**2. Psoriasis and skin comorbidities**

### **2.1 Psoriasis and vitiligo**

Vitiligo is the most common disorder of pigmentation. Although the association of psoriasis and vitiligo has been described since 1890, the interrelationship between the two dermatoses remains debatable. Most of the studies found that 6% of patients with vitiligo develop psoriasis [4, 5] and 2% of patients with psoriasis suffer from vitiligo [4]. Furthermore, a clinical and even dermoscopic challenge is to distinguish vitiligo from the occurrence of hypopigmentation in areas of previously affected psoriatic

skin [6]. Healing of psoriatic lesions often leaves hypopigmentation that could simulate vitiligo. There have been cases reported in the literature of psoriatic plaques and guttate lesions strictly localized to the vitiliginous patches (**Figure 1**), and the two dermatoses occurring together without strict colocalization of lesions. In many cases, it is difficult to say which disease starts first, vitiligo, or psoriasis, or may occur at the same time. A retrospective study found that almost 47% of patients having both diseases had separated lesions [7], while, in another study, 34% of patients' psoriatic plaques covered the vitiligo patches [8].

Many hypotheses tried to explain the pathogenesis of vitiligo. These hypotheses consider the role of neural implication, microvascular anomalies, melanocyte degeneration from oxidative stress, defects in melanocyte adhesion, autoimmunity, somatic mosaicism, and genetic influences [9]. Genetic and immunological factors are present in both diseases, psoriasis and vitiligo. A study in China found that both skin diseases share a common genetic locus in the major histocompatibility complex (MHC) [10]. Precisely, the rs. 9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing the first substantial evidence that two different skin diseases share a common genetic locus in the MHC. In the molecular etiopathogenesis mechanism of both diseases, Th1 cytokines play a key role. Vitiligo and psoriasis are both chronic inflammatory Th1 type autoimmune diseases with increased TNF-α and interferon γ levels [8]. Otherwise, both share the activation of the Th17 pathway [11]. Even more,

#### *Psoriasis and Skin Comorbidities DOI: http://dx.doi.org/10.5772/intechopen.102320*

the memory cells might be a link between psoriasis and vitiligo. Recent translational research shows the presence in psoriatic skin of memory CD8+ T cells directed against the melanocyte-derived protein ADAMTSL5 [12], a protein that may favor the development of vitiligo in a predisposed patient. The tissue-resident memory T (TRM) cells are also vital in the recurrence of chronic inflammatory skin disorders, including psoriasis and vitiligo, under pathological or uncontrolled conditions [13].

An interesting phenomenon is the case of vitiligo induced by biological drugs used for psoriasis treatment. The anti-TNF-α (etanercept, infliximab) is one of the most cited groups of biological drugs that induce new-onset vitiligo or progression of pre-existence vitiligo in psoriatic patients [14]. Even anti-IL12/23 [15] and anti-IL17 [15, 16] class can induce a progression of pre-existing vitiligo, while, to date, no cases are reported in the literature considering anti-IL23 drugs. It is difficult to understand how molecules that block cytokines involved in both diseases' pathogenesis can trigger the mechanisms underlying this phenomenon. However, a new type of medication that functions by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2), thereby interfering with the JAK-STAT signaling pathway, have been approved for psoriatic therapy and are also a promising novel therapy for vitiligo.

In conclusion, the paucity of data on the link between psoriasis and vitiligo underlines the gaps of knowledge on this topic. To highlight the pathogenetic mechanisms underlying the two diseases are strongly needed further studies.

#### **2.2 Psoriasis and alopecia areata**

Psoriatic lesions of the scalp are sometimes associated with symptomatic hair loss and alopecia. The type of alopecia can be, in most cases, characterized using the dermatoscope.

Alopecia areata (AA) is the most common immune-mediated hair loss disorder with a lifetime prevalence of 2% [17]. Early studies of the last decade showed that patients with psoriasis and psoriatic arthritis have a higher risk to develop other autoimmune disorders, particularly alopecia areata (AA) [1, 18]. Two large population studies demonstrated an odds ratio of 2.4 [1, 18].

The Renbeok phenomen, the opposite of the Koebner phenomenon, was originally described in AA patients where hair growth was observed in psoriatic plaques. Generalizing, it is an interesting phenomenon where one skin condition inhibits other skin conditions and confirms once again the complex immunological overlap between these two skin diseases.

In the case of a patient with psoriasis and AA, the complexity of the common immunological paths that share these both skin disorders must be considered when selecting therapeutic regimens, to avoid worsening one of their inflammatory conditions while treating the other. For example, contrary to the initial hope that tumor necrosis factor α (TNFα) may have a role in the pathogenesis of AA, many reports have demonstrated the inefficiency of anti-TNFα drugs in the treatment of AA [19].

Moreover, careful selection of biological treatment regimens may offer therapeutic benefits for both their psoriasis and AA while giving us experience with the newer biologics in AA. The investigation of cytokine profile and the relation between different categories of cytokines is continuing in both psoriasis and AA. A recent example comes from a recent study where the authors conclude that psoriasis T helper type 17 (Th17) cytokines can inhibit some inflammatory processes involved in AA pathogenesis [20].

#### **2.3 Psoriasis and bullous diseases**

Autoimmune bullous diseases (AIBD) and more frequent pemphigoid group, often develop in patients with psoriasis. The rare nature of AIBD makes collecting epidemiologic data with a representative number of patients a laborious process. Among the pemphigoid diseases, bullous pemphigoid (BP), the most prevalent subcutaneous autoimmune bullous disease worldwide, is also the most prevalent blistering disease associated with psoriasis. This association has been studied and confirmed on large populations [21–24]. BP and psoriasis do not share any common HLA or otherwise genetic susceptibility. A consequence of epigenetic events related to the psoriatic inflammatory cascade and changes at the basal membrane zone in psoriasis is possible pathogenetic hypotheses, along with increased of certain Th1/Th17 cytokines and chemokines levels that may be another link for their association [25].

Antilaminin γ1 pemphigoid is the second most prevalent AIBD associated with psoriasis, followed by the combination of BP with antilaminin γ1 pemphigoid [26]. The explanation of the subepidermal blister formation in psoriatic patients is mainly provided by Mondello and Vaccaro studies [27, 28]. The cleavage and disruption of laminin 1 and laminin α1 within basal membrane zone, either in apparent normal skin or psoriatic lesion [27, 28], might be the main trigger factor for several antibodies production, such as anti-laminin γ1 and anti bullous pemphigoid antigen 180 (BP180). As a result, the development of BP rash is sometimes observed in psoriatic patients. In the same case series of Ohata et al. [26], three patients presented linear IgA bullous dermatosis and two epidermolysis bullosa acquisita.

The relation between psoriasis and BP seems to be bidirectional. The only published study that confirms that psoriasis occurs significantly more frequently in patients with BP than in the control group, comes from Taiwan [21]. Large population studies in each country are necessary to support this association.

Mucous membrane pemphigoid is also a rare chronic autoimmune disorder characterized by subepidermal blistering that has been observed in patients with psoriasis [29]. The laminin degradation stimulated by matrix metalloprotease 9 released from neutrophil infiltrate in the patients with psoriasis may contribute to decreasing the threshold of autoantibodies against laminin γ1 production [30, 31].

A recent systematic review and meta-analysis evaluating the association between pemphigus and psoriasis confirm this association [32]. However, it is difficult to find common pathways between pemphigus and psoriasis pathophysiologic mechanisms.
