REGENERUS: AN INTRODUCTION TO ADVANCED FUNCTIONAL TESTING FOR PSORIASIS

AN INTRODUCTION TO ADVANCED FUNCTIONAL TESTING FOR PSORIASIS

An introduction to advanced functional testing for psoriasis

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 available for it.

Article Objectives:

  • To classify psoriasis
  • To summarise psoriasis’ key disease mechanisms
  • To provide a summary of the advanced functional tests available 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

GI360 Complete is an advanced, innovative, comprehensive, and clinically applicable stool profile. Multiplex PCR molecular technology is used for microbiome abundance and diversity assessment via 45 key anaerobic bacteria, providing a dysbiosis index and diversity score along with functional markers relating to IBS and IBD risk. Growth-based culture and ID by MALDI-TOF (>1200 bacteria; >200 yeasts can be identified), sensitive biochemical assays and microscopy detect and assess the status of pathogens, viruses, parasites, and bacteria that may be contributing to acute or chronic gastrointestinal symptoms and disease.

GI360 Complete also includes a broad range of stool chemistry markers to assess digestion/absorption, inflammation, immunology, short-chain fatty acids, intestinal health markers, and beta-glucuronidase.

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.

Buy the GI360 Complete as a practitioner

H.Pylori. Add On

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

Buy the H.Pylori. Add On as a practitioner

Comprehensive Stool Analysis with PCR+ Parasitology

This includes various smaller panels for retesting specific areas of concern

Buy the Comprehensive Stool Analysis with PCR+ Parasitology as a practitioner

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

This test assesses intestinal barrier function, using a collection of innovative biomarkers (zonulin, DAO, histamine, DAO: Histamine ratio, and LPS antibodies IgA, IgM & IgG) to help clinicians determine if their patients have intestinal permeability, or “leaky gut”. 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 functions

Buy the Advanced Intestinal Barrier Assessment as a practitioner

Organic Acid Test (OAT)

An evaluation of 76 biomarkers provides a comprehensive metabolic snapshot of overall health, including intestinal microbial overgrowth (yeast and bacteria), mitochondrial health, neurotransmitter status, detox capacity, oxidative stress, markers for vitamin and mineral levels and oxalates.

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.

Buy the Organic Acid Test (OAT) as a practitioner

Detoxification

Hepatic Detox Profile

An excellent tool for assessing phase 1 and 2 liver detoxification via measurement of D-glucaric acid and mercapturic acids, respectively.

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.

Buy the Hepatic Detox Profile as a practitioner 

GPL-Tox

Provides assessment of exposure to 172 environmental pollutants and includes a marker for mutations of mitochondrial DNA.

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.

Buy the GPL-Tox (Toxic Organic Chemical Exposure) as a practitioner 

MycoToxin

Screens for seven mycotoxins and four mould species via LC-MS/MS

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.

Buy the MycoToxin as a practitioner

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).

Buy the ENVIROtox Complete Panel as a practitioner 

Mercury Tri Test

Assesses the body’s mercury overall burden and ability to detoxify and eliminate mercury. Unique in that it measures blood amounts and assesses excretion via hair and urine to give clear information on load and ability to excrete. Measures organic and inorganic 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.

Buy the Blood Metals Panel as a practitioner

Immune Status

Cyrex Laboratories

Regenerus is the UK, Ireland and Europe representative for Cyrex Laboratories.
Cyrex is a clinical immunology laboratory specialising in functional immunology and autoimmunity. They focus on assessing, understanding, and educating practitioners on environmentally induced autoimmunity. 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.

Buy the Cyrex panels as a practitioner 

Long Covid Panel / Autoimmune Trio Panel

Autoimmune diseases affect about 10% of the world’s population. Their induction is due to a combination of genetic predisposition and environmental factors that affect the functioning of the immune system through various mechanisms.
Among these environmental factors are infectious pathogens, which may not only assault and weaken the body and the immune system but could also induce autoimmunity through molecular mimicry between the pathogenic viruses and many human tissues.

This mimicry could cause an immune reaction in which antibodies produced against viral antigens may also attack the body’s own tissues. Subsequent viral infections are thought to cause exacerbation of the disease by further activating the immune response against viral and self-antigens.
 Three viruses, in particular, have been identified as the major players and contributors to inflammation and autoimmune disorders: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6).
Autoimmune Viral Trio panel detects the possible role of three viruses in a variety of inflammatory and autoimmune disorders, including Long COVID,
SARS-CoV-2, Epstein-Barr Virus and Human Herpes Type 6. Buy the Long Covid Panel as a practitioner

Allergy and Food Sensitivity

Food sensitivity is linked with psoriasis. The following tests may help identify trigger foods:

P88 Dietary Antigen Test

The P88 Dietary Antigen Test measures IgE, IgG4, IgG and complement (C3d) reactions to 88 commonly eaten foods.

This test analyses levels of IgE antibodies (the most known food allergy response) for 88 different food antigens. It also measures IgG4, a subclass of IgG, indicative of immune tolerance as IgG4 can block IgE antibodies from binding to receptor sites and releasing histamine.

P88 also measures IgG antibodies which mediate delayed allergic response with immune complexes. Within an immune complex, the complement component 3 (C3) is converted into C3d, an activator of the complement cascade. Complement activation is well-defined in the research as one of the most potent causes of inflammatory food reactions. P88 Dietary Antigen test is unique in that it detects multiple classes of IgG (types I, II, III and IV) and complement, resulting in a higher sensitivity.

Buy the Dietary Antigen Test as a practitioner 

Cyrex Laboratories

Regenerus is the UK, Ireland and Europe representative for Cyrex Laboratories. Cyrex is a clinical immunology laboratory specialising in functional immunology and autoimmunity. They focus on assessing, understanding, and educating practitioners on environmentally induced autoimmunity. Cyrex Labs offer 18 arrays using their proprietary, patented laboratory techniques.

Food sensitivity panels:

  • Array 10 Foods, general
  • Array 3 Gluten
  • Array 4 Non-gluten Cross-reactive Foods and Dairy

Buy the Cyrex panels as a practitioner

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