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Facing psoriasis and atopic dermatitis: are there more similarities or more differences?

European Journal of Dermatology. Volume 18, Number 2, 172-80, march-april 2008, Clinical report

DOI : 10.1684/ejd.2008.0357

Summary

Author(s) : Dagmar Wilsmann-Theis, Tobias Hagemann, Julia Jordan, Thomas Bieber, Natalija Novak , Department of Dermatology and Allergy, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

Summary : Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases. It has been assumed for a long time that these diseases have a completely different background. Recent findings about the genetic, epidemiologic and pathophysiologic factors of both diseases have remarkably improved our knowledge about the complex mechanisms underlying AD and Pso. Beyond that, in view of these findings, the question arises, which similarities and differences between AD and Pso exist. In order to address this point, we provide an overview about the current knowledge in the field of AD and Pso.

Keywords : atopic dermatitis, genetics, pathophysiology, psoriasis

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ARTICLE

Auteur(s) : Dagmar Wilsmann-Theis, Tobias Hagemann, Julia Jordan, Thomas Bieber, Natalija Novak

Department of Dermatology and Allergy, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany

accepté le 12 Novembre 2007

Atopic dermatitis (AD) and psoriasis vulgaris (Pso) are the most frequent chronic relapsing skin diseases. It has been assumed for a long time that AD is pathologically completely different from Pso. However, in recent years, evidence has arisen that a high number of similarities exist between the two diseases. It is well known that genetic background and environmental factors have a high impact on both skin diseases. Loci on chromosome 1q21, 17q25, 20p as well as 3q21, which have been identified by linkage analysis with the help of full genome screens as candidate genes for AD, correspond closely with known gene loci for Pso. This supports the idea that AD and Pso might have a couple of shared genes which modulate general cutaneous inflammatory mechanisms and alterations at the level of the epidermal differentiation complex. Although the clinical features of both diseases are quite different, chronic AD lesions and psoriatic lesions share some important immunological aspects. Both are characterized by: T-cell-dominated dermal infiltrates, a similar pattern of pro-inflammatory cytokines in the chronic phase, an impairment by common trigger factors and a good responsiveness to T-cell directed agents as treatment regimes. This article provides an overview of our current knowledge about differences and similarities of AD and Pso facing genetic, clinical, pathophysiological and therapeutical features.

Definition and epidemiology

Pso is a chronic inflammatory disease of the skin and the joints that affects approximately 2% of the population in the world. The incidence varies depending on ethnic groups as well as geographical regions. Interestingly, no significant changes in annual incidence rates of Pso have been reported in the last decades [1, 2].

AD is a major public health problem worldwide with a lifetime prevalence of 10-20% in children and a prevalence of 1-3% in adults. In about 50% of cases AD starts in childhood. The disease improves during adolescence but in one-third of cases it persists with a chronic relapsing course until adulthood. The prevalence of AD has increased by two- to three-fold during the past three decades in industrial countries, but remains much lower in agricultural regions [3-5].

Genetic background

Pso has a familial basis in approximately one third of cases. No simple Mendelian pattern of dominant or recessive inheritance has been observed. First degree relatives of patients with juvenile onset of Pso have a 10-fold-higher risk of developing the disease compared to the general population [6].

Multiple twin and family analyses strongly imply a genetic basis for AD, too. This statement is underlined by the finding that a positive parental history represents one of the strongest risk factors for AD. The incidence rate is doubled if AD is present in one parent and tripled if both parents are affected. However, AD phenotypes do not follow any Mendelian inheritance pattern. AD and Pso are both paradigmatic genetic complex (multifactorial) diseases [7-9].

Genome wide screens carried out in families of German, French, Scandinavian and British children with AD found linkage to gene regions on chromosomes 3q21, 1q21, 11p14, 17q25 and 20p [10-13]. In these studies linkage of total serum IgE to regions on chromosome 3q21, 5q31 and 16q has been found. Surprisingly some of these regions (1q21, 17q25 and 20p) correspond very closely to known Pso loci [12], indicating that AD and Pso are both influenced by gene regions which might have general effects on skin inflammation and dysfunctions in the epidermal differentiation complex (EDC) [14]. Further on, variants in an epidermal collagen gene have been shown to be associated with AD and might contribute to the breakdown of the integrity of the epidermal skin barrier in AD [15]. In contrast, recent findings demonstrate that loss-of-function variants of FLG, the gene encoding filaggrin, which is located in the EDC of the shared chromosome 1q21, do not play a major role in the etiology of Pso, whereas they are strongly associated with AD [16-18]. Moreover further results suggest that some of these psoriasis candidate genes do not account for the previously observed linkage of the 17q25 locus with AD [19].

In addition, chromosome region 16q12, encoding the Caspase recruitment domain containing protein 15, has been reported to be a candidate gene region for both Pso and AD. We summarize these findings in figure 1 and table 1 [7, 9, 20]. As a consequence, further studies are needed to identify disease-causing variants of susceptibility loci/genes in Pso and AD.
Table 1 Published candidate genes for AD and Pso

Chromo-somal location	Gene name		Phenotype	Reference
1q21	PSORS4	IVL (Involucrin) SHC1 (Src homology 2 domain-containing) EDC (Epidermal differentiation complex)	PSO Childhood AD	[7-9] [14, 26, 83-89]
1p35-34	PSORS7		PSO	[7]
2p	PSORS4		PSO	[7, 83]
2q33		CTLA4 (Cytotoxic T lymphocyte-associated 4 receptor)	Early onset AD	[92]
3q21	PSORS5		AD, PSO	[7-9, 26]
3p24.2-21.3		TLR9 (Toll-like-receptor 9)	allergic asthma non-atopic eczema	[8, 9, 26, 31]
4q13	PSORS5	IL8 (Interleukin 8)	PSO	[7, 83, 84]
4q21	PSORS5		PSO	[7, 83]
4q31-34	PSORS9		PSO	[90, 91]
4q32		TLR2 (Toll-like receptor 2)	severe AD	[89]
4q34	PSORS3	IRF2 (Interferon regulatory factor 2)	PSO AD	[7-9, 26, 83, 84, 89-91]
4q35.1
5q31		IL 4 (Interleukin 4)	Extrinisic/ intrinsic AD	[26, 89]
CSF2 (Colony-stimulating factor 2)	AD/ AD at 12 &24months	[89]
IL13 (Interleukin 13)	AD	[26, 89]
IL5 (Interleukin 5)	Blood eosinophilia in AD	[89]
CD14 (Monocyte differentiation antigen CD14)	AD	[89]
5q23-35		IL 4 Cytokine gene cluster	AD	[9]
5q31-33		IL12B (Interleukin 12B)	AD	[89]
SPINK 5 (Serine protease inhibitor, Kalzaltype 5)	AD	[8, 92]
6p21	PSORS1	MHC class II /TNF (Tumor necrosis factor)-alpha, HLA; CDSN (Cornedesmosin); HCR RAN (Ras-like protein Tc4)	PSO (gutatta, arthritis) allergic asthma/ spec. IgE	[7-9, 26, 83, 84, 90, 91]
6q	PSORS1		PSO	[7, 83]
7	PSORS1		PSO	[7]
7p14-15		CARD 4 (Caspase recruitment domain containing protein 4)	AD	[31]
8q24	PSORS1		PSO	[7, 83]
10q22-23	PSORS1		PSO	[7, 83]
11p13	PSORS1		PSO	[7, 83]
11q13		FCER1B (High affinity IgE receptor β chain)	AD	[26, 89]
GSTP1 (Glutathione S-transferase, P1)	AD	[71]
13q14		PHF 11 (Plant homeodomain Zink finger 11 protein)	childhood AD	[8, 9, 26]
14q11.2		CMA1 (Mast cell chymase)	AD	[9, 92, 26, 89]
14q31-32	PSORS1		PSO	[7, 83]
15q	PSORS1		PSO	[7]
16q12	PSORS8	CARD 15 (Caspase recruitment domain containing protein 15)	AD, PSO (Pso arthritis)	[7-9, 8, 91]
16q24.1		Unknown	atopy (allergic asthma)	[7, 26]
16p12		IL4RA (Interleukin 4 receptor alpha chain)	AD	[20, 84, 89]
17q11-12		RANTES (regulated upon activation normally T-cell expressed + secreted	AD	[20, 26, 89]
17q21		EOTAXIN (Eotaxin)	IgE levels in AD	[89]
17q25	PSORS2	SLC9A3R1/NAT9 (solute carrier family 9, isoform 3 regulating factor 1/N acetyltransferase family 9) RUNX1 (runt-related transcription factor 1) Rapamycin (TOR)	childhood AD, PSO	[7-9, 83, 84]
19p13	PSORS6	JUN-proteins	PSO	[87]
19q13.1		TGFB1 (Transforming growth factor β1)	AD	[7, 89]
19q13.3	PSORS2	SCCE (Stratum corneum chymotryptic enzyme)	AD, PSO	[9, 31, 89]
20p	PSORS2		childhood AD, PSO	[7-9, 83]

Clinical aspects

Clinical manifestations and overlapping phenotypes

Skin lesions of Pso consist of chronic, sharply demarcated, dull-red, scaly plaques, which are located primarily on the extensor prominences (i.e. elbows and knees) and the scalp. Nail lesions appear as pits, onycholysis or onychodystrophy. Nevertheless, the disease is enormously variable in its duration and extent and morphological variants are common [2]. The severity of Pso ranges from a limited number of mild lesions to complete body surface involvement [21].

A clinically useful set of criteria for the diagnosis of AD are: atopy; pruritus; eczema and altered vascular reactivity. Acute lesions may initially present with pruritic, erythematous macules or papules. After scratching primary lesions, secondary lesions may appear as excoriated papules with crust and serum exudates. The diagnosis of AD is usually based on clinical criteria. The UK refinements of Hanifin and Rajka’s diagnostic criteria appear to be valid for adults and children of Caucasian and other ethnic groups [22, 23].

Although AD is clinically quite distinct from Pso, some features are shared by both diseases, including dry scaly skin and erythema. The common variant of Pso shows lesions on the extensor prominences whereas AD is located on the flexural parts (figures 3I and J). However, some Pso patients have eczematous skin lesions without the typical thick plaques associated with Pso. The histology of those patients shows features of Pso. Therefore these cases might represent a kind of “eczematous” variant of Pso. Interestingly, patients affected by this variant of Pso often complain about itch, although this is not a typical symptom of psoriasis (figure 3A, 3G, 3H).

Association of AD with high IGE serum levels and sensitization

While the first manifestation of Pso may occur at any age, epidemiological studies have shown that Pso can be divided into two subforms, namely type I and type II Pso. Type I is characterized by an early age of onset with a first manifestation before the age of 40, increased family frequency and a higher association with specific Human-Leucocyte-antigen (HLA) genes, whereas type II Pso starts after the age of 40 without any association with HLA-molecules, without a positive family history for Pso [24].

For AD, also two subforms have been delineated: an extrinsic form which is associated with IgE-mediated sensitization and elevated IgE serum levels involving 70-80% of adult patients and an intrinsic form (now called eczema) without IgE-mediated sensitization and with normal IgE serum levels, involving about 20% of the adult patients [25].

Associated diseases and the role of autoimmunity

The association of arthritis and Pso is one of the best examples of a disease association in dermatology. A strong association between Pso and diseases like Crohn’s disease or ulcerative colitis as well as ankylosing spondylitis has been referred. Further epidemiological studies have revealed that another group of diseases is quite frequently associated with Pso, e.g. diabetes, adiposity, heart failure and hypertension [24].

Pso is considered as a T-lymphocyte mediated autoimmune disease, in which bacterial proteins with similarity to structural proteins of keratinocytes represent potential target antigens. As in autoimmune diseases, pro-inflammatory cytokines arising from complex interaction between the adaptive immune system and components of the innate immune system initiate local inflammation in the skin, the circulation and most likely also in the lymph nodes.

A variety of autoantibodies has been observed in Pso, including antinuclear antibodies, antibodies to small nuclear and cytoplasmic ribonucleoproteins and antibodies to epidermal cells [26]. But until now, no one has ever shown any pathogenic role for these autoantibodies.

Recent investigations have also shown a linkage between AD and autoimmune mechanisms. Moreover it has been shown that patients suffering from AD exhibit IgE autoreactivity to human proteins. These autoantigens are expressed in a variety of cell and tissue types and it is hypothesized that this IgE autoreactivity might represent a kind of endogenous trigger of AD [27, 28]. Other diseases which occur frequently with AD are alopecia areata, hyperhidrosis, ichthyosis vulgaris and pityriasis simplex. A coincidence of AD with patients with Down-syndrome has also been reported [29]. Taken together, beside the association of both AD and Pso with allergic diseases, the diseases associated frequently with AD and Pso are rather different.

Pathophysiology

Trigger factors

Besides putative shared genetic factors, environmental trigger factors, including infections, stress, trauma, smoking (especially in psoriasis/eczema palmoplantaris), and alcohol play a role in both diseases. Pso is a paradigmatic skin disease in which various types of trauma may elicit the disease in previously uninvolved skin. This reaction, known as the Köbner phenomenon, usually occurs about 7-14 days after mechanical damage. Medications like β-blockers, lithium, and interferon-α are known to be provocation factors of Pso [30]. Cessation of oral corticosteroid therapy can also trigger a severe flare or even progression to generalized pustular Pso.

In contrast to Pso, in AD, foods or inhalants (e.g. dust mites, pollen and animal dander) are important allergic triggers. The itch-scratch circle seems to be an important component in the pathophysiology of AD [31]. Therefore, eliminating trigger factors and control of pruritus are pivotal goals in the management of AD [4, 32].

The perception of patients that psychological stress can worsen Pso and AD has been confirmed in clinical studies. Patients may be tempted to reduce stress by abusing drugs or alcohol-activities that can actually increase stress. A stress-depression, stress-aggression or stress-obsession pattern may be accompanied by increased pruritus. The pathophysiology of itch in AD and the pathophysiological interaction of stress in AD and Pso is still not fully understood. Indeed neuropeptides may be of substantial importance for itch sensation and the influence of stress on the disease, since activation of the cortical centres by stress leads to an increased secretion of neuropeptides, such as substance P, from the adrenal glands. Increased levels of substance P, neurokinin A, calcitonin gene related peptide and vasoactive intestinal peptide are found in the skin affected by AD as well as in the skin affected by Pso and might mirror a common link between stress and the exacerbation and impairment of Pso and AD [30, 32-35].

The role of microbes

Bacteria play an important role in the induction of flare ups and maintenance of inflammatory skin disease such as Pso or AD. Toxins from bacteria including Streptococcus and Staphylococcus aureus have been shown to act as superantigens [36, 36-38]. These are microbial proteins which activate a large number of T cells and stimulate the production of powerful pro-inflammatory mediators. For instance, guttate psoriasis is often preceded by a streptococcal throat infection and T cells specific for streptoccocal superantigens have been identified in the skin. They bind to MHC (Major Histocompatibility) class II molecules and to T-cell receptors (TCR) with certain variable elements of their β-chain. A significant overexpression of Vß- T cells reacting with streptococcal pyogenes, exotoxin C has been found in skin biopsies of patients with acute guttate psoriasis [36, 38].

Bacteria play a role as potent trigger factors of AD, too. The skin of patients with AD is heavily colonized with superantigen-releasing S. aureus bacteria. As a consequence of superantigenic stimulation, T cells in the skin lesions and the blood of these patients show a TCR-Vß expansion [6, 37]. In addition, most patients with AD develop specific IgE antibodies directed against staphylococcal superantigens as a sign for IgE-mediated hyperreactivity to microbial components [3]. Colonziation of the skin with the lipophilic yeast Malassezia sympodialis is a characteristic feature in particular of AD patients with the head-and-neck variant of the disease [39]. In contrast, Malassezia microflora of lesional and non-lesional skin in PSO patients show a different pattern [40].

Defensins

Defensins are cationic antimicrobial peptides (AMP), which have been reported to be involved in the control of skin infections. Within normal skin, these peptides are present at only negligible levels, whereas in response to injury or inflammation, keratinocytes produce high levels of these antimicrobial peptides [41]. In this context, it has been shown that these peptides are dramatically up regulated in psoriatic skin, but not in the skin of patients suffering from AD [42, 43]. This deficiency on the level of antimicrobial peptides in acute and chronic AD skin, might contribute to the increased susceptibility of AD patients to skin infections. Further on AD skin lesions exhibited elevated IL-10 gene expression, which might contribute to the AMP deficiency in AD [43].

Together, all these mechanisms explain why 30% of AD patients suffer from serious skin infections while the frequency of skin infections in Pso patients is rather low [41, 44, 45]. Moreover, it has been shown very recently that overexpression of antimicrobial peptides and plasmacytoid DC (pDC) activation might play a role in the break down of self tolerance to self-DNA and development of autoimmune mechanisms in Pso [46].

Plasmacytoid dendritic cells

It is well-known that Herpes simplex virus infections of the skin, i.e. eczema herpeticum, occur frequently in AD, while they are extremely rare in Pso patients. One of the possible reasons beside the mechanisms which have been described above, might be the role of a distinct population of dendritic cells, the so-called plasmacytoid DC (pDC) in both diseases. Theses cells are characterized by the production of large amounts of type I interferons (interferon-alpha and interferon-beta) upon viral infection. Interestingly, lesional skin samples from patients with Pso contained relatively high numbers of interferon-α producing pDC [47]. In contrast only very few pDC could be detected in the epidermal skin lesions of AD. Several non-mutually-excluding explanations for the low number of pDC in AD can be considered: this could be due to the particular inflammatory, TH2 dominated micromilieu in the skin of AD patients, which may enforce the apoptosis of pDC and/or the alteration of the migratory activity of pDC and the expression of skin homing molecules on the surface of pDC in the peripheral blood of AD patients. In any case, the reported lack of pDC in the epidermis of AD patients may underlie the higher susceptibility of AD patients to viral infections, such as eczema herpeticum, eczema molluscatum or other secondary viral infections of AD lesions compared with Pso [44, 48-50].

T cells

Both diseases are characterized by a chronic skin infiltration with T cells but also with other mononuclear cells such as monocyte-macrophages and dendritic cells. Migration of T cells into the skin and the effector function of T cells are considered as key elements of the pathophysiology of both diseases [32, 38, 51, 52]. T cells are divided into two distinct populations based on their cytokine pattern. TH1 cells secrete IL (Interleukin)-2 and IFN (Interferon)-γ, while TH2 cells produce IL-4, IL-5 and IL-13. In the AD skin, immunhistological features correspond to a TH2 response in the acute stage, while chronic lesions preferably show a TH1 pattern – which predominates in Pso, too [6, 53]. It is likely that a cascade of cytokines, secreted by many different T cells in the local microenvironment of the psoriatic plaque with hyperproliferation of keratinocytes, plays a central role. In Pso, epidermal T cells are for the main part CD8 T cells, dermal T cells are a mixture of CD4 and CD8 cells, with a CD4 predominance [54].

Recently, the pivotal role of a distinct lineage of inflammatory T cells, the so-called TH17 cells, which produce IL-17A, IL-17F, IL-22 and IL-26, as well as IFN-γ and CCL20 in psoriatic skin lesions, has been described [55]. TH17 cells are capable of triggering the production of antimicrobial peptides by epithelial cells and are supposed to be involved in autoimmune responses in Pso [55].

It has been believed over the years that since AD emerges on an atopic, i.e. TH2 background, this disease should be considered as a pure CD4 TH2 disease. However, insights gained by sequential analysis of lesions induced by atopy patch tests strongly imply that AD is not a pure TH2 disease [56]. Moreover, it has been shown recently that CD8 T cells might play a crucial role in the pathogenesis of AD, too [57] since CD8 T cells, forming a mixed TH1/TH2 dermatitis, accumulate in the skin in murine models after exposure to topical superantigens (Staphylococcus aureus) [58]. Further on, Der p-specific CD8 T cells in the blood of AD patients have been shown to produce IFN-γ. Interestingly, there seems to be a strong correlation between the level of specific CD8 T cells in the blood of AD patients and the severity of the disease [59]. Using a mouse model of allergen-induced AD, it has been shown that CD8 T cells are recruited rapidly to the skin, initiating a mixed TH1/TH2 inflammatory immune response [60]. In view of these findings, the TH2 dogma in AD has been profoundly revised during recent years. In summary, it can be postulated that only the initial phase of AD is characterized by a TH2 immune response dominated by TH2 cells, eosinophil recruitment, B cell activation and IgE production. Chemokine production induced by keratinocytes is followed by T-cell infiltration and the development of early skin lesions. The subsequent scratching results in tissue damage and, together with numerous other factors, induces the production of inflammatory mediators, which promote rather TH1-prone inflammation. The resulting chronic phase is a TH0 inflammation, dominated by CD4 and CD8 T cells infiltrating the epidermis and producing, besides other factors, IFN-γ [61]. Since our knowledge about the cytokine and chemokine network in AD is still incomplete, we provide a simplified scheme illustrating the most recent findings in figure 2.

Cytokines and chemokines

Skin

In AD skin lesions an increased expression of a group of CC chemokines has been reported, which are known to attract TH2 cells and eosinophils. In contrast, Pso is primarily associated with increased expression of CXC chemokines, which are known to attract TH1 cells and neutrophils [62].

Indeed, increased expression of chemokine ligand (CCL) 11/eotaxin, CCL13/MCP-4 (Monocyte chemotactic protein), which attracts chemokine receptor (CCR)3-bearing eosinophils, basophils, T cells and CCL17/TARC (thymus and activation-regulated chemokine) has been reported in AD. In addition, increased expression of CCL18/PARC (pulmonary and activation-regulated chemokine) and CCL27/CTACK (cutaneous T cell attracting chemokine) has also been shown [63].

In Pso skin lesions an increased expression of CCL4/MIP-(macrophage inflammatory protein) 1β, which attracts CCR1 or CCR5 bearing TH1 cells and of CXCL-8/IL8, CXCL2/GROß, which attract neutrophils as well as of CCL20/MIP-3α, which recruits CCR6 - bearing TH1-cells has been observed. The CXC chemokine IP10 (Interferon induced protein), which is involved in the chemotaxis of activated T cells and monocytes, and MCP-1 are strongly expressed in lesional keratinocytes of patients with Pso and also partially in the skin of AD patients. Up-regulated expression of RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) and MCP-1 has been detected in the epidermis of patients with both AD and Pso (figure 2) [63-68].

Blood

Plasma levels of IP-10 are significantly higher in Pso than in AD patients and healthy controls [69]. Furthermore, patients with AD demonstrate significantly increased levels of IgE, eosinophilic cationic protein (ECP), and elevated eosinophil levels compared with the levels of patients with Pso. Thus, in the acute phase of AD, high levels of eosinophil chemoattractant mediators such as eotaxin, MDC (macrophage-derived-chemokine), TARC and the soluble (s) CD30-molecule can be observed [70-75]. In the blood of Pso patients CXCR3/CD4 T cells are detectable in high amounts, while in the blood of AD patients CCR4/CD4 T cells are prominent [76]. CTACK/CCL27 serum levels are higher in both patients with AD and Pso. Interestingly, in patients with AD the serum level correlates with the SCORAD (SCORing Atopic Dermatitis) whereas in patients with Pso, no correlation has been found between the serum CTACK level and the PASI (Psoriasis Area Severity Index) [69].

Quality of life

Skin diseases are associated with considerable disabilities. Some studies showed that AD has a greater impact on the quality of life than severe Pso (without joint participation). This could most likely be explained by the pruritus which goes along with AD [77]. In a study comparing AD patients and Pso patients, no differences between AD patients and patients with Pso concerning the stigmatization and quality of life were found [78]. A Swedish study using the health-related quality of life (HRQoL) confirmed this observation. Patients with Pso arthritis had a significantly lower HRQoL than other Pso patients and patients with AD. Furthermore, this study did not find any gender effect on the HRQoL, but a higher age was associated with higher HRQoL in both diseases [79, 80]. A recently published comparative study of the impact of Pso and AD on the quality of life presented a higher score in the attributes ‘daily activity’ and ‘physical discomfort’ in AD patients in comparison to Pso patients, suggesting that pruritus is the dominant factor. In contrast, the scores for ‘self-perception’ and ‘treatment-induced restrictions’ were higher in the Pso group than in the AD group [77].

Recently, education programmes for patients with Pso and AD have been established in different European countries. Standardized interdisciplinary programs involving dermatologists, psychologists/psychosomatic counsellors, and dietary counselling may improve subjective and objective symptoms, help the patients to learn to avoid trigger factors and optimise the use of medications, which might hopefully result in a significant increase in the quality of life of both patient groups.

Conclusion

Comparing the two most frequent chronic skin diseases, AD and Pso, a high number of similarities and differences exist (table 2). Although AD is clinically and pathologically quite distinct from Pso, some features are shared by both diseases. There are at least four gene loci, which are shared by AD and Pso. Both diseases are pathophysiologically driven by T cells and Pso is predominated by TH1-cytokines at least in established lesions, whereas AD is initially predominated by TH2-cytokines at early time points and TH1-cytokines at later time points. Trigger factors such as stress and climate aggravate both diseases. The main steps of therapy, like avoiding trigger factors, skin care and anti-inflammatory treatment, are the same in both diseases. However, from a clinical point of view, most of the features are very different in AD and Pso. Nevertheless, a subgroup of patients with an overlapping form of Pso and AD exists (figure 3).The potential for Pso and AD to coincide has been noted previously, although not all studies agree and some even show an inverse association of both diseases [24]. However, taken together, the dogma that AD and Pso are different and separate diseases could not be reversed, although a high number of features shared by AD and Pso underlie both diseases, and are mainly emphasized by reported common gene loci. But awareness of shared pathophysiological features in both diseases might be helpful for the development of common, effective treatment strategies, such as biologics [81, 82], in the future.
Table 2 Overview of the similarities and differences between AD and Pso

COMPARISON	Pso	AD
	Chronic relapsing inflammatory skin disease	Chronic relapsing inflammatory skin disease
PREVALENCE	– 2% of the world population – No significant changes in annual incidence through the years	– 1-3% in adults; 10-20% in children – Prevalence increased through the past three decades
CLINICAL MANIFESTATION Associations Scores	– see figure 3 – Type 1: before age of 40, HLA associated Type 2: after age of 40, without HLA association – In 5-15% associated with arthritis – sometimes pruritus – PASI (Psoriasis Area Severity Index)	– see figure 3 – Extrinsic form: associated with IgE mediated sensitization intrinsic form without IgE mediated sensitiazation – Frequently associated with allergic rhinitis, asthma and high IgE serum level – Usually pruritus – EASI (Eczema Area Severity Index) and SCORAD (Scoring Atopic Dermatitis)
PROVOCATION- FACTORS Superantigens	– Stress, trauma, infections, medications – Köbner phenomen – Bacteria (streptococcus) overexpression of antimicrobial peptides	– stress, infections, allergies – pruritus with scratching worsen the disease – Bacteria (staphylococcus) – virus – yeast deficit of defensins and plasmacytoid dendritic cells
GENETIC FACTORS	see figure 1 and table 1
HISTOLOGY	see figure 3
PATHO- PHYSIOLOGY	1. The initial activation of T cells through antigens and Antigen presenting cells 2. The migration of T cells to the skin (“trafficking”) 3. the effector function of T cells in the skin by secretion of cytokines and the magnification of the immunologic cascade: - TH1-cytokines - TH17 cells	1. The initial activation of T-cells through uptake of antigens by Antigen presenting cells 2. the migration of T-cells to the skin (“skin-homing”) 3. the effector function of T-cells in the skin by secretion of cytokines and the magnification of the immunologic cascade: – TH2-cytokines in the acute phase/TH1-cytokines in the chronic phase
CYTOKINES	See figure 2
THERAPY	Avoidance of trigger factors Topical therapy – anthralin – corticosteroids – salicylic acid – tars – tazarotene – vitamin D analogues – (CINs)* Phototherapy – UVB – PUVA Systemic treatment** – fumaric acid esters – cyclosporine – methotrexate – acitretin – leflunomide – (mycophenolatmofetil) – (pimecrolimus) – biologics – (antihistamines)	Avoidance of trigger factors Topical therapy – desinfection and/or antibiotics – corticosteroids – CINs* – tars Phototherapy – UVB** – PUVA – UVA * Systemic treatment – antihistamines – corticosteroids – cyclosporin – (methotrexate) – (leflunomide) – (mycophenolatmofetil) – (pimecrolimus) – (biologics)

Acknowledgements

This work was supported by grants of the German Research Council DFG NO454/4-1, SFB704 TPA4 and BONFOR grants of the University of Bonn. N.N. is supported by a Heisenberg-Fellowship of the German Research Council NO454/3-1.

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