Table 1.
Classical vs. Paradoxical psoriasis- differences, similarities, and treatment strategies.
| Characteristics | Classical psoriasis | Paradoxical psoriasis |
|---|---|---|
| Clinico-phenotypic presentation | Well-demarcated erythematous plaques covered with silvery-white scales. | Presence of different psoriatic patterns including plaque-type, guttate, pustular forms as well as eczematiform presentation. Palmoplantar zones affected more often. Non-cicatricial alopecia regularly noted. |
| Histo-pathological appearance | Characteristic psoriatic histology: Epidermal hyperplasia (acanthosis), papillomatosis, hyper-/parakeratosis, dermal, and epidermal immune cell infiltrates. | Three different patterns: -classical psoriatic pattern -eczematiform pattern with spongiosis -lichenoid pattern with interface dermatitis often all these patterns are simultaneously present at variable degrees. |
| Recurrence | Relapsing. | Non-relapsing (upon cessation of anti-TNF). |
| Genetic associations | Many known (and established): HLA-Cw6, IL12B, IL23A, IL23R, and various components along type-I interferon signalling, NF-KB signalling, and other signalling pathways. | Few proposed: IL23R (an allele that is protective concerning classical psoriasis), and FBXL19, CTLA4, SCL12A8, TAPl which have an unclear role in paradoxical psoriasis and the outcome of the allele is undetermined. |
| Role of TNF | Driven by TNF. | Induced by blockade of TNF. |
| Role of adaptive immunity | T-cell mediated. Intraepidermal and dermal (autoimmune) TH/TC17-cells found throughout skin lesions. | T-cell independent. Significant reduced numbers of intraepidermal CD8+ TC-cells as compared to classical psoriasis. |
| Role of innate immunity | Transiently driven by pDC derived type-I IFN during the early phase of psoriasis development. Mature cDCs and neutrophils present in large numbers in skin lesions of chronic/late phase of classical psoriasis. | Driven by unabated type-I IFN produced by non-maturing pDCs. Immature dendritic cells, and neutrophils often present in lesions. Role for other cell types not known (particularly in mediating the psoriatic phenotype). |
| Pathogenic mechanism | Chronic (autoimmune) TH/TC17-mediated inflammation | Unabated, ongoing type-I IFN-driven innate inflammation, absence of T-cell autoimmunity. |
| Treatment avenues | -targeting TNF highly effective | -switch to different class of biologics (other than anti-TNF) often needed in severe cases of paradoxical psoriasis |
| Various other treatment strategies validated: | In the absence of detailed knowledge about the pathogenic pathways, proposition of: | |
| -targeting of IL-12/IL-23 highly effective -targeting of IL-23 highly effective -targeting IL-17A and its receptor highly effective -targeting type-I interferon is ineffective in established classical chronic plaque-type psoriasis. |
-use of anti-IL12/IL23 (successful in case reports) -unknown efficacy of IL-23 specific biologics -unknown efficacy of targeting IL-17A and its receptor -targeting type-I interferons and/or pDCs potentially effective |