According to MIT view, PSORIASIS is caused by ‘off-target’ actions of antibodies generated in the body against various ‘alien proteins’ such as infectious agents of ITCH. As such, it is a MIASMATIC disease belonging to the PSORA. When these antibodies attack the cells of skin, misinterpreting them as pathogenic antigens, a series of biochemical process set in, resulting in inflammatory changes and hyperkaratinization of epidermal layers amounting to a state of PSORIASIS.
According to ‘immunological’ view proposed by modern researchers, psoriasis develops when the immune system mistakes a normal skin cell for a pathogenic agent, and sends out faulty signals that cause overproduction of new skin cells that appear as psoriatic lesions. This model also broadly fits to the MIT ‘miasmatic’ model, only difference being that ‘immunological model’ does not mention about the role of ‘antibodies’ formed against previous infections.
Other than skin, psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. This similar to the arthritis produced by antibodies of streptococcus throat infections. Between 10% and 30% of all people with psoriasis also has psoriatic arthritis.
The cause of psoriasis and its molecular level pathology is not fully understood yet. Over and above immunological or miasmatic aspects, it is believed to have a genetic component also, and ‘genetic expressions’ leading to local psoriatic changes can be triggered by an injury to the skin, thereby attracting ‘mismatic’ antibodies into dermal cells.
Various environmental factors have been suggested as aggravating to psoriasis, including oxidative stress, mental stress, withdrawal of systemic corticosteroids, as well as exposure to various other environmental factors such as chemicals. All these factors create a favorable environment for the attack of dermal cells- keratinocytes’ by ‘miasmatic’ antibodies.
Existing hypothesis is that the disease as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system. T cells -which normally help protect the body against infection- become active, migrate to the dermis and trigger the release of cytokines such as tumor necrosis factor-alpha TNFα, which cause inflammation and the rapid production of skin cells. It is not yet clearly known what initiates the activation of the T cells. Antibodies generated against various alien proteins such as infectious agents entering the body may play such a role, through their off-target actions.
This immune-mediated or miasmatic model of psoriasis has been supported by the observation that various immunosuppressant medications can clear psoriasis plaques. However, the role of the immune system is not fully understood, and it has recently been reported that an animal model of psoriasis can be triggered in mice lacking T cells. Animal models, however, reveal only a few aspects resembling human psoriasis. Compromised skin barrier function has a role in psoriasis susceptibility.
Psoriasis is considered as a fairly idiosyncratic disease, since majority of cases of psoriasis may worsen or improve without any apparent reason. Studies of the factors associated with psoriasis tend to be based on small, samples of individuals belonging to hospital samples. These studies tend to suffer from representative issues, and an inability to tease out causal associations in the face of other unknown intervening factors. Conflicting findings are often reported in such studies. Nevertheless, the first outbreak is sometimes reported following a mental or physical stress, skin injury, and streptococcal infections, which attract ‘immune bodies’ to attack the certain skin cells, by mistaking them as pathogenic agents. Conditions that have been reported as accompanying a worsening of the disease also include infections, stress, and changes in season and climate. Certain medicines, including lithium salt, beta blockers and the antimalarial drug chloroquine have been reported to trigger or aggravate the disease.
Excessive alcohol consumption, smoking and obesity may exacerbate psoriasis or make the management of the condition difficult or perhaps these co-morbidities are effects rather than causes. Hairsprays, some face creams and hand lotions, are also considered to cause an outbreak of psoriasis. In 1975, Stefania Jablonska and collaborators advanced a new theory that special antibodies tend to break through into the lower layers of the skin and set up a complex series of chemical reactions, which comes very close to MIT interpretation of miasms as ‘off target actions’ of antibodies.
Psoriasis occurs more likely in dry skin than oily or well-moisturized skin, and specifically after an external skin injury such as a scratch or cut , which is known as Koebner phenomenon. This is believed to be caused by an infection, in which the infecting organism thrives under dry skin conditions with minimal skin oil, which otherwise protects skin from infections. The case for psoriasis is opposite to the case of athlete’s foot, which occurs because of a fungus infection under wet conditions as opposed to dry in psoriasis. This infection induces inflammation, which causes the symptoms commonly associated with psoriasis, such as itching and rapid skin turnover, and leads to drier skin, as the infecting organism absorbs the moisture that would otherwise go to the skin. All these observations authenticate the role ‘miasmatic’ antibodies producing ‘off-target’ inhibitions in certain biochemical process in skin cells, resulting in PSORIASIS.
Psoriasis has a large hereditary component, and many genes are associated with it, but it is not clear how those genes work together. Most of them involve the immune system, particularly the major histo-compatibility complex (MHC) and T cells. The main value of genetic studies is they identify molecular mechanisms and pathways for further study and potential drug targets.
Classic genome-wide linkage analysis has identified nine locations on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes. Many of those genes are on pathways that lead to inflammation. Certain variations or mutations of those genes are commonly found in psoriasis.
The major determinant is PSORS1, which probably accounts for 35–50% of its heritability. It controls genes that affect the immune system or encode proteins that are found in the skin in greater amounts in psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes a MHC class I protein; CCHCR1, variant WWC, which encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSM, variant allele 5, which encodes corneodesmosin, which is expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.
Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.
Two major genes under investigation are IL12B on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. T cells are involved in the inflammatory process that leads to psoriasis.
These genes are on the pathway that ends up upregulating tumor necrosis factor-α and nuclear factor κB, two genes that are involved in inflammation.
Recently the first gene directly linked to psoriasis has been identified. Studies have suggested that a rare mutation in the gene encoding for the CARD14 protein plus an environmental trigger was enough to cause plaque psoriasis, which is the most common form of psoriasis.
In psoriasis, immune cells move from the dermis to the epidermis, where they stimulate skin cells or keratinocytes to proliferate. Psoriasis does not seem to be a true autoimmune disease. In an autoimmune disease, the immune system confuses an outside antigen with a normal body component, and attacks them both. But in psoriasis, the inflammation does not seem to be caused by outside antigens, although DNA does have an immunostimulatory effect. Researchers have identified many of the immune cells involved in psoriasis, and the chemical signals they send to each other to coordinate inflammation. At the end of this process, immune cells, such as dendritic cells and T cells, move from the dermis to the epidermis, secreting chemical signals, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6, which cause inflammation, and interleukin-22, which causes keratinocytes to proliferate.
The immune system consists of an innate immune system, and an adaptive immune system. In the innate system, immune cells have receptors that have evolved to target specific proteins and other antigens that are commonly found on pathogens. In the adaptive immune system, immune cells respond to proteins and other antigens that they may never have seen before, which are presented to them by other cells. The innate system often passes antigens on to the adaptive system. When the immune system makes a mistake, and identifies a healthy part of the body as a foreign antigen, the immune system attacks that protein, as it does in autoimmunity.
In psoriasis, DNA is an inflammatory stimulus. DNA stimulates the receptors on plasmacytoid dendritic cells, which produce interferon-α, an immune stimulatory signal (cytokine). In psoriasis, keratinocytes produce antimicrobial peptides. In response to dendritic cells and T cells, they also produce cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signals more inflammatory cells to arrive and produces further inflammation.
Dendritic cells bridge the innate and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells. Certain dendritic cells can produce tumor necrosis factor-α, which calls more immune cells and stimulates more inflammation. Targeted immunotherapy, and psoralen and ultraviolet A (PUVA) therapy, reduces the number of dendritic cells.
T cells move from the dermis into the epidermis. They are attracted to the epidermis by alpha-1 beta-1 integrin, a signalling molecule on the collagen in the epidermis. Psoriatic T cells secrete interferon-γ and interleukin-17. Interleukin-17 is also associated with interleukin-22. Interleukin-22 induces keratocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10.
All the factors detailed above strongly support the MIT model of PSORIASIS, according to which it is a disease caused by miasm of PSORA, or ‘off-target’ actions of antibodies generated in the body against various ‘alien proteins’ such as infectious agents of ITCH. Homeopathic treatment of psoriasis should be based on this perspective.