SEARCH

SEARCH BY CITATION

ORIGINAL ARTICLE, p 59

Psoriasis is an inflammatory skin disease with variable morphology, distribution, severity and clinical course. There is a wide spectrum of cutaneous manifestations of psoriasis. Individual lesions vary from pinpoint to large plaques, or even generalized erythroderma. More specifically, phenotypic variants of psoriasis include the plaque, guttate, small plaque, inverse, erythrodermic and pustular forms.[1] These clinical phenotypes are heterogeneous not only for their morphology but also for the type of inflammation and histology. Thus, a neutrophilic infiltrate is highly represented in pustular psoriasis, whereas mononuclear cells and T lymphocytes are preferentially present in stable psoriatic plaques.[2] A different pattern of inflammation is also revealed in the so-called ‘early’ and ‘late’ psoriatic lesions. In early psoriasis, cells of the innate immunity, such as neutrophils, activated mast cells and interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs) predominate, whereas T lymphocytes and mononuclear cells characterize late psoriatic lesions.[3, 4] In addition, heterogeneity can be found within the same psoriatic lesion, as revealed in inhomogeneous psoriatic plaques, showing both acute and chronic inflammatory areas, characterized by neutrophilic and mononuclear infiltrates, respectively.[5] Coexistence of late and early inflammation signs inside psoriatic plaques also occurs, with these signs seen, respectively, in the Munro neutrophilic microabscesses in the cornified layer, and in dermal ‘squirting papillae’, originating active immune cells and occurring intermittently at timely intervals.[5]

According to the interesting point of view of Christophers et al., described in this issue of BJD,[6] the clinical and histological heterogeneity of psoriasis could reflect the temporal alternation of an initial ‘autoinflammatory’ phase – where cells of the innate immune system together with aberrant activation of interleukin-1 and inflammasomes prevail – and an adaptive phase, characterized by the presence of (auto)reactive T lymphocytes, mostly T helper (Th)17 and Th22 in the beginning and type-1 IFN-γ-producing T cells during the chronicization of the disease. In keeping with this view, autoinflammatory responses predominate in exanthematic and pustular psoriasis, in the early psoriatic lesions, including pre-pinpoint papules of developing psoriasis or lesions triggered by the Koebner phenomenon, as well as in psoriatic linear nail pitting, where the periodic neutrophilic bursts cause the typical production of keratin masses/pits in the nails.[7, 8] In contrast, type-1-dominated autoimmune responses characterize stable psoriatic plaques, where neutrophils are present exclusively in the Munro microabscesses. On the other hand, during the progression of stable plaque-type psoriasis, at the peripheral sites of lesions in close proximity to normal-appearing skin, a mixed pattern of inflammation may coexist with autoinflammatory foci interspersed into areas of mature T-cell-rich infiltrate.[5]

Accepting that psoriasis is a disease characterized by a bimodal immune activation, as the review's authors propose,[6] it is not surprising that the results from therapeutic interventions are variable, and reflect different stages of psoriasis and relative inflammatory activity. For instance, this model explains why treatment with tumour necrosis factor-α blockers, which are thought to be active mainly on innate immunity, is effective in about 75% of cases, and why the responsiveness to topical corticosteroids sometimes differs within the same psoriatic lesion, with chronic areas responding well to therapy while areas characterized by acute inflammation tend to be resistant.[5] The bimodality of immune activation in psoriasis is also supported by clinical observations whereby drug-induced agranulocytosis completely clears psoriasis and, on the contrary, treatments inducing Th1-type immunity, such as IFN-α or imiquimod (a Toll-like receptor agonist that triggers production of IFN-α by pDCs), exacerbate psoriasis.[9, 10]

According to the proposed model that psoriasis is a disease where adaptive and immune responses are associated, but temporally integrated only for a short time (expected during the Th17 and Th22 bursts) and then become distinct, the therapeutic intervention should take into account the specific phase and type of inflammation dominating the psoriatic lesions being treated. Moreover, a two-phased combined therapy, aimed at suppressing both innate and adaptive immune responses, would be helpful for the treatment of inhomogeneous psoriatic plaques.

Conflicts of interest

None declared.

References

  1. Top of page
  2. References
  • 1
    Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370:26371.
  • 2
    Murphy M, Kerr P, Grant-Kels JM. The histopathologic spectrum of psoriasis. Clin Dermatol 2007; 25:5248.
  • 3
    Nestle FO, Conrad C, Tun-Kyi A et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 2005; 202:13543.
  • 4
    Albanesi C, Scarponi C, Pallotta S et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J Exp Med 2009; 206:24958.
  • 5
    Griffin TD, Lattanand A, VanScott EJ. Clinical and histologic heterogeneity of psoriatic plaques. Therapeutic relevance. Arch Dermatol 1988; 124:21620.
  • 6
    Christophers E, Metzler G, Röcken M. Bimodal immune activation in psoriasis. Br J Dermatol 2014; 170:5965.
  • 7
    Jablonska S. Immunological mechanisms in psoriasis: role of polymorphonuclear leukocytes. In: Psoriasis (Farber EM, Nall L, Morhenn V, Jacobs PH, eds). Amsterdam: Elsevier, 1986; 1317.
  • 8
    Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell 2010; 140:78490.
  • 9
    Toichi E, Tachibana T, Furukawa F. Rapid improvement of psoriasis vulgaris during drug-induced agranulocytosis. J Am Acad Dermatol 2000; 43:3915.
  • 10
    Ketikoglou I, Karatapanis S, Elefsiniotis I et al. Extensive psoriasis induced by pegylated interferon alpha-2b treatment for chronic hepatitis B. Eur J Dermatol 2005; 15:1079.