From speaking to our community of practitioners, we learnt that many of you wanted a handy reference guide that summarises advanced testing options for health conditions.

In light of this, our Clinical Support Specialist, Virginia Blake, has written a clinically robust introduction to advanced testing options for psoriasis.

Read and refer to the below if ever you are looking for a starting point for advanced testing options for psoriasis.

What is this article about?

When working with skin conditions, understanding the disease mechanism is essential for deciding on which functional test to use and subsequent interventions.

This article looks at antecedents (risk factors), triggers and mediators for psoriasis as well as provide an overview of the advanced functional testing options avaliable for it.

Article objectives:

To classify psoriasis
To summarise psoriasis' key disease mechanisms
To provide a summary of the advanced functional tests avaliable to practitioners to assess and manage psoriasis

Psoriasis classification

Psoriasis is a chronic, inflammatory disease. In this condition, there is abnormal differentiation and proliferation of keratinocytes. Usually, skin would regenerate monthly, in psoriasis it occurs every 3-4 days. This leaves the skin red and inflamed, visibly raised and scaly. This occurs in patches and these patches can be three times thicker than the surrounding skin surface, described as acanthosis. The rate of skin replication here can be up to 1000 times faster than unaffected skin.

Psoriasis is associated with cardiovascular diseases, gastrointestinal issues, metabolic syndrome, infections, mental health issues and some cancers (ten Bergen et al., 2020) and with ulcerative colitis, Crohn’s disease and non-alcoholic fatty liver disease (NAFLD) (Fiorino & Omedei 2015).

Disease mechanism / aetiology

Precise aetiology is uncertain but the following factors are relevant:

Genetic factors

Family history of psoriasis is common among those with the disease. Surveying 1376 patients with psoriasis, an Italian study showed 46% had a relative with psoriasis (Altobelli et al., 2007).

Defects in cellular proliferation

A reduction in cyclic adenosine monophosphate (cAMP) is seen in the epidermal layer in psoriasis. cAMP and cyclic guanosine monophosphate (cGMP) are second messengers that regulate the activity of protein kinase A (PKA) and protein kinase G (PKG).

A lack of cAMP can increase PKA activity and this results in increased keratinocyte proliferation. The lack of cAMP also increases inflammation of the epidermis. Combined, this leaves the skin susceptible to plaque formation.

The immune system

There is some debate about autoimmunity in psoriasis. Research is ongoing and whether psoriasis is an autoimmune disease driven by autoantigen- specific T-cells or autoinflammation triggered by a genetically susceptible, overactive innate immune response to environmental factors is still debated (Fry et al., 2014; ten Bergen et al., 2020).

However, there is increasing evidence that there are autoimmune mechanisms AND defined cellular targets (Lande et al., 2014). Recent research has identified four psoriasis autoantigens: cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D (part of the phospholipase A2 enzyme family) and keratin 17 (ten Bergen et al., 2020).

LL-37 is an antimicrobial peptide, it can be produced by immune cells (neutrophils, antigen-presenting cells and mast cells) and skin cells (keratinocytes) when the skin is injured or there is bacterial or viral infection. In psoriasis, this may be overactivated.
ADAMTSL5 is secreted by melanocytes, and may catalyse the formation of microfibril in the extra cellular matrix and is a potential autoantigen target. Mast cells in psoriasis are a considerable source of PLA2G4D. This can generate neolipid antigens recognized by Langerhans cells. This can activate lipid‐specific T cells.
Keratin 17 may be targeted as a result of streptococcal molecular mimicry.

What is agreed is that it is a multifactorial disorder caused by the interaction of susceptible alleles and the environment.

The digestive system

There are a number of factors that may contribute to changes and imbalances between cAMP and cGMP. These include incomplete digestion of protein, bowel toxaemia and reduced liver function. An imbalance in cAMP and cGMP is typical when there is incomplete digestion of protein and reduced absorption (Raker et al. 2016).

Toxic products of intestinal yeasts and dysbiotic bacteria raises cGMP, which increases cellular proliferation (Pizzorno & Murray, 2021; Ojetti et al. 2006).

In case reports, Ely (2018) has identified increased intestinal permeability and an association with SIBO, H. pylori and Blastocystis hominis.

Gut-derived bacterial DNA has been found in psoriatic blood. The species identified were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, Streptococcus pyogenes, and Shigella fresneli . These are associated with increased levels of inflammatory IL-1β, IL-6, IL-12, tumor necrosis factor-α, and interferon γ. (Ramirez Bosca et al. 2015)

As yet, we don’t have robust data demonstrating that the accumulation of these toxins and their impact on liver function contribute to or worsen psoriatic symptoms. In practice, addressing these issues can improve outcomes.

Other factors

Stress, low sunshine, smoking, cold weather, streptococcal infections, gluten sensitivity, viral infections, alcohol all contribute (Alidrisi et al. 2019; Naldi, 2016; Fasano et al., 2015; Nair et al. 2014).

Medications that are associated with onset/ relapse include Beta blockers, ACE inhibitors, NSAIDs, Lithium chloroquine and interferon-α (Robert S. Porter & Justin L. Kaplan, 2019).

Rates are 8 times higher in inflammatory bowel disease (IBD) (Fiorino & Omedei 2015). There is an association with ulcerative colitis, Crohn’s disease and non-alcoholic fatty liver disease (NAFLD) (Fiorino & Omedei 2015).

Recommended advanced functional testing

Looking at the proposed mechanisms of disease and associated risk factors, there are some key areas to focus on:

Digestive Health
Detoxification and Environmental Toxins
Immune Activation
Allergy and Food Sensitivity

Tests can be prioritised based on symptoms. As there is growing evidence on the link between the microbiome and psoriasis, testing digestive health is a good place to start.

Digestive Health

GI360 Complete

This test is particularly useful in psoriasis as it can identify potential bacteria linked with psoriasis. These include Escherichia coli (by PCR and culture) , Klebsiella pneumoniae (by culture) , Enterococcus faecalis (by culture) , Proteus mirabilis (by culture) , Streptococcus pyogenes, and Shigella fresneli (by culture). It also has the gold standard of microscopy for parasites, Blastocystis hominis has been linked with psoriasis as well. With your results you will be able to target your intervention to the particular microbiology picture. The stool chemistries will assist you in deciding if extra digestive support around pancreatic enzymes or gall bladder function are required.

For psoriasis, I would recommend adding on H.Pylori to the GI360 for a comprehensive picture of potential gut pathogens.

H.Pylori. Add On

For psoriasis, I would recommend adding on H.Pylori to the GI360 for a comprehensive picture of potential gut pathogens.

Comprehensive Stool Analysis with PCR+ Parasitology

This includes various smaller panels for retesting specific areas of concern

SIBO Glucose

Hydrogen, methane, and combined gases to assess small intestinal bacterial overgrowth using glucose substrate

Buy the SIBO Gluculose as a practitioner

SIBO Lactulose

Hydrogen, methane, and combined gases to assess small intestinal bacterial overgrowth using lactulose substrate

Buy the SIBO Lactulose as a practitioner

Advanced Intestinal Barrier Assessment

Intestinal permeability has been suggested as a root cause of autoimmune diseases, systemic inflammation, and food sensitivities. This can be a contributing factor in psoriasis and increased intestinal permeability can lead to influx of toxins which may have an impact on hepatic function. This test assesses intestinal barrier function.

Organic Acid Test (OAT)

This is particularly relevant in psoriasis as it can give a broad picture of system health. Detoxification capacity is often affected in psoriasis. Microbial overgrowth may be a contributing factor. By examining the mitochondrial metabolites measured, the presence of excess toxins and toxicants can be deduced. There is high turnover of nutrients required for skin cell production, and you will find useful information on nutrient needs. I like this test as it is not too difficult for a client to do and gives a very broad picture of what is potentially going on for them. It is a great place to start if you are not sure where to begin.

Detoxification

Hepatic Detox Profile

An excellent tool for assessing phase 1 and 2 liver detoxification. This is useful in psoriasis as there is often an overload of toxins for processing. Establishing the rate of Phase 1 to Phase 2 is helpful for determining a safe detox protocol.

GPL-Tox

Environmental chemicals may be implicated in the pathogenesis of psoriasis or they may make it harder to improve symptoms with your protocol. This test examines the 172 most common and most deleterious to health environmental pollutants. This test is useful when you are not certain where toxicant exposure comes from. It can show up very interesting results in countryside dwellers and golfers.

MycoToxin

Mycotoxins have not been widely studied in relation to psoriasis although they can induce dermal toxicity in rodents (Doi & Uetsuka, 2014). Mycotoxins can impact the immune system negatively and can be a missing link in a chronic health condition. It is worth doing as part of the Envirotox Complete Panel. See below. This is an excellent value package of 4 tests for the price of less than 2.

ENVIROtox Complete Panel

Combines Organic Acid Test (OAT), GPL-Tox, Mycotoxins and Glyphosate for a comprehensive environmental toxicity assessment.

Toxic metals may increase oxidative stress, which may be a contributor to pathological inflammation in psoriasis. (Wacewicz-Muczyńska et al., 2021).

Mercury Tri Test

Assesses the body’s mercury overall burden and ability to detoxify and eliminate mercury.

Buy the ENVIROtox Complete Panel as a practitioner

Blood Metals Panel

Screens for eight nutrient elements and seven toxic metals for indication of elevated exposure to toxic metals or imbalances of nutrient elements in whole blood.

Immune Status

Cyrex Laboratories

Regenerus is the UK, Ireland and Europe representative for Cyrex Laboratories.
Cyrex Labs offer 18 arrays using their proprietary, patented laboratory techniques.

Popular panels include, but are not limited to:

Array 10 Foods, general
Array 3 Gluten
Array 4 Non-gluten Cross-reactive Foods and Dairy
Array 5 Multiple Autoimmune Reactivity Screen
Array 11 Chemical Immune Reactivity Screen
Array 12 Pathogen Associated Immune Reactivity
Array 14 Mucosal Immune Reactivity Screen (saliva)
Alzheimer’s LINX

Psoriasis has been linked with several autoimmune diseases including coeliac disease, Hashimoto’s and inflammatory bowel diseases. Array 5 would give information on any other potential autoimmune antibodies. Psoriasis is linked food sensitivity and eliminating trigger foods may improve the symptom picture, consider Array 3, 4 and 10.