Psoriasis (Übersicht) L40.-

The word "psora" was used as early as 129-99 p.C. by the Greek physician Galenos (Galen) to describe scaly and itchy skin diseases, although no distinction was made between atopic dermatitis, psoriasis, skin tuberculosis or leprosy. Specifically, the English dermatologist Robert Willan first described psoriasis in 1809. 30 years later it was the Viennese Ferdiand v. Hebra who separated psoriasis from leprosy. In 1879, the German dermatologist Heinrich Köbner described the isomorphic stimulus effect (Köbner phenomenon) named after him in relapsing psoriasis. Originally, this phenomenon was used to distinguish psoriasis from syphilitic infections.

First therapy approaches refer to sunlight in psoriasis. Already in pre-Christian times improvements of "leprosy" under UV influence were described. In the 2nd half of the 19th century, coal tar, chrysarobin, pyrogallol, bea-naphthol, and intramuscularly injected sulfur were used. In the 1st half of the 20th century, the therapeutic spectrum expanded to include radiotherapies, arsenic, artificial UV, intravenous salicylic acid, fever therapies, injections of adrenal extracts, and others.

Common (about 100 million people worldwide are affected), acute or chronic, HLA-associated "inflammatory skin disease" provoked by exogenous and endogenous stimuli, with T-cell-mediated autoimmunesis, occurring at all stages of life and affecting about 2% of the Central European population. Psoriasis is based on a complex genetic predisposition. Familial accumulations are known. Clinically, characteristic localized or generalized papules or plaques are found, emphasized on the extensor side, usually symmetrically distributed, with varying degrees of consistency (palpation firm like leather), sharply demarcated, red or covered with white scales. Rarer are pustules or vesicles. Joint involvement of varying degrees (seronegative polyarthritis) is found in about 20-30% of psoriatic patients. Crohn's disease and uveitis are commonly associated with psoriasis. Due to pathophysiological and genetic similarities, psoriasis can be counted among the group of IMID(Immune-Mediated Inflammatory Diseases).

Clinical variants of psoriasis with sometimes very different courses are:

• Psoriasis plaque type:
  • Psoriasis stationary plaque type(psoriasis vulgaris chronic stationary plaque type)
  • Psoriasis relapsing plaque type(psoriasisvulgaris chronic-active plaque type)
• Alternatively, 2 types of non-pustular psoriasis can be defined:
  • Type I psoriasis (with early onset, <40 years of age, usually familial clustering and HLA-Cw*06.02 allele association)
  • Type II psoriasis (with late onset, >40 years, no familial clustering, no association with HLA alleles)
• Psoriasis guttata (acute, exanthematic psoriasis)
• Psoriasis inversa
  • Psoriasis palmaris et plantaris
  • Psoriasis intertriginosa
  • Erythrodermia psoriatica (psoriatic erythroderma, as a maximum variant of psoriasis vulgaris).
• Pustular psoriasis:
  • Pustular psoriasis (generalized type):
    • Psoriasis pustulosa generalisata
    • Impetigo herpetiformis
    • Erythema annulare centrifugum-like psoriasis.
  • Pustular psoriasis (localized type):
    • Psoriasis pustulosa palmaris et plantaris (Königsbeck-Barber type)
    • Psoriasis pustulosa palmaris et plantaris(pustular bacterid Andrews type)
    • Acrodermatitis continua suppurativa (acral type or Hallopeau type).
• Psoriasis arthropathica
• Special forms of psoriasis:
  • Psoriasis seborrheic type
  • Psoriasis capitis
  • Psoriasis of the nails (nail psoriasis)

The individual clinical forms are defined on the one hand by their course (acute - chronic), on the other hand by the localization (psoriasis inversa, psoriasis palmo-plantaris) or by the occurrence of pustules (psoriasis pustulosa) or by other organ manifestations (psoriasis arthropathica).

The severity of psoriasis can be classified according to the percentage of body surface area affected, BSA: Body Surface Area, or according to the PASI score.

• mild psoriasis: BSA< 2% /(PASI < 5)
• moderate psoriasis: BSA 2-10% /PASI 5-20
• severe psoriasis: BSA> 10% /PASI >20

Current clinical classification of psoriasis (according to guideline)

• mild psoriasis: PASI <= 10/BSA <= 10/ DLQI <= 10
• moderate-severe psoriasis: PASI > 10/ BSA > 10/DLQI > 10

Prevalence of psoriasis in different countries:

• Germany: 1-2% (-3%) of the population. If one parent is affected, the prevalence is around 14%.
• Denmark: 2.9% of the population.
• Sweden: 2.3% of the population.
• USA: 2.2% of the population (various American studies have also described prevalence rates of between 4.0-4.7%).
• China: 1.7% of the population.
• UK: 1.6% of the population.
• Sweden: 1.4% of the population (already mentioned above with other percentages)
• Norway: 1.4% of the population.
• Norwegian Laplanders: 0.6% of the population.
• Spain 1.4% of the population.
• India: 0.7% of the population.
• Africa: 0.4-0.7% of the population.
• East Africa: 0.7% of the population.

Prevalences of 0.1-1.0% are given for children. In a larger collective (n= 293,181 children), the prevalence was 0.45% (Jacobi et al. 2016).

I. Endogenous factors

• Genetics: genetic disposition plays an undisputed role. This is evidenced by familial clustering, as well as by studies of monozygotic twins. In a larger study, 11x concordant behavior was detectable in 15 monogenic twins, 4x discordance. Genome-wide association studies have identified >50 psoriasis-associated gene loci and gene variants to date. Overlaps with other inflammatory diseases are detectable. Genetic markers significantly associated with psoriasis are termed "psoriasis susceptibility loci" - PSORS1- PSORS15 - of which PSORS1 is by far the most important genetic determinant.
• PSORS1 is the main predisposing factor for early life psoriasis with with severe course (type I psoriasis) and reflects the known association with the human leukocyte class I antigen gene(HLA-Cw 06:02).
• HLA associations: proven associations with HLA-B13, HLA-Bw57, HLA-Cw6, HLA-B27 (HLACw1, HLA-DR4 and HLA-DR7). HLA-Cw*06:02 is the main risk allele of psoriasis (early onset/severe course/carriers of this allele are 10x more likely to be affected by psoriasis). HLA-B27 is associated with psoriatic arthritis along with numerous other conditions.
• HLA-Cw6 alle le: The worldwide frequency of the HLA-Cw6 allele varies widely, being generally higher in Caucasians than in Asians (Huang YW et al. 2021). Phenotypically, HLA-Cw6 has been found to be associated with guttate psoriasis. Stress, obesity, and streptococcal pharyngitis are commonly observed in HLA-Cw6-positive patients. Likewise, Köbner's phenomenon may be more common in this population. HLA-Cw6-positive patients appear to respond better to methotrexate and ustekinumab. However, this difference in efficacy of ustekinumab was only moderately detectable in a post-hoc analysis (Chen L et al 2018).
• HLA-Cw1: The prevalence of HLA-Cw6 was much lower expressed than HLA-Cw1 in some Asian countries (Huang YW et al. 2021). HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and axial type of psoriatic arthritis. Furthermore, HLA-Cw1 positive psoriatic patients seem to be more likely to fail to respond to conventional therapies (Huang YW et al 2021).
• HLA-B27: Another HLA class I antigen, HLA-B27 is associated mainly with psoriatic arthritis (+ ankylosing spondylitis+other rheumatic diseases).
• Other susceptibility loci known and defined to date with significant association to psoriasis are:
  • PSORS2/syn. CARD14/(gene locus: 17q24-q25)
  • PSORS3 (gene locus: 4q)
  • PSORS4 (gene locus: 1q21)
  • PSORS5 (gene locus: 3q21)
  • PSORS6 (gene locus: 19p)
  • PSORS7 (gene locus: 1p)
  • PSORS8 (gene locus: 16q)
  • PSORS9 (chromosomal region 4q28-32; associated with early disease onset in the Chinese population)
  • PSORS10 (chromosome 18p11.23)
  • PSORS11 (chromosome region 5q31.1-q33)
  • PSORS12 (chromosome 20q13)
  • PSORS13 (chromosome 6q21)
  • PSORS14 (chromosome 2q14.1)
  • PSORS15 (chromosome 2q36)
• Apparently, a genetic network exists with a variable disease-typical "gene signature" that can be activated by various endogenous or external factors. This gene network is influenced in psoriasis (see also atopic eczema) by inflammatory (Th1 and Th17 cells) cytokines (e.g. interferon gamma/TNF-α/other interleukins). Evidence suggests that a significant predisposition of psoriatic arthritis exists in the presence of a single nucleotide polymorphism of the TNF-α gene. This TNF-α gene polymorphism is also related to the severity of psoriasis or its response to TNF-alpha blockers (e.g., etanercept).
• Antimicrobial peptides (AMP`s): It is well established that overexpression of antimicrobial peptides, especially cathelicidin, beta-defensin 2, psoriasin (=S100A7) and ribonuclease 7(RNAse 7) plays an important role in the pathogenesis of psoriasis (cf. also the low tendency to infections in psoriasis vulgaris!). Thus, it could be shown that the cathelicidin LL37 (s.a. cathelicidins) binds and complexes own cytosolic DNA (these are detected in psoriatic keratinocytes!). The complexes can induce an interferon response with an inflammatory reaction (see below Inflammasome).
• Skin barrier dysfunction: Several gene loci or gene variants affect genes with functions for the skin barrier (e.g. the genes: LCE3A, LCE3B, LCE3C, LCE3Bdel, see also Epidermal differentiation complex). Thus, deletion of LCE3B and LCE3C (LCE3B/C-del) has been shown to be a common psoriasis risk factor. LCE3A is directly adjacent to and functionally linked to LCE3B/C. Functional analyses show that LCE3 proteins and LCE3A in particular, even at low micromolar concentrations, exhibit defensin-like antimicrobial activity against a variety of bacterial taxa.
• Immunological features: Other variations involve genes associated with immune system activation. These include CARD14, NFKBIA, REL, TYK2, IL28RA, TRAF31P2.

II. exogenous factors

• 1. drugs: There is reasonable evidence that various drugs are capable of maintaining or triggering psoriasis vulgaris. These include:
  • Beta-blockers (e.g. propanolol).
  • Calcium channel blockers (e.g., diltiazem)
  • Glucocorticoids (esp. after discontinuation or reduction of therapy)
  • Lithium
  • Antimalarials (e.g. chloroquine)
  • NSAIDs (naprofen, diclofenac, indometacin)
  • various antibiotics (e.g. macrolide antibiotics)
  • Gold
  • In rare cases TNF-alpha blockers for inflammatory bowel disease (see case 2 below)
• 2. local trauma ( Köbner's phenomenon can also be considered mechanical trauma)
• 3. acute dermatitis solaris; dermatitic UV-irradiation can be triggering in relapsing psoriasis (also opposite is reported)
• 4. irritative local therapies
• 5. infections (e.g. streptococcal angina)
• 6. emotional stress

Keratinocytes/keratins: Keratinocyte stimulating mediators (TNF alfa, IL-8, granulocyte macrophage colony-stimulating factor = GM-CSF) result in a proliferation stimulus. The cell cycle of keratinocytes is accelerated more than 8-fold. Cells of the basal cell layer need only 4 days to reach the str. corneum. 25% of keratinocytes (increased 3-fold) are in the proliferative S-cell cycle phase. Such proliferation-promoting mediators are also produced by keratinocytes themselves (interleukins: IL1, IL6, IL8, IL17A, interferon gamma, TNF, transforming growth factor alpha (TGF-alpha) and GM-CSF (see growth factors below). Furthermore, interleukins-17 and -22 are responsible for keratinocyte hyperplasia. These are produced by the Th17 cells. The structural proteins of keratinocytes are also altered (reduction of suprabasal keratins 1 and 10; neoexpression of keratins 6 and 16). The role of the cytokine "thymic stromal lymphopoietin", which is produced in psoriatic keratinocytes, has not yet been definitively clarified. Evidence suggests that TNF-alpha and interleukin1-beta can induce CCL27 in basal keratinocytes.

Autoantigens: Various potential autoantigens, such as ADAMTS-like protein 5 expressed by melanocytes and the antimicrobial peptide LL37, are important for psoriatic inflammation. Both proteins are recognized by TH17 cells after binding to the protein HLA-C*06:02 (see HLA system) and thus initiate psoriatic inflammation. Remarkable is a structural homology of keratin 17 with M-proteins of streptococci. In this respect, keratin 17 also presents itself as a potential autoantigen. Furthermore, heat shock proteins (HSP) seem to play an important role in the pathogenesis of psoriatic inflammation. For example, HSP 90 has been linked to affected cell survival and cytokine signaling in psoriatic patients.

Lymphocyte/homing signaling: Probably at the beginning of the psoriatic inflammatory cascade are activated dendritic cells (DCs) and macrophages, which are stimulated to secrete pro-inflammatory cytokines such as IL-1, IL-6, IL-12, IL-17, IL-23 and TNF-alpha. This activates interferon gamma producing CD4+ T lymphocytes . This process leads to the maturation of naïve T cells into Th17- cells and other inflammatory Th cell populations such as Th-1 lymphocytes (Th1 lymphocytes; no IL-4 production). Th-1 lymphocytes (as well as Th17 cells) play a central role in the pathogenesis of psoriasis (blockade of CD4 T lymphocytes by anti-CD4-AK leads to a clinical improvement of psoriasis, other lymphocyte-suppressive drugs such as ciclosporin, fumaric acid esters, as well as PUVA therapy, among others, also cause this effect). The activated T-lymphocytes receive an "address" through the expression of certain surface markers, which defines the place where they are needed. These so-called "homing" signals, mediated by cutaneous lymphocyte-associated antigens (CLA), enable the lymphocytes to infiltrate both compartments, epidermis and dermis. In psoriatic patients, inflammatory T cells have been shown to produce the receptor alpha-1-beta-1 integrin (VLA-1) directed against collagen type IV (collagen of the basement membrane). This integrin is expressed on epidermal lymphocytes in lesional (not unaffected) skin. This suggests that epidermal T cells are central effectors in psoriasis. Blockade of VLA-1 significantly inhibits the migration of human VLA-1-expressing T cells. Psoriasis-associated gene variants involve genes affecting T cell activation and functional T cell differentiation, such as: ZAP70, TRAF31P2, TYK2, IL12B, IL3A, IL3B).

Dendritic cells: Dendritic cells (DCs) are outposts of the immune system and represent links between the specific (acquired) and non-specific (innate) immune systems (see below Immunity, innate/acquired). As so-called professional APs, they express both antigen-presenting HLA class II molecules and co-stimulatory molecules. Myeloid DCs are found in increased numbers in the psoriatic lesion. Under PUVA, lesional myeloid DCs decrease.

Chemokines: Infiltrating Th1 lymphocytes interact with various dermal and epidermal cell systems. A number of chemokines, chemokine receptors, integrins and adhesion molecules are involved (CCR5, CXCR3 receptors, E-selectin, LFA-1, ICAM-1, VLA-4, VCAM-1 and others). These promote adhesion of T lymphocytes and neutrophil granulocytes. Furthermore IL-8 and RANTES (see below chemokines), which induce the migration of certain T-lymphocytes.

Inflammatory mediators (see cytokines below): Numerous inflammatory mediators are detected in psoriatic inflammation: TNF-alpha, IL-8, IL-19. Peripheral mononuclear cells show increased titers of TNF-alpha, IL-1beta, IL-6, monocytes produce increased IL-1alpha, IL-1beta, IL-8. Thus, most "psoriatic lymphocytes" express the CCL27 receptor (=CCR10 receptor). It is possible that the CCL27-CR10 axiswill play a role as a therapeutic target in the future.

The detection of these proinflammatory mediators proves that psoriasis should not only be considered as a local inflammation, but as an inflammatory systemic disease, although the interactions between skin/keratinocytes and systemic response are ultimately not yet clear.

Endothelial cells: Angiogenesis factors (e.g., vascular endothelial growth factor = VEGF) are highly elevated in the psoriatic lesion and in serum. They cause vascular proliferation. VEGF is produced by keratinocytes. Activated dermal capillaries express adhesion molecules (ICAM-1, ELAM-1, VCAM-1) that allow CD4+ T lymphocytes to dock to the endothelium and penetrate through the vessel wall. The role of nitric oxide (NO) (INF-gamma is an inducer of NO) vasodilator is still unclear.

Occurrence is possible at any age. Predominantly occurring for the first time in the 2nd to 3rd decade of life (type I), more rarely in the 5th decade of life (type II). Prevalence in <20-year-olds is 0.8%.

No sex preference.

2/3 of psoriatics have mild psoriasis often requiring no treatment. Approximately 80% have nail involvement.

According to age of manifestation and association with HLA alleles, one distinguishes:

• Type I psoriasis (maximum manifestation between 20 and 30 years of age; association with alleles Cw6, B13, B57, DRB1). Association with streptococcal infections detectable.
• Type II psoriasis (manifestation maximum between 50 and 60 years of age; association with HLA alleles Cw2, B27).
• HLA-Cw6-positive psoriatics have a 10-fold increased risk of disease with preferred disease type: Younger age of manifestation, frequently psoriasis guttata type, severe disease course.

For psoriasis arthropathica associations with HLA genes CW6, B13, B17, B27, DR7 are known.

Genetic studies show that type I and type II psoriasis are different diseases.

The mean duration of disease in psoriatics is 21.8 years (1.0-66 years).

Infestation pattern (MAPP study - 3,426 patients): elbows (46%), capillitium (45%), knees (31%), trunk (24%), face (15%), palms (12%), soles (11%), nails (11%), genital area (7%).

Joint symptoms in psoriasis patients with primary skin involvement: knee (45%), fingers (19%), hip (16%), spine (14%), ankle (11%), wrist (8%)

The skin changes of psoriasis manifest themselves most frequently in the chronic stationary form with plaques of varying size, inflammatory redness, sharply demarcated, covered by silvery scales (depending on the pretreatment, these may be completely absent). This form of progression can occur in both type I psoriasis and type II psoriasis.

The acute exanthematic form of progression shows a strong eruption pressure and is preferentially found in type I psoriatics. Frequently, relapses are triggered by infections with beta-hemolytic group A streptococci.

Because of the disease activity (relapse activity) and the resulting therapeutic consequences, it is useful to distinguish between:

• chronic stationary psoriasis vulgaris (chronic stable plaque psoriasis)

and the

• chronicallyactive ps oriasis vulgaris (relapsing psoriasis)

to be distinguished. Diagnostically important is the triggering of different "psoriasis phenomena" within the foci:

• Candle spot phenomenon
• Phenomenon of the last cuticle
• Auspitz sign.

A pathogenetically important phenomenon is the Köbner phenomenon.

Other clinical variants of psoriasis are:

• chronic stationary plaque psoriasis
• psoriasis anularis
• psoriasis capillitii
• erythema anulare-like psoriasis
• Erythrodermia psoriatica (erythrodermic maximum form of psoriasis)
• Psoriasis follicularis
• Psoriasis guttata
• Psoriasis intertriginosa
• Psoriasis inversa
• Pustulosis palmaris et plantaris
• Psoriasis pustulosa palmaris et plantaris
• Psoriasis seborrhoides
• Psoriasis of the nails.

Oral mucosal changes are usually observed only in pustular psoriasis generalisata.

Joint and skeletal involvement (in about 20-30% of pat. with psoriasis) see below.:

• Psoriasis arthropathica
• Arthritis psoriatic (psoriasiarthritis)

The non-pretreated psoriasis papel shows hyper- and vigorous parahyperkeratosis, acanthosis and papillomatosis in typical expression. Elongated narrow rete ridges, which may be bulbous at their lower end; apically bulbous papillary bodies, focal suprapapillary epidermal thinning with absent stratum granulosum; elongated dilated capillary loops; subcorneal or also intracorneal Munro microabscesses.

Diffusely distributed lymphocytic inflammatory infiltrates are found in the upper and middle dermis. Perivascular inflammatory infiltrates consisting of histiocytes, predominantly CD4-positive lymphocytes, and usually a few polymorphonuclear neutrophilic leukocytes are found in the upper and middle dermis sections; there is varying degrees of epidermotropy with only minor signs of spongiosis (DD. eczema reaction).

In the differential diagnosis of psoriasis, the predominant manifestation type plays the decisive role (see below). It is not difficult to diagnose psoriasis vulgaris untreated and in full clinical expression. It becomes more difficult with the clinical variants of the psoriasis family (see below pustular psoriasis, arthropathic psoriasis). Here, completely different clinical pictures will have to be taken into consideration in terms of differential diagnosis (differential diagnosis, see there). The differential diagnosis of psoriasis vulgaris is referred to depending on the subtype (see above).

Patients with severe psoriasis have a reduced life expectancy of about 5 years.

Coronary heart disease: Recent evidence suggests that psoriasis is an independent risk factor for coronary heart disease. Only 40% of psoriatics are free of coronary artery calcifications compared to 72% of the control group with non-psoriatics. Moreover, among psoriatics, the proportion of severe calcifications and stenoses as well as of myocardial infarctions is much higher than in non-psoriatics. An analogous risk spectrum, which is reduced under therapy with TNF-alpha blockers, is also found in patients with rheumatoid arthritis.

Obesity: Significantly increased BMI and increased abdominal and hip circumference in psoriatics.

Metabolic syndrome: Psoriatic patients are more likely to meet criteria for metabolic syndrome (MetS) than the average population; furthermore, there is increased insulin resistance.

Hypertension: Psoriatic patients are at increased risk for hypertension. The use of beta-receptor blockers appears to significantly increase the risk of new onset or exacerbation of psoriasis.

Crohn's disease: Patients with psoriasis are more likely to develop Crohn's disease. An undefined susceptibility locus on chromosome 16q has associations with both psoriasis and Crohn's disease.

Celiac disease: In a larger collective, antibodies against a tissue transglutaminase were detected in 4% of psoriatic patients (non-psoriatic control collective 0.4%). Gluten-free diet also leads to improvement of psoriasis.

Alcohol and smoking are trigger factors for psoriasis.

IgA nephropathy (IgAN): IgA nephropathy appears to be detected more frequently than average in severe psoriasis (Garces CC et al. 2021).

Psoriasis is associated with stigmatization by visible lesions, by itching especially when affecting the intertriginous spaces, with a disturbed self-perception. There is a considerable limitation of physical and mental performance.

There is a negative association with "atopic dermatitis". This occurs 50x less frequently in psoriatic patients.

Main points: Due to the expansion of the drug spectrum, increasingly potent local as well as systemic antipsoriatics have become available to medicine in recent years. The increasing understanding regarding cutaneous immunological processes opens several possibilities of therapeutic intervention. A number of immunosuppressants and immunomodulators are available for this purpose, and others are under development. Based on their mode of action, they can be divided into 5 groups:

• Inhibitors of effector cytokines (especially TNF-alpha)
• Inhibitors of T-cell proliferation
• Inhibitors of T cell activation
• Inhibitors of T cell migration
• Modulators of the immune response
• Inhibitors of keratinocyte proliferation.

However, systemic therapies are often associated with not inconsiderable side effects. Likewise, the treatment costs must be taken into account, which, depending on the therapeutic agent, range between 2,000-30,000 euros per year. In this respect, systemic antipsoriatics should only be used after very careful indication. The therapy must be closely monitored by the treating physician. The physician must be closely familiar with the modalities of action and the side effect profile of the preparations. The duration of treatment must always be questioned.

Therapy combinations: Since clinical studies are almost exclusively evaluated as monotherapies, combination therapies (system therapy+system therapy, system therapy+external therapy; external therapy+external therapy, etc.) are a practical necessity.

Climatic therapy: Stays of several weeks in a sea or mountain climate are often very effective for a few weeks or months, but their effectiveness is limited in time after the end of the stay. Cures, e.g. at the North Sea or Baltic Sea as well as at the Dead Sea (German Medical Center (DMZ) at the Dead Sea in Ein Bokek, Israel or Dead Sea Spa Medical Center in Jordan) have proven to be effective.

Psoriasis and tonsillectomy: Opinions on the success of tonsillectomy are divided. Carriers of the allele HLA-Cw6 are 10 times more likely to be affected by psoriasis. Homocytogy for HLA-Cw6 is associated with a higher risk of disease. At the same time, these patients suffer more frequently from streptococcus-based pharyngitis. Apparently, this particular psoriasis clientele benefits from tonsillectomy.

Upgrade criteria: Not only the pure PASI and DLQI score determine the severity of psoriasis. According to the European consensus, certain factors can lead to a particularly severe reduction in quality of life and require an upgrade in severity (from mild to moderate to severe), thus necessitating systemic therapy. These so-called upgrade criteria are:

• Infestation of visible regions of the body,
• Infestation of larger regions of the scalp,
• Infestation of the genitals,
• Infestation of the palms/soles of the feet,
• Infestation of more than two fingernails,
• Severe itching that prompts scratching,
• Presence of single persistent plaques.

The classic external treatment methods are: dithranol, retinoids, salicylic acid, urea, glucocorticoids, vitamin D3 _analogs, phototherapy (UV therapy), balneo-phototherapy, tacrolimus (strictest indication due to unclear long-term side effects! Off-label use!), pimecrolimus (strictest indication due to unclear long-term side effects! Off-label use!).

Vitamin D3 _analogs:

• Calcipotriol: In 0.005% ointment base (e.g. Daivonex, Psorcutan) well suited for outpatient therapy. Caution! Resorptive NW (hypercalcemia, nephrocalcinosis)! Limit the daily amount to 10 g, the weekly amount to 100 g. Treated skin area < 30% of the KO. Apply 2 times/day, if necessary also under occlusion. Possible irritation in the facial area. Combination with glucocorticoids is possible (e.g. ^Daivobet®; this combination is also available as a spray foam - ^Enstilar®). Newer combination preparations Calcipotriol/betamethasone (^Wynzora®)
• Calcitriol: (Silkis 3 μg/g ointment). Due to the accuracy of fit at the vitamin _D3 receptor, a concentration of 0.0003% is sufficient. Limit the daily amount to 30 g (weekly dose 210 g), treatable skin area 35% KO, application 2 times/day. Also in intertriginous skin areas and with caution on the face.
• Tacalcitol (^Curatoderm®): Application 1 time/day. Treatment of the facial area and possibly the intertriginous areas is possible. In 0.0004% ointment base and emulsion for application once a day, also suitable for sensitive areas. Approved for children from 12 years of age, maximum daily dose 10 g.
• Vitamin D3 _analogs in rotation with dithranol (^Psoradexan®) have proved particularly effective. If necessary in combination with UVB irradiation.

Retinoids:

• Tazarotene: (Zorac 0.05% and 0.1% ^Gel®) 1 time/day. Caution! Irritant effect! Allow preparation to absorb well, do not reapply cream.

Dithranol:

• Inpatient treatment: Classic long-term dithranol therapy (see Table 1) with increasing concentrations (Psoradexan, Psoradexan mite/forte). The dithranol ointment (vaseline-based) is supplemented with 2% salicylic acid for reasons of preservation. Treatment is generally carried out 2 times/day. Start with 0.05% dithranol, increase to 0.1%, 0.25%, 0.5%, 1%, 2% up to max. 3% R076 R074 depending on the skin condition. A rotation principle (see Table 2) with dithranol alternating with medium-strength glucocorticoids such as 0.1% betamethasone cream(e.g. Betagalen, R029 ) or 0.1% triamcinolone cream (e.g. Triamgalen, R074 ) has proved successful.Triamgalen, R259) or a 0.05% calcipotriol ointment (e.g. Daivonex ointment, Psorcutan ointment) or also tacalcitol (Curatoderm), see also interval therapy, tandem therapy. Supplement with balneo-phototherapy: Before ointment therapy in the morning, brine bath in 1% NaCl solution with a bath duration of 25-20 minutes, dry skin briefly and follow with UVB irradiation. Initial dose 1/3 of the individual MED. Increase by the initial dose every 3 days.
• Resistance to therapy: Individual psoriasis plaques (knees, elbows, sacrum region) prove to be very resistant to therapy. In these areas, apply dithranol under an occlusive film such as hydrocolloid film (e.g. Varihesive film) or simple household film, if necessary alternating with glucocorticoid ointments, twice a day for 2 hours.
• Outpatient treatment: Dithranol minute or short-term therapy. Use of dithranol in washable ointment base R074. Alternatively, ready-to-use preparations in different concentrations are available for short-term therapy (e.g. ^Psoradexan® mite/forte, ^Micanol®).

Glucocorticoids:

• Contraindicated as the sole therapeutic principle for extensive psoriasis (risk of systemic side effects due to absorption of the highly potent external glucocorticoids). Initial therapy with glucocorticoid ointments/creams is acceptable for a few, chronically stationary foci. Combinations of external glucocorticoids with salicylic acid have proved successful.
• Mometasone furoate (Ecural Fat ^Cream®), betamethasone valerate (^Betnesol®, ^Betagalen®, R029 ), 0.1% triamcinolone acetonide (Triamgalen, R260 ), amcinonide (^Amciderm® Ointment/Fat Ointment). Caution! Glucocorticoids are not antipsoriatics, they suppress the inflammation for a few days!

Salicylic acid: this keratolytic and antiphlogistic agent is rightly used on the basis of decades of good clinical experience. The study documentation on this form of therapy is inadequate and is unlikely to improve in the coming decades. Nevertheless, the use of a 2-10% application form can be recommended without hesitation.

Calcineurin inhibitors: Topical treatment with calcineurin inhibitors is useful and successful for circumscribed foci. Successes have also been described for tacrolimus and pimecrolimus in psoriasis inversa.

Phosphodiesterase inhibitors: Currently still experimental - 0.3% roflumilast cream; roflumilast is a selective, highly effective inhibitor of phosphodiesterase 4 (PDE4) with approval for bronchial asthma. The efficacy of topical roflumilast was successfully tested in a randomized double-blind study (n=331) in patients with plaque psoriasis (Thurston AW Jr et al. 2023). Further results remain to be seen.

Coal tar: Low effectiveness; lack of compliance due to the inherent odor of the tar preparations! Tar preparations can no longer be recommended today due to potential long-term side effects.

SUP: Favorable effects can be achieved by selective ultraviolet phototherapy (SUP), using UVB rays with an emission maximum at 305 and 325 nm. Especially in combination with dithranol ointments and brine baths, this form of therapy has proven successful in the treatment of chronic stationary psoriasis. Disadvantage: High time expenditure, since usually approx. 30 applications are necessary to achieve a satisfactory result. UVB 311 nm narrow spectrum irradiation is preferable to conventional UVB broad spectrum therapy due to better or at least equal therapeutic efficacy and at the same time less erythema effect. It is recommended to apply 70% of the previously determined MED as the first therapeutic dose.

In moderate psoriasis, UVB irradiation, which can be localized with pinpoint accuracy, is preferable because of the significantly lower UV exposure, e.g. with B-Clear (high equipment purchase costs!).

Balneophototherapy: Several larger studies (evidence level Ib) prove a superiority of brine UVB therapy compared to UVB therapy alone.

Notice. In the implementation of this treatment method, the required brine concentrations between 4.5-12% prove to be practicable only to a limited extent!

In principle, phototherapies can be combined with system therapies. Experience is available for MTX. There are no recognizable contraindications for fumarates. For Ciclosporin A the combination is to be rejected because of the increased carcinogenicity. X-ray pre-irradiated skin areas should be covered during phototherapy.

Photochemotherapy (see PUVA therapy below): Combining PUVA therapy with internal administration of retinoids ( RePUVA therapy = retinoid + PUVA ) may reduce overall radiation exposure.

Balneophotochemotherapy (see PUVA bath therapy below): Here, the external application of methoxsalene is via a full body bath, partial bath or shower application. Due to the higher concentration of the active ingredient of methoxypsalene on the skin surface, a reduction of the applied total UVA dose can be achieved in comparison to systemic PUVA therapy. Treatment scheme, see below. PUVA bath therapy.

Photodynamic therapy: It represents a therapy option, although the data situation cannot be assessed conclusively at present. Similarly, standardized instructions for use have not yet been established.

The indication for systemic therapy of psoriasis must be subject to particularly strict provisos.

• The classical external treatment methods should be sufficiently exhausted.
• Only if no acceptable skin condition can be achieved by the external therapy approaches, a system therapy should take place.

Thus, systemic therapies are reserved for the moderate and severe forms. Classification according to the guidelines. These include chronically active, therapy-resistant, large-area psoriasis vulgaris, pustular psoriasis, psoriatic erythroderma,
all forms of psoriasis arthropathica that cannot be adequately treated monotherapeutically with nonsteroidal anti-inflammatory drugs, severe therapy-resistant psoriasis capitis, and psoriasis palmaris et plantaris.

Prerequisites for the system therapy of psoriasis:

• Psoriasis should be unmanageable or no longer manageable with available local therapeutic agents, resulting in long (more than two months per year) periods of disease with significant distress.
• The efficacy of the systemic therapeutic agent must be proven beyond doubt.
• The systemic therapeutic agent must act rapidly (within four weeks) and produce long-term, clinical freedom from symptoms.
• Even with long-term application (several months) of the drug, there must be no permanent, therapy-induced organ damage that is life-limiting or limits the individual's quality of life beyond that which is primarily disease-related.
• Possible acute side effects must be detectable by standard clinical examination techniques and laboratory parameters and manageable by simple means.
• Therapy must be feasible on an outpatient basis; the therapeutic range should be such that follow-up appointments are not necessary more frequently than every four weeks.

Therapeutic agents in detail:

A) Conventional systemic therapeutics.

• Fumaric acid esters (e.g. ^Skilarence®, ^Fumaderm®): Favorable risk-benefit ratio. Therapy suitable as long-term therapy. Regular laboratory value checks are required. The pharmacological effects of fumaric acid esters are not yet sufficiently known. Probable effects are an antiproliferative effect on lymphocytes and a selective immunomodulatory antipsoriatic effect on activated T lymphocytes. Particularly good effects by FAE are observed in chronic plaque psoriasis. However, localized or generalized exudative psoriasis forms such as pustular psoriasis generalisata or pustular psoriasis palmaris et plantaris also respond well to fumarates. Good effects are also observed in psoriasis capitis. Significant improvements of psoriatic nail involvement have been reported in several studies, 30-40% of cases are improved under therapy with FAE. Treatment starts in the 1st week of therapy with 1 tbl. Fumaderm initial, is increased by 1 tbl. in the 2nd week; then transition to 1 tbl. Fumaderm; further weekly increase by 1 tbl./day Fumaderm. Max. Dosage depending on clinical effect 6 tbl. Fumaderm/day. Maintenance dose is between 1 and 6 tbl. of Fumaderm. Side effects are primarily flush symptoms (1/2 hour to 6 hours after ingestion); flush symptoms persist for minutes to half an hour. With increasing duration of therapy, there is a marked decrease in flush symptoms. Gastrointestinal problems such as nausea, diarrhea, stomach cramps may occur. These symptoms also remit with therapy; mild to marked lymphopenias are regular side effects of therapy; eosinophilia is less common. Dose adjustment should be made in the presence of leukopenia, decrease in lymphocyte count < 500/µl, persistent eosinophilia > 25%, increase in creatinine > 30%, or massive tubular proteinuria. Combinations with other systemic antipsoriatics such as MTX or ciclosporin or retinoids are not currently recommended due to lack of experience. Laboratory testing with blood counts, monitoring of liver and kidney function, and urinalysis is required on a 4-weekly basis. Although teratogenicity has not been established, FAEs should not be given during pregnancy.
• Acitretin (^Neotigason®): Vitamin A derivative used in Europe in psoriasis therapy as a systemic therapeutic. The best effects are found in pustular psoriasis or erythrodermic forms. Acitretin causes rapid loss of psoriatic scaling. Clinical freedom from manifestations is achieved in psoriasis vulgaris in nearly 25% of patients. Dosage: Initial 0.5-1.0 mg/kg bw; as a maintenance dose, 0.1 (max. 0.2) mg/kg bw should not be exceeded. Acitretin is characterized by high lipophilicity, resulting in accumulation of the drug in adipose tissue during long-term therapy. The very delayed release of acitretin after discontinuation of the preparation results in a half-life of 80-100 days. This has significant consequences with regard to the known teratogenicity of the preparation and considerably reduces the possibilities of using the preparation in women of childbearing age (contraception up to 2 years after discontinuation of the preparation). Acitretin can be used in combination with radiation therapies (ReSUP; RePUVA).
• Ciclosporin A: High response rate. Nephrotoxicity and possible carcinogenicity in long-term therapy are known NW. Ciclosporin A (Cy A) represents a rapidly effective systemic treatment strategy. Clinical success occurs within days to a few weeks. Ciclosporin is particularly effective in severe therapy-resistant psoriasis arthropathica. However, generalized plaque psoriasis, pustular forms and psoriatic erythroderma also respond to ciclosporin. Dosage: 2.5 - max. 7.5 mg/kg bw p.o. Regular laboratory controls, especially of blood, liver, and kidney status, are required.
• Glucocorticoids: Can be used only for a very short time in case of high relapsing activity of psoriasis. Glucocorticoids should be rejected as systemic long-term antipsoriatics. Their use generally leads to prompt clinical effects. In this respect, they can be used in a medium-high dosage (100-150 mg prednisolone) in highly exudative forms of psoriasis (e.g., in an acute episode of pustular psoriasis) in the short term (2-3 days). Regardless of the negative evaluation of systemic glucocorticoids, they are prescribed by internists and general practitioners most frequently of all systemic therapeutics (!).
• Methotrexate (MTX): Indication is especially psoriasis arthropathica. MTX has a proven clinical effect in moderate and severe psoriasis vulgaris. MTX is suitable for this indication according to the German and European S3 guidelines. MTX can also be used, if necessary, in combination with etanercept - adalimumab or fumarates in severe exudative forms of psoriasis such as Zumbusch-type pustular psoriasis. In the pustular forms of psoriasis, the MTX effect is explained by the proven inhibitory effect of MTX on the neutrophilic leukocytes of the psoriatic patient. Dosage: Test dose: To determine hematological hypersensitivity, initial application of 2.5 mg p.o. or i.m.; check blood count after 5-7 days; if neutroph. Leukocytes below normal value: discontinue therapy. Acute toxicity is rare (elderly with impaired renal function). If leukocytes drop critically below average methotrexate dose, give leucovorin immediately (3.0-6.0 mg folinic acid = 1 or 2 amps leucovorin i.v. or i.m.). Then administer the same dose again 4 times at 3-6 hourly intervals. Long-term application causes liver damage in approximately 33% of patients. Liver fibrosis is observed in a maximum of 10% and liver cirrhosis in 5% of patients. Regular monitoring of blood, liver and kidney values (fortnightly) is necessary. Similarly, biannual sonographic liver examinations are recommended. If gastrointestinal side effects should occur, the intracutaneous form of application is recommended. A comparison of MTX and fumarates in severe plaque psoriasis (baseline PASI between 14 and 18) showed equivalence in the treatment groups.
• Apremilast (Otezla®), an oral thalidomide analog (phosphodiesterase-4 inhibitor) developed for the indications spondylitis, psoriatic arthritis or psoriasis arthropathica, and psoriasis vulgaris by Celegene. In the phase III study (ESTEEM), patients with moderate to severe psoriasis were treated with 30mg 2x/day apremilast for 52 weeks. At week 16, 28.8% of those treated achieved a PASI-75 response (5.8% on placebo).

B) Biologics with approvals for psoriasis therapy.

Monoclonal antibodies

• TNF-α inhibitors

  • Etanercept (^Enbrel®): Fusion protein (dimeric protein) of human tumor necrosis factor receptor and human IgG1 that specifically binds to TNF-α, biologically inactivating it and thus preventing the interaction of the molecule with its membrane receptor. The preparation Enbrel is approved for the treatment of plaque-type psoriasis vulgaris in children (from the age of 6) and adolescents as well as in adults. The effect of the preparation usually occurs after the first injection. Should not be prescribed during pregnancy and lactation (insufficient data). Dosage (Pat. > 5 y.): 2 times/week 25 mg s.c. Alternative: 2 times/week 50 mg s.c. for up to 12 weeks, then 2 times/week 25 mg s.c. Treatment until remission, for a maximum of 24 weeks in total. Discontinuation of therapy in patients who have not responded after 12 weeks. Intermittent therapy approaches do not lead to treatment resistance. Note: Approved for children > 5 years of age in severe juvenile plaque psoriasis. Combination of etanercept with retinoids has been described as successful. So has the combination with MTX. Note: an etanercept biosimilar (Erelzi®) is approved for rheumatologic and dermatologic indications (so in plaque psoriasis) and is equally effective and safe.

  • Adalimumab (^Humira®): The drug neutralizes the biological functions of TNF-alpha by highly specific binding to TNF-alpha molecules and inhibition of interaction with cellular p55 and p75 TNF receptors. Secondary inhibition of IL-1 and IL-6 production and secretion, as well as leukocyte migration and expression of adhesion molecules. Combination with low-dose MTX is recommended to avoid formation of autoantibodies to adalimumab. Can also be used as monotherapy if MTX is intolerant. Dosage: adults/adolescents > 18 yrs: 1 time/14 days 40 mg s.c. Recent studies indicate that not only arthritis but also skin symptoms can be improved by adalimumab. Adalimumab now has EU approval as first-line therapy.
  • Infliximab (^Remicade®): Chimeric monoclonal antibody (mouse-human) that interrupts the pro-inflammatory signal transduction chain by binding TNF-α. Approved for the treatment of rheumatoid arthritis and Crohn's disease, psoriasis vulgaris and psoriasis arthropathica. Dosage: 5 mg/kg bw i.v. over approximately 2 hours. Good, rapid results already after a single application with disease-free intervals of up to 3-4 months. In case of recurrence, a new treatment cycle should be performed within 14 weeks to minimize the risk of hypersensitivity reactions (sensitization to chimeric antibodies). Although described only in rare cases, emergency precautions (presence of a physician during application, epinephrine, corticosteroids, and antihistamines) should be taken to treat possible anaphylactoid incidents. Exclusion of active tuberculosis must be performed. TB screening with quantiferon TB gold test and chest X-ray (not older than 6 months) are recommended.
  • Certolizumab pegol (^Cimzia® ): Certolizumab pegol is a pegylated monoclonal antibody from the drug class of TNF-alpha blockers. Pegylation means that polyethylene glycol (PEG) moieties are incorporated into the antibody. This can extend the half-life of the drug. The absence of the Fc IgG moiety in this monoclonal antibody is considered an advantage in that some potential side effects of monoclonal antibodies are thought to be related to the Fc moiety. At the same time, the pegylation changes the so-called pharmacokinetics of the antibody, i.e. the behavior of the drug in the organism. Certolizumab is approved for the treatment of moderate to severe plaque psoriasis. Therapy with certolizumab pegol is administered as a subcutaneous injection (s.c.). In the therapy of rheumatoid arthritis, the usual dose is 200 mg certolizumab/14 days. In the initial phase of therapy, the dose is doubled, i.e., 400 mg is administered on the first day, as well as after 14 and after 28 days.
• Interleukin-12 (IL-12) and -23 (IL-23) antibodies:
  • Ustekinumab (^Stelara®): Human monoclonal antibody directed against the p40 subunits of the cytokines interleukin-12 (IL-12) and -23 (IL-23). Moderates Th1 lymphocyte differentiation, as well as the IL-23/IL-17A axis of the TH17 immune response. Approved for the treatment of moderate-to-severe plaque psoriasis in adults who have had no or inadequate response to other basic therapies (e.g., MTX, ciclosporin A, fumarates, PUVA therapy) or who have contraindications or intolerances. Dosage: 45 mg s.c. at the start of therapy and after 4 weeks. Maintenance dose: 45 mg s.c. every 12 weeks. Compared to etanercept, ustekinumab shows the highest 5-year efficacy (Zweegers J et al. 2017).
• IL-17 antibody:
  • Brodalumab (^Kyntheum® - Approval 09.2017 ): Recombinant, fully human, monoclonal immunoglobulin IgG2 antibody. The antibody binds with high affinity to human IL-17RA (interleukin-17 receptor), inhibiting the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17F, IL-17A / F heterodimer and IL-25, resulting in broad inhibition of psoriatic inflammation. Indication: Moderate to severe plaque psoriasis (psoriasis vulgaris). Approved in the EU directly for first-line therapy. Approved in the US under the name Siliq® as second-line therapy only.
  • Secukinumab (^Cosentyx®): the anti-Il-17A antibody Secukinumab (Cosentyx®), a monoclonal antibody introduced with the FEATURE and JUCTURE studies, each with convincing clinical results. Dosage: 150/300 mg s.c. every 4 weeks. Secukinumab was approved by the European Medicines Agency (EMA) in January 2015 for primary systemic therapy of moderate-to-severe plaque psoriasis in adult patients requiring systemic treatment. A 5-year control study demonstrated an unchanged high response rate to the drug. In 2016, the indication was expanded to include psoriatic arthritis and ankylosing spondylitis.
  • Ixekizumab (^Taltz®) is another monoclonal antibody approved for psoriasis that binds with high affinity and specificity to the pro-inflammatory cytokine interleukin-17A (IL-17A) and neutralizes it. The substance is applied as a subcutaneous injection. The initial dose is 80 mg twice. Thereafter, ixekizumab is administered every two weeks.
• Anti-Il-23 antibody
  • Guselkumab (^Tremfya®), a monoclonal antibody that demonstrated superiority over adalimumab in moderate-to-severe psoriasis in the VOYAGE-1 trial. Guselkumab has been available since November 2017 as first-line therapy in adult patients with moderate-to-severe plaque psoriasis. The human monoclonal antibody selectively targets the "master cytokine" interleukin-23 (IL-23). This cytokine plays an important role in the inflammatory process of psoriasis: The cytokine activates a specific subpopulation of T-cells, TH1 and TH17, which trigger TNF-α-mediated inflammation in psoriasis.

  • Tildrakizumab (^Ilumetri®)is a humanized IgG1/k monoclonal antibody (produced in Chinese hamster ovary cells- CHO cells-) with anti-inflammatory and selective immunosuppressive activity. Tildrakizumab is used for the treatment of plaque psoriasis. The effects are based on the binding and inactivation of the cytokine interleukin-23 (IL-23).

  • Risankizumab (Skyrizi®⁾: is a humanized IgG1/k monoclonal antibody (produced in Chinese hamster ovary cells -CHO cells-) with anti-inflammatory and selective immunosuppressive effects. Risankizumab is used for the treatment of plaque psoriasis. The effects are based on the binding and inactivation of the cytokine interleukin-23 (IL-23). The response to risankizumab was significantly better compared to ustekinumab. The co-primary endpoint, appearance-free or nearly appearance-free skin, was achieved by 84% and 88% of patients, respectively, after 16 -weeks of therapy.

Approved preparations for psoriatic arthritis:

• Etanercept (Enbrel®⁾: Approved for juvenile idiopathic arthritis at 4 years of age and older.
• Infliximab (^Remicade®): See above.
• Leflunomide (Arava®⁾: The active metabolite inhibits, among other things, dihydroorate dehydrogenase, a key enzyme in pyrimidine and thus nucleic acid biosynthesis, including in the de novo synthesis of activated lymphocytes. Leflunomide prevents the de novo synthesis of pyrimidine and thus blocks the proliferation of activated lymphocytes. Thus, over time, there are not enough activated lymphocytes available to sustain the chronic inflammatory process. Results of clinical studies suggest that leflunomide shows good efficacy in patients with psoriatic arthritis and in seronegative spondyloarthritides. However, no larger, systematic studies are yet available on this topic. Dosage: Saturation of the level: 1 tbl. (100 mg) p.o. 1 time/day. From day 4: 1 tablet daily with only 20 (10) mg p.o. The reduced dose of 10 mg daily is recommended when intolerance occurs with the higher dose of 20 mg daily. However, lower efficacy also occurs in these cases. Clinical effect occurs on average after 14 days. About 75% of patients benefit after 1-2 months. Side effects include GI discomfort, headache, hepatotoxicity, and exanthema.
• Golimumab (Simponi®⁾ 1 time/month 50 mg s.c. (same day of each month), in combination with the individually required dose of MTX if necessary.
• Adalimumab (Humira®⁾: See above.

• Janus kinase inhibitors: Tofacitinib is already approved for psoriatic arthritis.

Drugs not (or not yet) approved with known efficacy in psoriasis and/or psoriatic arthritis (off-label use):

• Alefacept (Amevive®): Immunosuppressive fusion protein (dimer) consisting of a CD2 extracellular binding site of leukocyte functional antigen 3 (LFA-3) and portions of IgG1. Effects: Inhibition of lymphocyte activation by specific binding to CD2 and inhibition of LFA-3/CD2 interaction. Indication: In moderate and severe forms of psoriasis vulgaris requiring systemic treatment. Dosage: 1 time/week 7.5 mg alefacept i.v. or 1 time/week 15 mg i.m. for 12 weeks. If necessary, repeat therapy cycle after a 12-week break in therapy. Contraindication: lymphocytopenia at planned start of therapy. Weekly monitoring of lymphocyte subpopulations, especially CD4 lymphocytes in differential blood counts!k
• Tacrolimus (Prograf®): Active ingredient from the group of immunomodulating macrolactams. Tacrolimus inhibits initial T-cell activation, differentiation and proliferation of cytotoxic T-cells and specifically the expression of E-selectin (adhesion molecule on endothelial cells). Indication: Severe forms of psoriasis vulgaris and osteoarthropathia psoriatica. Dosage: 0.1-0.2 mg/day/kg bw p.o. divided into 2 single doses. Ventricular wall and septum may thicken during immunosuppression with tacrolimus; therefore, regular echocardiographic examinations are required.
• Mycophenolate mofetil (CellCept®): Immunosuppressant, ester of mycophenolic acid. Antiproliferative effect on lymphocytes and immunosuppressive effect by inhibition of inosine monophosphate dehydrogenase. The effect on cytokine production is still unclear. Indication: In clinical trials for the treatment of severe courses of psoriasis vulgaris and psoriasis arthropathica. Dosage: Psoriasis: Initially 2 times/day 1 g p.o. for 3 weeks, then 2 times/day 0.5 g p.o. for 3 weeks. Psoriasis arthropathica: combination with low-dose acitretin (0.1-0.2 mg/kg bw/day) p.o..

Treatment of psoriasis vulgaris in childhood and adolescence (see below Psoriasis in childhood).

Chronic recurrent course with varying lengths of non-appearance intervals.

Order therapy: avoidance of trigger mechanisms, especially friction, infections, stressors. Also some medications such as beta-blockers, which can lead to psoriasis flares, should be considered here.

Climatic therapy and hydrotherapy: brine baths, baths with dead sea salt which can also be carried out at home, also showers with sea salt shower bath (e.g. Sebamed Meersalz ^Dusche®) have proved successful. In addition to natural tanning, UV therapy with medium-wave UV-B is recommended.

Phytotherapy external s. a. under Psoriasis vulgaris chronic stationary plaque type

Phytotherapeutically, extracts of Mahonia aquifolium (commercially available as a ready-to-use preparation: Rubisan ^® cream or ointment) (s.a. Mahoniae cortex and Mahoniae radix, s.a. Berberin) have proven effective. In a double-blind placebo-controlled study, a significant improvement of psoriatic symptoms was obtained. Especially in intertriginous problem areas (e.g. anal fold, groin) this preparation is quite well tolerated (Bernstein S et al. 2006) .

A smaller double-blind study proved the success of Olibanum indicum with local application (Togni S et al. 2014).

In case of concurrent psoriatic arthritis, see under arthritis psoriatic .

According to current studies, Aloe vera also leads to the healing of psoriatic plaques, due to its anti-inflammatory, antiseptic and antiproliferative properties, see also Aloin.

Betulin contained in the birch round, is also used for its anti-inflammatory, wound healing promoting differentiation, antibacterial, antiviral, antitumor, antioxidant and antipruritic effects. Commercial preparation: ^Imlan®

Witch hazel has proven particularly effective in inverse psoriasis with weeping foci in the anal area and intertrigines.

Frankincense, internally proven in psoriatic arthritis, also showed a significant improvement in symptoms as a cream in a study.

Patients with psoriasis experience a comparable impairment of the psychological and mental components of their health-related quality of life (HRQL = health-related quality of life) as patients with malignancies, arthritis, hypertension, heart disease, diabetes mellitus and depression.

The success of diets is not proven.

The average case costs (outpatients and inpatients) are defined for psoriatic patients by the severity of the case. They fluctuate between 6,700 Euro and 53,000 Euro/year. Inpatients incur costs of 2,300 to 32,000 euros, outpatients incur total costs of 204 to 770 euros. The indirect costs range between 1,300 and 8,200 euro per patient.

The term "psoriasis vulgaris" is used in different ways. It is often used synonymously for the most common form of psoriasis, the "plaque type".

Psoriasis vulgaris and organ transplantation:

The 32-year-old female patient has had severe psoriasis vulgaris with generalized integumentary involvement since the age of 20. In 2006, an allogeneic pancreas and kidney transplant was performed due to Goodpasture syndrome with pulmonary and renal involvement. The subsequent immunosuppressive therapy consisted of prednisone 7.5 mg/day, tacrolimus 8.5 mg/day and mycophenolate mofetil 1.0 g/day.

Psoriasis therapy: The psoriasis therapies carried out before the organ transplantation (OTX) included the usual topical therapy approaches with glucocorticoids, dithranol in different concentration levels, bathing PUVA, UVB irradiation in the first few years. Later, due to insufficient response to local therapy, systemic therapy with fumaric acid esters (FAE) in the usual doses. The FAEs had to be discontinued after a few weeks due to intolerable gastrointestinal problems. 2 years after OTX, there was a permanent and therapy-resistant significant worsening of the skin condition with a PASI of >25 despite adequate topical therapy.

New therapeutic approach: As there were no more sufficient local therapy options available, a therapy with etanercept 2 x 25 mg/week was initiated. This resulted in a continuous improvement of the skin condition. After 10 months of etanercept therapy, the patient was largely appearance-free. No relevant side effects of the therapy had to be observed under this therapy modality. Laboratory: The graft functions were stable. A new tuberculosis screen(quantiferon test; chest X-ray) was negative. Comment: Psoriasis therapy in OTX represents a particular challenge, especially as limited therapeutic options (e.g. phototherapy, side effects of antipsoriatic drugs that can impair graft function), interaction of drugs and psoriasis activity are to be expected (e.g. due to the alternating administration of steroids). Biologics such as etanercept (or adalimumab) represent an effective and tolerable treatment option for OTX patients with severe psoriasis, as far as can be assessed on the basis of the limited experience currently available.

Psoriasis and semaglutide:

Since psoriasis is often associated with abdominal obesity and type 2 diabetes (T2D), an -observation of psoriasis under therapy with semaglutide offered itself. Attenuation of epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) for each coronary artery, defined as mean attenuation expressed in Hounsfield units (HU), was assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was -80 HU and PCAT attenuation of the right coronary artery (RCA) was -68 HU, values associated with increased cardiac mortality risk. The Psoriasis Area and Severity Index (PASI) was 12.0, indicating severe psoriasis, while the Dermatology Life Quality Index (DLQI) was 20, indicating a negative impact on the patient's life. Treatment with semaglutide was initiated (starting at 0.25 mg/week for 4 weeks, then increasing to 0.50 mg/week for 16 weeks and then to 1 mg/week). After 10 months, treatment with semaglutide normalized glycated hemoglobin and led to weight loss, particularly in the abdominal region, followed by a reduction in EAT volume as measured by computed tomography. PASI and DLQI decreased by 98.3% and 95%, respectively, indicating a significant improvement in psoriatic skin lesions and a marked improvement in the patient's quality of life compared to baseline (Malavazos AE et al. 2023).

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