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SPOTLIGHT ON PSORIASIS
Year : 2013  |  Volume : 58  |  Issue : 4  |  Page : 294-298
A study of various histopathological features and their relevance in pathogenesis of psoriasis


Departments of Pathology and Dermatology, Armed Forces Medical College, Pune, India

Date of Web Publication25-Jun-2013

Correspondence Address:
Manas Chatterjee
Department of Pathology and Dermatology, Command Hospital (Eastern Command), Kolkatta - 700 027
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.113948

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   Abstract 

Background: The pathogenesis of psoriasis is still to be fully unraveled. The immunological theory with T cells at the centre of attraction and peripherally acting cytokines are the present favourites among aetiopathological factors. Histopathology of the skin lesions offers a good study model to understand the pathogenesis of this complex disease. Aims: To study the various histopathological parameters of psoriatic lesions, and to establish their correlation with the pathogenesis of the disorder. Materials and Methods: Eighty eight consecutive histopathologically proven cases of psoriasis were included in the study. Eight common histopathological parameters of psoriasis present in these biopsies were assessed and graded. We then statistically analyzed the relationship of the factors with one another and attempted to establish a better understanding of the pathogenesis of disease. Results: Significant correlations were found between degree of epidermal hyperplasia and inflammatory infiltrate, grade of inflammation and pustules of Kogoj, inflammatory infiltrate and grade of capillary proliferation as also between epidermal hyperplasia and the presence of parakeratosis. Conclusion: The study suggests that the immunopathogenesis of psoriasis is predominantly based on the inflammatory response. This is in consonance with other studies which have suggested that psoriasis is primarily a T lymphocyte based disease. Several treatment modalities are now based on this concept and it is hoped that the future treatment modalities will focus on the central role of inflammatory cells in the pathogenesis of this enigmatic disease.


Keywords: Epidermal hyperplasia, histopathology, inflammation pathogenesis, psoriasis


How to cite this article:
Moorchung N, Khullar J S, Mani N S, Chatterjee M, Vasudevan B, Tripathi T. A study of various histopathological features and their relevance in pathogenesis of psoriasis. Indian J Dermatol 2013;58:294-8

How to cite this URL:
Moorchung N, Khullar J S, Mani N S, Chatterjee M, Vasudevan B, Tripathi T. A study of various histopathological features and their relevance in pathogenesis of psoriasis. Indian J Dermatol [serial online] 2013 [cited 2019 Dec 11];58:294-8. Available from: http://www.e-ijd.org/text.asp?2013/58/4/294/113948

What was known? 1. The common pathologies observed in psoriatic lesions are: epidermal proliferation, dilatation of superficial dermal capillaries and inflammatory infiltration in the papillary dermis. 2. T cells play a very important role in aetiopathogenesis of psoriasis.



   Introduction Top


Although psoriasis vulgaris is usually identified by the clinical appearance of characteristic red, raised, scaly skin lesions, it is best defined as a unique skin disease by a set of underlying cellular changes. Clinical features, then, are explained by impressive growth and dilation of superficial blood vessels (redness) and equally impressive hyperplasia of the epidermis. Epidermal growth occurs in a pattern termed "psoriasiform" hyperplasia, which describes both elongated rete pegs, thickening (acanthosis), and differentiation changes. In psoriatic epidermis, keratinocytes proliferate and mature rapidly. Hence, squamous keratinocytes aberrantly retain intact nuclei (parakeratosis). [1]

Whether psoriasis represents a fundamental disease of skin, or the immune system, has been debated for several years. It is commonly accepted that the two major pathological lesions observed in psoriasis are epidermal hyperproliferation with abnormal differentiation, and an inflammatory infiltration of the epidermis and dermis. [2] In the past, therapies for psoriasis had focused on treating epidermal hyperplasia, which was hypothesized to occur as a result of the abnormal proliferation and differentiation of basal keratinocytes. [3] It later became evident that there was a direct role for T cells in the pathogenesis of psoriasis. [4]

In the past decade researchers have come up with new factors that may be involved in the pathogenesis of disease, but they have failed to establish a model that incorporates all these factors. In this paper, we describe a study in which we studied the histopathology of a series of cases of psoriasis and graded the various histopathological parameters. We then statistically analyzed the relationship of the factors with one another. With this data, we have attempted to establish a better understanding of the pathogenesis of disease.


   Materials and Methods Top


Patient selection

All patients with a clinical diagnosis of psoriasis were subjected to a biopsy. Biopsies were taken from the lesion to include the perilesional skin. Only patients with a histopathological diagnosis of psoriasis were then included in the study.

Histopathology

Biopsies were taken from the lesion to include a small portion of the perilesional skin. The biopsies were immediately fixed in formalin for histopathological examination. Sections were stained with the standard Haematoxylin and Eosin stain using standard histological laboratory methods. Histopathological analysis of the biopsies was done and included eight criteria (epithelial hyperplasia, parakeratosis, Munro's and Kogoj's microabscesses, suprapapillary thinning, inflammatory infiltrate, widened rete ridges and capillary proliferation). Grading was done using a visual analogue scale and the biopsies were graded as 0 to 3 (Nil to marked).

Hyperkeratosis

It was defined as the thickening of the stratum corneum. It was graded on a scale of 1 to 3 i.e., - mild to marked [Figure 1].
Figure 1: Grades of hyperkeratosis (a) Grade 1 - mild (b) Grade 2 - moderate (c) Grade 3 - marked. (H and E stain, ×40)

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Parakeratosis

It was defined as the presence of keratinisation with retained nuclei in the stratum corneum. It was graded as present or absent.

Munro's microabscesses and pustules of Kogoj

These were defined as the presence of collections of neutrophils in the corneal layer and the stratum spinosum respectively. They were graded as present or absent.

Suprapapillary thinning

This was defined as a thinning of the granular layer at the tips of the papillae. The elongation of the rete pegs was also considered in this factor. It was graded on a visual analogue scale as 0 to 3 (nil to marked) [Figure 2].
Figure 2: Suprapapillary thinning (a) Grade 1 - mild (b) Grade 2 - moderate (c) Grade 3 - marked. (H and E stain, ×40)

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Inflammatory infiltrate

The degree of the inflammatory infiltrate in the dermis was graded on a visual analogue scale as 0 to 3 (nil to marked) [Figure 3].
Figure 3: Inflammatory infiltrate (a) Grade 1 - mild (b) Grade 2 - moderate (c) Grade 3 - marked. (H and E stain, ×4)

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Capillary proliferation

This factor analyzed the proliferation and dilatation of the capillaries at the tips of the papillae. It was not possible to use morphometry for the grading and so it was graded on a visual analogue scale as 0 to 3 (nil to marked) [Figure 4].
Figure 4: Capillary dilatation (a) Grade 1 - mild (b) Grade 2 - moderate (c) Grade 3 - marked. (H and E stain, ×40)

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Statistical analysis

The SPSS package for Windows (version 13) was used for statistical analysis. The Chi square test for association between different parameters has been used for the present study.


   Results Top


Demographic variables

88 cases were analyzed in the present study. The mean age was 38.9 years with a range of 13 to 76 years. 48 males and 40 females comprised the study population.

Epidermal hyperplasia

The grade of epithelial hyperplasia and hyperkeratosis showed a strong correlation with parakeratosis (P = 0.001), pustules of Kogoj ( P = 0.038) and the inflammatory infiltrate ( P = 0.007) [Table 1] and [Figure 5]. There was however no correlation with the presence of Munro's microabscesses or with suprapapillary thinning. There was also a correlation with the presence of capillary proliferation at a slightly lower P value ( P = 0.080).
Table 1: The association between various histopathological parameters in psoriasis


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Figure 5: Box whisker plots showing correlation between epidermal hyperplasia and other histopathological parameters in psoriasis

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Parakeratosis

Except for the correlation with epidermal hyperplasia, the presence of parakeratosis did not show a significant correlation with any of the other histopathological parameters.

Munro's microabscesses and pustules of Kogoj

Munro's microabscesses showed a significant correlation only with the pustules of Kogoj. There was no correlation with any of the other histopathological parameters. The pustules of Kogoj showed a significant correlation with the grade of epidermal hyperplasia and the inflammatory infiltrate ( P = 0.038 and 0.003 respectively). There was no correlation with any of the other histopathological parameters.

Suprapapillary thinning

This showed a significant correlation with the inflammatory infiltrate and the degree of capillary proliferation ( P = 0.001 in both cases). There was no other significant correlation with any of the histopathological parameters.

Inflammatory infiltrate

In addition to the above factors, the inflammatory infiltrate also had a significant correlation with the degree of capillary dilatation ( P = 0.001) [Figure 6].
Figure 6: Box whisker plots showing correlation between inflammatory infiltrate and other histopathological parameters in psoriasis

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Capillary proliferation

The grade of capillary proliferation showed a significant correlation with the inflammatory infiltrate and the grade of suprapapillary thinning.


   Discussion Top


The inflammatory infiltrate appears to be the central reason for the entire pathogenesis of psoriasis. There was a significant correlation of epidermal hyperplasia with the inflammatory infiltrate, pustules of Kogoj, capillary proliferation and parakeratoses in our study. It is widely believed that abnormal regulation of T cells coupled with interaction between keratinocytes and complex cytokine network is involved in the pathogenesis of the disease. [5],[6],[7]] An injury to the defective keratinocytes could activate synthesis and release of cytokines. These cytokines potentiate T lymphocyte activation to a greater extent than cytokines secreted from normal epidermal cells. [8] This would lead to secretion of cytokines and various growth factors by the T cells, further proliferation of keratinocytes and thus establish a vicious cycle of events. This cycle would explain our observation that there was a significant correlation between the degree of epidermal hyperplasia and the inflammatory infiltrate.

We noted a significant correlation between the grade of the inflammation and the pustules of Kogoj. There was however no correlation with the microabscesses of Munro. This is probably because the Kogoj's pustules are closer to the dermis than the Munro's microabscesses. It is thought that neutrophils are recruited by the neutrophil-attracting chemokine interleukin-8 (CXCL8). IL 8 mRNA is known to be synthesized by the CD 4 subset of T cells. [9] We believe that it is the IL 8 secretion which recruits neutrophils. These neutrophils then migrate through the epidermis. Kogoj's pustules indicate a recent recruitment since they are in the lower reaches of the epidermis and that would explain the correlation between the pustules and the grade of inflammation. This would also explain why there was a significant correlation between the Munro's microabscesses and the pustules of Kogoj since both of the parameters represent an inflammatory infiltrate in the epidermis albeit at different levels.

There was a strong correlation between the inflammatory infiltrate and the grade of capillary proliferation. There was also a correlation between the epidermal hyperplasia and the grade of capillary proliferation at a slightly lower P value (P = 0.08). It is believed that Vascular Endothelial Growth Factor (VEGF) and interleukin-8 released from keratinocytes may contribute to the vascularization seen in psoriasis. [10] Our study also suggests that lymphocytes perhaps release angiogenic factors that induce capillary proliferation and dilatation.

A series of elegant experiments by Mor et al., [11] proved that T cells can synthesize and secrete VEGF. The role of angiogenesis is a damaging factor in retinitis due to T lymphocyte VEGF secretion has been established. [12] As an extension of this study, if the role of T lymphocytes in the production of VEGF in psoriasis can be established, it will further establish the central role of the inflammatory cells in the pathogenesis of psoriasis.

There was a strong correlation between the epidermal hyperplasia and the presence of parakeratosis. This is not surprising because both share a common pathogenesis i.e., - rapid proliferation of keratinocytes and their terminal differentiation which leads to aberrantly retain intact nuclei (parakeratosis) and increased thickness of the epidermis. Explanations for the correlation with inflammation and capillary proliferation have already been elucidated.

The above study is a simple one which merely analyses histopathology to elucidate the pathogenesis of the disease. However it throws up several valuable conclusions. Firstly, this study suggests that the immunopathogenesis of psoriasis is predominantly based on the inflammatory response. This is in consonance with other studies who have suggested that psoriasis is primarily a T lymphocyte based disease. [13],[14] Several treatment modalities are now based on this concept. [15] The role of epidermal proliferation in the stimulation of angiogenesis has also been elucidated. It is hoped that the future treatment modalities will focus on the central role of inflammatory cells in the pathogenesis of this enigmatic disease.

 
   References Top

1.Krueger JG, Bowcock A. Psoriasis pathophysiology: Current concepts of pathogenesis. Ann Rheum Dis 2005;64:S2ii30-6.  Back to cited text no. 1
    
2.Chaudhari U, Romano P, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: A randomized trial. Lancet 2001;357:1842-7.  Back to cited text no. 2
    
3.Bayliffe AI, Brigandi RA, Wilkins HJ, Levick MP. Emerging therapeutic targets in psoriasis. Curr Opin Pharmacol 2004;4:306-10.  Back to cited text no. 3
    
4.Bos JD, Hulsebosch HJ, Krieg SR, Bakker PM, Cormane RH. Immunocompetent cells in psoriasis. In situ immunophenotyping by monoclonal antibodies. Arch Dermatol Res 1983;275:181-9.  Back to cited text no. 4
    
5.Das RP, Jain AK, Ramesh V. Current concepts in the pathogenesis of psoriasis. Indian J Dermatol 2009;54:7-12.  Back to cited text no. 5
[PUBMED]  Medknow Journal  
6.Ortonne JP. Recent developments in the understanding of the pathogenesis of psoriasis. Br J Dermatol 1999;140:1-7.  Back to cited text no. 6
    
7.Bos JD, De Rie MA. The pathogenesis of psoriasis: Immunological facts and speculations. Immunol Today 1999;20:40-6.  Back to cited text no. 7
    
8.Chang EY, Hammerberg C, Fisher G, Baadsgaard O, Ellis CN, Voorhees JJ, et al. T cell activation is potentiated by cytokines released by lesional psoriatic, but not normal, epidermis. Arch Dermatol 1992;128:1479-85.  Back to cited text no. 8
    
9.Smyth MJ, Zachariae CO, Norihisa Y, Ortaldo JR, Hishinuma A, Matsushima K. IL-8 gene expression and production in human peripheral blood lymphocyte subsets. J Immunol 1950;146:3815-23.  Back to cited text no. 9
    
10.Simonetti O, Lucarini G, Goteri G, Zizzi A, Biagini G, Lo Muzio L, et al. VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: Results of an immunohistochemical study. Int J Immunopathol Pharmacol 2006;19:751-60.  Back to cited text no. 10
    
11.Mor F, Quintana FJ, Cohen IR. Angiogenesis-inflammation cross-talk: Vascular endothelial growth factor is secreted by activated T cells and induces Th1 polarization. J Immunol 2004;172:4618-23.  Back to cited text no. 11
    
12.Vinores SA, Chan CC, Vinores MA, Matteson DM, Chen YS, Klein DA, et al. Increased vascular endothelial growth factor (VEGF) and transforming growth factor (TGF β) in experimental autoimmune uveoretinitis: Upregulation of VEGF without neovascularization. J Neuroimmunol 1998;89:43.  Back to cited text no. 12
    
13.Christophers E. The immunopathology of psoriasis. Int Arch Allergy Immunol 1996;110:199-206.  Back to cited text no. 13
    
14.Schön MP, Boehncke WH. Psoriasis. N Engl J Med 2005;352:1899-912.  Back to cited text no. 14
    
15.Krueger GG, Callis KP. Development and use of alefacept to treat psoriasis. J Am Acad Dermatol 2003;49:S87-97.  Back to cited text no. 15
    

What is new? 1. This article brings out the correlations between various histopathological parameters involved in the pathogenesis of psoriasis, which has not been elucidated well in literature previously. 2. The inflammatory infiltrate is central to the pathogenesis of psoriasis. 3. There is significant correlation between epidermal hyperplasia and capillary proliferation with inflammatory infiltrate in psoriasis.


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1]



 

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