PSORIASIS-1

MECHANISM   OF   PSORIASIS?

📌INTRODUCTION:-

Psoriasis is a chronic, inflammatory and proliferative condition of the skin, associated with systemic manifestations in many organ systems. The most characteristic lesions consist of erythematous, scaly, sharply demarcated plaques, present particularly over the extensor surfaces and scalp. Both genetic and
environmental influences have a critical role in its aetiology and pathogenesis. There are many reports that psoriatic patients tend to have concurrent illnesses or comorbidities which worsens the disease burden. Patients with moderate to severe psoriasis are found to have a higher association with these extra
cutaneous disease manifestations.

📌HISTORY:-

The chronicle of psoriasis begins in ancient times when psoriasis, leprosy, and other
inflammatory skin disorders were thought to be the same condition.  Later we understood that psoriasis is totally a different entity.As Bechet expressed, “Psoriasis is an antidote for dermatologists’ ego”.Between 129 and 99 BC, the word “psora” was first used by Galen to describe a skin disorder characterized by a scaliness of the eyelids, corners of the eyes, and scrotum. Robert Willan(1809), the father of modern dermatology is credited with the first detailed clinical description of psoriasis(On Cutaneous Diseases, published in 1808) and hence it is also termed as “Willan’s Lepra.” 

 📌EPIDEMIOLOGY:-

📍AGE:-There are two peak ages of incidence, the first occurring between 16 and 22 years and the second peak between 57 and 62 years of age. The concept of early and late onset psoriasis was first introduced by Henseler and Christophers in 1985. 

📍GENDER:-Psoriasis affects both males and females, though some studies have reported an earlier age of onset in girls and severe disease more in men.Indian study by T.R Bedi showed a male predominance with a sex ratio of 2.4:1. Also,Dogra et al reported that it is twice more common in males compared to females.

📍RACIAL DIFFERENCES:- European populations had a higher prevalence than African and Asian populations .Prevalence is relatively less among Asians

📌WHY DO YOU GET PSORIASIS??

It is  due to a complex interaction between genetic,environmental and immunological factors.

Ι)GENETIC   FACTORS:-

There is an overwhelming evidence that psoriasis has an important genetic component.
According to family-based studies, an offspring of two affected parents has a 50% chance of developing psoriasis; this chance decreases to 16% if only one parent is affected. Also, if a child has psoriasis and neither parent has it, there is an 8% chance for that child's sibling to develop psoriasis . 

Earlier age of onset when the disease was inherited from the father, consistent
with ‘genetic anticipation' is also noted.

Examination of individuals from the Danish Twin Registry has shown a concordance of Psoriasis in 20% of monozygotic twins and 9% of
Dizygotic twins.

 The molecular genetic study showed at least nine chromosomal loci with
statistically significant evidence for linkage PSORS1 to PSORS9.

PSORS1 is located within MHC on chromosome 6p.Guttate Psoriasis is strongly associated with PSORS1.

 The penetrance of HLA-Cw6 was estimated to be only 10%, suggesting HLACw6 alone was insufficient to explain the disease genetics. PSORS2 on chromosome17q finally identified as CARD14 gene, and its mutation leads to activation of the NF-ḱβ pathway.

II. ENVIRONMENTAL   FACTORS

📍TRAUMA:-

Psoriasis can occur in sites of cutaneous trauma(koebner phenomenon or isomorphic response). The reported incidence of koebner response in psoriasis varies from 11% to 75%.Study by Boyd and Neldner showed that the latent period between injury to uninvolved skin and appearance of disease is usually 10-14 days, but it may range from 3 days to several years.Studies by Miller et al. and Thappa et al. confirmed that, the involuting central portion of the psoriatic plaque is refractory to the experimental induction of psoriasis and has been called “zone of immunite locale”. Boyd and Neldner showed that psoriasis following trauma occurs more frequently in winter than in summer .

 📍INFECTIONS:-

A study by Gudjonsson et al. showed that psoriasis can be triggered by streptococcal infection particularly guttate Psoriasis. HIV infection can also lead to exacerbation of psoriasis.Mcfadden et al. showed that many of the candidate genes linked to psoriasis are associated with the acquired or innate immune system, which is also important in host defence to invasive streptococcal infections. Psoriasis exacerbation has been linked with skin and/or gut colonization by Staphylococcus aureus, Malassezia and Candida albicans. 

📍DRUGS:-

Although a plethora of drugs has been implicated in provoking psoriasis, the
strongest evidence is for lithium, beta-blockers, antimalarials, non-steroidal antiinflammatory drugs and tetracyclines. In addition, angiotensin-converting enzyme inhibitors, interferons, digoxin, clonidine,carbamazepine, valproic acid, calciumchannel blockers, granulocyte-colony stimulating factor, potassium iodide, ampicillin, penicillin, progesterone, morphine and acetazolamide have been reported 

📍SUNLIGHT:-

 Sunlight is generally beneficial;But Schon and Boehncke reported that in 5-20% of the cases it may cause exacerbation,which maybe noted during summer

📍STRESS:- 

As studied by Blok et al. upto 80% of psoriatic patients reported that psychological
distress results in flare up of the disease. Moderate to severe psoriasis is associated with increased levels of depression anxiety and worry.  20% of them may require treatment with an anti-depressant. There is numerous anatomical and physiological connection between the nervous system and the skin known as the ‘neuro-cutaneous axis or Brain Skin axis. This include substance P,Calcitonin Gene Related Peptide, Nerve growth factor, and Corticotrophin Releasing Hormone. These neurotransmitters have immune modulatory property. This neuro immune cutaneous axis both triggers and maintains cutaneous inflammation in psoriasis.Evers et al. showed that stress results in altered hypothalamic-pituitary-axis activity with lowered serum cortisol levels and an increase in disease
activity.

📍SMOKING :-

The association of psoriasis and smoking has been evaluated in many studies. These studies found an association between smoking and incidence of psoriasis, with a possible dose-effect of smoking intensity and duration on psoriasis incidence. By these findings Armstrong et al. suggested that smoking is an independent risk factor for the development of psoriasis and that patients with established psoriasis  continue to smoke more than patients without psoriasis. Cigarette smoking is associated with exacerbation of palmoplantar pustulosis and a poor response to treatment. It modifies the expression of HLA-Cw6, HLADQ*0201, and CYP1A1 and is associated with stimulation of MAPK and NFκB.Also,it is proposed that proposed that nicotine may provoke psoriasis by neoangiogenesis and stimulation of neutrophil chemotaxis.

📍ALCOHOLISM:-

Alcohol consumption has been linked to psoriasis .Excessive alcohol intake exacerbates psoriasis due to alcohol abuse associated immune dysfunction, increased production of inflammatory cytokines, such as cyclin D1 and keratinocyte growth factor, and an increased susceptibility to superficial infections and trauma. Also,some studies suggest that alcoholism increases the risk for mortality among patients with psoriasis. 

📍 DIET:-

In a study by Wolters,diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies.Also, diets rich in Ω-3 polyunsaturated fatty acids from fish oil showed beneficial effects. All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile so that inflammatory processes are suppressed. Red meat  is not good in psoriasis



All the above mentioned factors contribute to the pathogenesis of psoriasis by increasing the inflammatory environment of the skin