Psoriasis review study

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SCIENTIFIC RESEARCH GATE
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International Journal of Internal Medicine Papers 2017; 2 (1): 1–5
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Etiopathogenesis of Psoriasis; Role of Genetic, Immunologic and
Environmental Factors; A Review
Maruf Raza AKM1
*, Mahfujun Nahar2
1. Assistant Professor of Pathology, Jahurul Islam Medical College, Bajitpur, Kishoregonj, Bangladesh.
2. MBBS, FCPS (P-1), Medical Officer, Jahurul Islam Medical College, Bajitpur, Kishoregonj, Bangladesh
Abstract
Psoriasis is a chronic inflammatory papulosquamous disease characterized by multiple remissions and relapses. Although a lot is
known regarding its pathogenesis, much remains to be elucidated and understood. For long, it was believed to be primarily a
disorder of keratinization. However, the successful use of traditional immunosuppressants and newer immunomodulatory agents
in the treatment of psoriasis led to the belief that psoriasis is primarily a disease of Th1 cell immune dysregulation. Recent
developments have brought up several new findings such as the role of Th17 cells and evidence of skin barrier dysfunction in
psoriasis, akin to atopic dermatitis. The present review aims to focus on these new developments and explain the pathogenesis of
psoriasis on the basis of currently available information.
Key words: Psoriasis, Skin barrier, Keratinization, Papulosquamous
Citation to This Article: Maruf Raza AKM, Nahar M. Etiopathogenesis of Psoriasis; Role of Genetic, Immunologic and Environmental Factors;
A Review. International Journal of Internal Medicine Papers 2017; 2 (1): 1–5.
1. Introduction
Psoriasis affects nearly 2-3% of the world's population and presents as erythematous, indurated, scaly plaques over
the skin sometimes with involvement of the nails and joints (1). It is characterized by exaggerated and disordered
epidermal cell proliferation and keratinization. Though tremendous leaps have been made in our understanding of the
disease, the chain of events that culminates in this aberrant keratinization has not yet been elucidated. A host of
abnormalities seen in psoriasis, like increased levels of cyclic - adenosine monophosphate (cAMP), epidermal growth
factor receptor binding, protein kinase C and transforming growth factor-α (TGF-α), collectively point to a disturbance
in T cell function (2). Currently, the most accepted hypothesis is that psoriasis is an immune-mediated inflammatory
skin disease that manifests in a genetically predisposed person exposed to certain environmental agents or triggers.
This view has been reinforced by the efficacy of various immunomodulatory agents in the treatment of psoriasis (3).
Recent findings such as the presence of a barrier defect in psoriasis and the proinflammatory role of
NLR/CATERPILLAR (nucleotide binding domain) family of genes and microbial flora have again shifted the focus
from T lymphocytes to keratinocytes as the cells of prime importance in the pathogenesis (4). This review aims to
discuss the role of various factors, genetic, environmental and immunologic, that are central to the pathogenesis of
psoriasis.
2. Epidemiology and Clinical Features of Psoriasis
Although psoriasis occurs worldwide, its prevalence varies considerably. In the USA, approximately 2% of the
population is affected. The prevalence of psoriasis is low in certain ethnic groups such as the Japanese, and may be
* Corresponding author: Dr. A K M Maruf Raza
Tel: +8801711306123
E-mail address: drmarufraza@gmail.com

2. Maruf Raza A.K.M & Nahar M. International Journal of Internal Medicine Papers 2017; 2 (1): 1–5
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absent in aboriginal Australians (2) and Indians from South America (5).Psoriasis can present at any age and has been
reported at birth and in older people of advanced age. A bimodal age of onset has been recognized in several large
studies. The mean age of onset for the first presentation of psoriasis can range from 15 to 20 years of age, with a
second peak occurring at 55–60 years (6). In addition, strong associations have been reported with human leucocyte
antigen (HLA)-Cw6 in patients with early onset, compared with later onset of psoriasis. The course and progress of
psoriasis is unpredictable. In one study, 39% of patients reported complete remission of disease for between one and
54 years (7).
Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course. Papulosquamous
diseases are characterised by scaling papules (raised lesions <1 cm in diameter) and plaques (raised lesions >1 cm in
diameter). Scale is typically present in psoriasis, is characteristically silvery white, and can vary in thickness. Removal
of scale may reveal tiny bleeding points (Auspitz sign). The lesions of psoriasis are distinct from other entities and
are classically very well circumscribed, circular, red papules or plaques with a grey or silvery-white, dry scale. In
addition, the lesions are typically distributed symmetrically on the scalp, elbows, knees, lumbosacral area, and in the
body folds. Psoriasis may also develop at the site of trauma or injury, known as Koebner’s phenomenon. If psoriasis
is progressive or uncontrolled, it can result in a generalised exfoliative erythroderma. Nail involvement may be present,
particularly if psoriatic arthritis (PsA) is present. In addition, these different forms of psoriasis may be localized or
widespread and disabling. Further, psoriasis may have a variable course presenting as chronic, stable plaques or may
present acutely, with a rapid progression and widespread involvement (8).
3. Environmental Factors in Pathogenesis
It is clear that environmental factors are involved in the expression of the disease. Several factors, such as physical
trauma, psychological stress, drugs and infections, may trigger the disease in a genetically predisposed individual (9).
Certain drugs can cause drug triggered psoriasis (i.e. induction of psoriatic lesions on clinically uninvolved skin in
patients with psoriasis) as well as drug induced psoriasis (i.e. precipitation of the disease in genetically predisposed
individuals). Although a plethora of drugs have been implicated in provoking psoriasis, the strongest evidence is for
lithium, beta-blockers, anti-malarials, non-steroidal anti-inflammatory drugs and tetracyclines. In addition,
angiotensin-converting enzyme inhibitors, interferons, digoxin, clonidine, carbamazepine, valproic acid, calcium-
channel blockers, granulocyte-colony stimulating factor, potassium iodide, ampicillin, penicillin, progesterone,
morphine and acetazolamide have been reported to exacerbate psoriasis. In one study, staphylococcal super antigens
were isolated from 17% of a group of 111 patients who showed a sudden onset or aggravation of psoriasis (10).
Psoriasis is one of the dermatosis where the occurrence of Koebner's phenomenon (KP) has been well documented
and studied in detail. The time interval between injury and onset of psoriasis varies from 3 days to 2 years. The factors
that contribute to Koebnerisation include season (seen more frequently in winter than in summer) and disease severity
(more in unstable or flaring disease). It has been suggested that trauma has to cause both epidermal cell injury and
dermal inflammation to produce KP (11).
4. Immunological Factors in Pathogenesis
The earlier concept of psoriasis being solely a T‑helper (Th1) mediated disorder has been replaced by the concept of
combined Th1 and Th17 mediated inflammatory disease (12). The recognition of this new subset of helper T‑cells
(Th17) and Th22 cells and their distinct sets of cytokines (interleukin; IL-23, IL‑22) has opened up research for newer
specific drugs. Decreased suppressive activity of regulatory T‑cells seen in psoriatic lesions possibly leads to
uncontrolled action of the other effector cells. Hence, psoriasis is now more considered as the outcome of complex
interactions within various subsets of T‑cells instead of being a disease caused by a single subset. These T‑cells are
possibly activated by antigens presented by the dendritic cells of the skin (Langerhans cells, dermal dendritic cells,
myeloid, and plasmacytoid dendritic cells) (13). The streptococcal M protein bears a structural similarity with the
Type 1 keratins and may thus stimulate an immune reaction which can then cross react with specific tissue antigens
in the skin, a concept known as molecular mimicry. Recognition of streptococcal peptidoglycan through pattern
recognition receptors such as Toll‑like receptor 2, and PG recognition proteins 1–4 is another mechanism of psoriasis

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induction due to altered immune response (14). These molecular mechanisms possibly underlie the beneficial effects
of tonsillectomy in some cases of psoriasis which show aggravation after episodes of streptococcal infections (15).
The other immune cells such as macrophages produce tumor necrosis factor (TNF)‑α, proteases, growth factors, and
vascular endothelial growth factor (VEGF), which in turn perpetuate the inflammatory process and promote
angiogenesis. Mast cells similarly produce large quantities of TNF‑α, interferon (IFN)‑γ, IL‑8, and VEGF causing
recruitment of T‑cells and neutrophils at inflammation site (16). Neutrophil activation appears to be important,
especially in early and active psoriatic lesions though its role has not been clearly elucidated. Activated neutrophils
degranulate to release a large amount of cytokines, proteases and elastases, cationic proteins (lactoferrin, etc.,), and
play an important role in recruitment and activation of T‑cells to the lesional site (17).
These cytokines and other inflammatory mediators produced by the T‑cells, dendritic cells, neutrophils, and
macrophages activates the keratinocytes which increase their proliferation and in turn produce various cytokines and
growth factors to maintain keratinocytes proliferation.
5. Genetic Factors in Pathogenesis
Many authors have school of thoughts that psoriasis results from the interplay of multiple genes. The drawback of this
hypothesis is that although the psoriasis susceptibility genes are located in numerous loci throughout the genome,
these locations vary among different populations and families, and the results are difficult to replicate. Goilhou et al.
hypothesize that the same genes may be present at these different loci as "jumping genes or retrotransposons" (18).
PSORS1 is present in the HLA Class I region of chromosome 6p and accounts for 35-50% of heritability of the disease.
HLA-C-06 is the most likely susceptibility gene in the PSORS1 region and given its important role in antigenic
presentation, the association reflects the role of the adaptive immune response in psoriasis (19). The locus also
harbours the corneodesmosin (CDSN) gene, which encodes a protein expressed in differentiated keratinocytes and is
considered a genetic risk factor for psoriasis development. Since PSORS1 harbours both the CDSN gene and HLA-
C-*06, it is quite possible that both adaptive immunity and defective barrier function are involved in the pathogenesis
of psoriasis (20). Significant associations have also been found in gene regions involving specific inflammatory
pathways, namely, IL-23 signaling (IL-23A, IL-12B and IL-23R), modulation of Th2 immune responses (IL-4 and
IL-13), and nuclear factor (NF) κB signaling (21). Other associations include epidermal defense genes, DEFB4 (copy
number variation [CNV] of a genomic segment on chromosome 8p23.1 harboring a cluster of DEFB genes, encoding
β-defensins), and late cornified envelope proteins 3B (LCE3B) and 3C (LCE3C) (a CNV in the PSORS4 region on
chromosome 1q21 encoding their deletion) (22). These genes are expressed in epithelial cells but not on immunocytes.
Marrakchi et al. observed that homozygous missense mutation in the IL36RN gene on chromosome 2q13-q14.1,
encoding for IL-36 receptor antagonist was associated with an unregulated secretion of inflammatory cytokines and
an increased predisposition to develop generalized pustular psoriasis (23). The role of the NLR/CATERPILLAR
(nucleotide binding domain) family of genes in psoriasis has also been studied. These encode important mediators of
innate immunity and are concerned with maintaining epidermal barrier function and initiating pathogenic responses
to environmental microbes (24).
6. Role of Impaired Skin Barrier in Pathogenesis
The skin acts as a two-way barrier to prevent the inward or outward passage of water and electrolytes. The barrier is
largely situated in the epidermis, isolated epidermis being as impermeable as whole skin, whereas once the epidermis
is removed the residual dermis is almost completely permeable. The epidermal barrier is localized to the stratum
corneum. The barrier depends on both the cornified material of the keratinocytes and the intercellular material,
particularly lipids. An intact stratum corneum prevents invasion of the skin by normal skin flora or pathogenic
microorganisms. Minor injury in the skin and skin diseases can provide portals of entry to microorganisms, particularly
Streptococci or Staphylococci. The abnormal keratinization in psoriasis is seen as an increased expression of early
differentiation markers such as CDSN and small proline rich proteins, cystatin A and transglutaminase 1, and
decreased expression of late differentiation markers such as loricrin and filaggrin. This leads to aberrant formation of
the cornified envelope that in turn affects the barrier capacity of the skin. This manifests as increased transepidermal

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water loss, which is directly proportional to the clinical severity. The expression of aquaporins, a family of water
transporting proteins present in the plasma membrane of the stratum corneum and the stratum spinosum, is decreased
in lesional and perilesional skin in psoriasis (25). The LCE gene cluster, which is composed of six groups (LCE 1-6,
with a total of 18 members) is a part of the epidermal differentiation complex. Its deletion has been strongly linked
with psoriasis. It has been speculated that deletions of LCE3B and LCE3C genes lead to incomplete barrier repair after
minor trauma, which in turn causes penetration of various antigens and induces an inflammatory response (26).
7. Conclusion
Psoriasis is a complex disease. Ongoing research regarding psoriasis has left us with a problem of plenty. There is a
huge array of potential genes implicated and an equally large array of molecules (chemokines, cytokines, inflammatory
mediators, signal transduction molecules, and transcription factors) involved. New therapeutic options have opened
up and thorough understand of the disease process will help their optimal utilization. Hopefully, with increasing
research, it will be possible to provide more effective and individualized treatment to patients of psoriasis.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
There are no conflicts of interest.
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