro­phy. When applied more frequently and/or on extensive areas and/or under occlusion, a systemic effect of adrenal suppression can occur, which bears the risk of developing rebound or pustular psoriasis when not tapered down slowly.
4. Vitamin D₃ analogues or derivatives (tacalcitol and calcitriol): First approved in 1992 for the treatment of mild to moderate psoriasis vulgaris. These act via specific receptors in the target cells of the skin. Their effect is selective and depends very much on the differentiation level of the keratinocytes. In the case of fast-growing, non-differentiated keratinocytes, vitamin D₃ analogues inhibit further growth. With slow-growing keratinocytes, a proliferation-enhancing effect occurs. Depending on the preparation, vitamin D₃ analogues are applied once or twice daily. When applied according to the current guidelines, the indication is a BSA of up to 10%. Adverse drug effects of vitamin D₃ analogues may occur in the form of local irritation (pruritus, burning, and erythema). Individual cases of hypercalcemia have only been observed in cases where maximum levels are exceeded for longer periods. Vitamin D₃ analogues are therefore suitable for induction and maintenance therapy.

The authors of the Swiss expert consensus guideline recommends that the same therapeutic agents can be used in the maintenance phase (see above) but should be applied less frequently (eg twice a week).⁸

Conclusion

Psoriasis is a chronic disease that negatively affects the QoL of patients. It is associated with psychological and physiological impairments. A simple, once-daily treatment regimen is recommended to improve patient adherence. The 2021 Swiss expert consensus guideline recommends once daily emollients and fixed combination of Cal/BD 50μg/g/0.5 mg/g as first-line therapies.

References

1. Blackstone B, Patel R, Bewley A, et al. Assessing and Improving Psychological Well-Being in Psoriasis: Considerations for the Clinician. Psoriasis (Auckl), 2022.
2. Nowowiejska J, Baran A, Grabowska P, et al. Assessment of Life Quality, Stress and Physical Activity Among Patients with Psoriasis. Dermatol Ther (Heidelb), 2022.
3. Nair PA, Badri T. [Updated 2022 Apr 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448194/
4. Yan B-X, Chen X-Y, Ye L-R, et al. Cutaneous and Systemic Psoriasis: Classifications and Classification for the Distinction. Front Med, 2021.
5. Kaminy K, Kishimoto M, Sugai J, et al. Risk Factors for the Development of Psoriasis. Int J Mol Sci,
6. European Dermatology Forum (2022). Euroguiderm Guideline For The Treatment Of Psoriasis Vulgaris. Systemic Treatment. https://www.edf.one/home/Guidelines/EuroGuiDerm-psoriasis-vulgaris.html
7. Papp KA, Gnaidecki R, Beecker J, et al. Psoriasis Prevalence and Severity by Expert Elicitation. Dermatology and Therapy, 2020.
8. Maul J-T, Anzengruber F, Conrad C, et al. Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway. Dermatology, 2021.