From speaking with our community of practitioners, we learnt that many wanted handy reference guides to summarise advanced testing options for key health conditions.
In light of this, our Clinical Support Specialist, Virginia Blake, has written a clinically robust introduction to advanced testing options for Lichen Planus.
Read and bookmark this page if you are ever looking for a starting point for advanced testing options for Lichen Planus.
What is this article about?
In this article, I'll take a look at Lichen Planus; examining the risk factors, aetiology and pathology and how it can inform test selection. There is less research available that is relevant to nutritional therapy than in psoriasis, but some useful insights can be inferred from the current thinking on aetiology.
- To classify Lichen Planus
- To summarise Lichen Planus' key disease mechanisms
- To provide a summary of the advanced functional tests available to practitioners to assess and manage Lichen Planus
Lichen Planus Classification
Lichen Planus is a chronic, inflammatory, and/or autoimmune disease that affects the skin, oral mucosa, genital mucosa, scalp, and nails. On the skin, it presents as a purplish itchy, flat bumps. In the mouth and vagina and other mucous membranes, it forms white patches with or without painful sores.
Oral lichen planus (OLP) increases the risk of oral cancer. Genital lichen planus can cause significant pain and may leave scars, with sexual dysfunction being a potential long term complication. (Li et al., 2021).
The skin lesions in lichen planus are described using the six P's (planar, purple, polygonal, pruritic, papules, plaques). The diagnosis is usually based on clinical signs but 4mm punch biopsy can be useful (Kordova et al. 2013). Incidence of oral lichen planus (OLP) is 2-5% of population, predominantly found in middle aged women. (Nosratzehi, 2018), while genital lichen planus (GLP) affects 0.5-1% of the general population with the middle aged being most commonly affected (Khurana et al., 2019).
Disease mechanism / aetiology
Exact aetiology has not yet been determined. The current most likely theory is that it is immune-related and mediated by cyto-toxic T cells, which target basilar keratinocytes. Why this reaction is triggered is not yet known but there is likely to be genetic predisposition. Gene polymorphisms studied in relation to lichen planus include HLA‐A3, HLA‐DR1, HLA‐DRB1*0101, HLA‐DQ1, and HLA‐DQB1*0201 (Bermejo-Fenoll & López-Jornet, 2006).
Is it autoimmune?
Like psoriasis, definitive autoantibodies have not been established in lichen planus. (Kharkar et al., 2018).
Around 61% of patients with erosive vulval LP show antibodies which are anti-basement membrane. These may be important in disease progression but may be transient and not the initial pathogenic trigger (Khuruna et al. 2019)
In a cross-sectional epidemiological study of 100 lichen planus patients in Mumbai, 65% of patients tested positive for one of 6 antibodies assessed, while 35% showed none of the 6 tested antibodies. The antibodies measured and the incidence are below:
- Anti-keratinocyte antibody in 26%
- Anti-nuclear antibody in 22%
- Anti-desmoglein 1 antibody in 19%
- Anti-desmoglein 3 antibody in 16%
- Anti-mitochondrial antibody in 9%
- Anti-thyroglobulin antibody in 6% patients (Kharkar et al., 2018).
Incidence of autoantibodies in a healthy/ pre-clinical population can be 23.6% (Haller-Kikkatalo et al., 2017), so these antibody findings are significant.
Other Factors to Consider
OLP is associated with Hepatitis C but this has not been found in GLP to date (Khuruna et al., 2019).
It is known that stressful events can worsen OLP. In a meta-analysis of 10 studies with control groups (269 with OLP v 268 control) cortisol levels were found to be significantly higher in patients with OLP compared with control groups. (Lopez-Jornet et al., 2019)
In a literature review of 58 studies of patients with OLP, lower levels of the following micronutrients were found: iron, zinc, calcium, vitamin D, vitamin B12, folic acid, and antioxidants such as vitamins C and E. Iron storage and use was also affected with lower levels of haemoglobin and ferritin and raised total iron binding capacity (Gholizadeh & Sheykhbahaei, 2020).
There is a significant association between high homocysteine and OLP, with some research suggesting a correlation of high blood homocysteine with severity of OLP (Chen et al., 2015). Also in OLP; increased levels of peroxidation marker 8-Hydroxydeoxyguanosine (8-OHDG) have been found compared with healthy controls (Rai et al., 2010).
Oral Microbiome and OLP
Oral dysbiosis may contribute to pathogenesis in OLP, and H. Pylori has been found to have a significant correlation with development of erosive OLP (Li et al., 2021).
Genital and Gut Microbiome and Lichen Planus
There is limited research on the impact of the vaginal microbiome on either aetiology or progression of OLP. I did come across a few case reports that described treating UTI infections with metronidazole resolved GLP. (Shelley & Shelley, 1984) (Wahba-Yahav, 1995)
The research is on lichen planus and the gut microbiome is extremely limited. In a systematic review with primary focus on vaginal microbiome differences in healthy versus (pre)malignant vulvar disease did find associations with higher abundance of Peptostreptococcus anaerobius and Prevotella melaninogenica and lower abundance of Streptococcus angionosuscompared to healthy controls in vaginal and faecal samples (Pagan et al., 2021).
Infections and Lichen Planus
A recent systematic review and meta-analysis of 10 studies with 386 OLP cases and 304 controls has concluded that Epstein Barr virus (EBV) infection shows a statistically significant association with OLP. The recommendation is further research to determine the potential role of EBV in OLP pathogenesis. (Ashraf et al., 2020)
Other Potential Triggers
- Flu vaccine
- Certain pigments, chemicals and metals
- Pain relievers, such as ibuprofen (Advil, Motrin IB, others) and naproxen (Aleve, others)
- Certain medications for heart disease, high blood pressure or arthritis
- (Hammouda and Martin, 2015)
Recommended Advanced Testing for Lichen Planus
As is typical in nutritional therapy, we are looking at pre-clinical research to inform our clinical practice. We are faced with a real life person with a condition that nutrition and lifestyle interventions will most likely help, but with limited evidence to support our interventions. Based on a review of the current evidence on proposed mechanism of disease and associated risk factors, my clinical experience with this condition and what fits with each client’s symptoms, unique history and willingness to participate, I suggest the following tests may be of benefit for directing interventions:
- Gut and vaginal microbiome
- Detoxification and Environmental Toxins
- Immune Activation
- Endocrine / Stress
Taking the unique picture your client presents, testing can be prioritised based on symptoms. I will start with general overview tests, which can be helpful when initially working up the case.
General Overview Advanced Tests
Functional Platinum Panel by Medical Diagnosis
The Functional Platinum Panel provides a comprehensive insight into these key health areas: full blood count, biochemistry, endocrinology, haematology, and immunology.
This an excellent all-round test; alongside areas listed above, it also assesses vitamin B12, calcium, iron including ferritin and TIBC, folate and homocysteine. Thyroperoxidase and thyroglobulin antibodies are included.
Organic Acid Test (OAT) by Great Plains Laboratory
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 another big picture test, particularly relevant in Lichen Planus as it can give a broad picture of system health. Detoxification capacity may be affected in lichen planus. 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.
The Gut and Vaginal Microbiome
GI360 Complete Add on H.Pylori. by Doctor’s Data
Although the research is limited, there are indications that the gut microbiome is altered in both OLP and GLP. If we think about lichen planus as a potential autoimmune disease, we have evidence from other autoimmune conditions that changes in the microbiome can affect disease progression.
I would highly recommend the WomensKey and MensKey Complete in GLP. As mentioned above, research is limited, but in practice, identifying and resolving chronic infection may improve symptom picture and disease progression. See test descriptions below.
Urokey by Microgen Dx
UroKey uses state-of-the-art technology (qPCR+NGS Next Generation Sequencing) to provide actionable diagnostics that can end the frustration and pain of chronically infected UTIs.
WomensKey Complete by MicrogenDx
As Urokey mentioned above, with additional assessment of the vaginal microbiome. To help understand contributing factors to chronic UTIS, Interstitial Cystitis, Bacterial Vaginosis and recurrent yeast infections.
MensKey Complete by Microgen Dx
As Urokey mentioned above, with additional assessment of the seminal microbiome contributing to chronically infected UTIs, Prostatitis and Epididymitis.
Autoimmune Trio / Long Covid Panel by Immunosciences Lab
Assesses main viruses associated with triggering/ mediating autoimmune or autoinflammatory illness.
Hepatic Detox Profile by Doctor’s Data
An excellent tool for assessing phase 1 and 2 liver detoxification via measurement of D-glucaric acid and mercapturic acids, respectively.
GPL-Tox by Great Plains Laboratory
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 lichen planus 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 by Great Plains Laboratory
Screens for seven mycotoxins and four mould species via LC-MS/MS.
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.
Enviro-Tox Complete Panel by Great Plains Laboratory
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 lichen planus. (Wacewicz-Muczyńska et al., 2021)
Mercury Tri Test by Quicksilver Scientific
Assesses the body’s mercury overall burden and ability to detoxify and eliminate mercury.
Blood Metals Panel by Quicksilver Scientific
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.
Regenerus is the UK, Ireland and Europe representative for Cyrex Laboratories.
Cyrex is a clinical immunology laboratory specialising in functional immunology and 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
There is a greater incidence of autoantibodies in Lichen Planus, array 5 tests for 24 specific autoantibodies. is linked food sensitivity and eliminating trigger foods may improve the symptom picture, consider Array 3, 4 and 10.
Allergy and Food Sensitivity
This is not particularly well researched in lichen planus but there are small studies linking coeliac disease with lichen planus and case reports of symptoms improving on gluten free diets (Khan et al., 2020).
P88 Dietary Antigen Test by Precision Point Diagnostics
The P88 Dietary Antigen Test measures IgE, IgG4, IgG and complement (C3d) reactions to 88 commonly eaten foods.
Food sensitivity panels:
- Array 10 Foods, general
- Array 3 Gluten
- Array 4 Non-gluten Cross-reactive Foods and Dairy
DUTCH Complete by Doctor's Data
There is convincing evidence of the link between stress and onset/ worsening of lichen planus. The DUTCH tests listed below look at cortisol metabolism and also include the marker 8OH-DG, raised levels of which are associated with lichen planus. The DUTCH plus and Complete include markers of B6 and B12.
DUTCH Plus by Precision Analytical
As DUTCH Complete above, with additional assessment of the cortisol awakening response (CAR) which can be used to evaluate HPA-axis function further.
DUTCH Cycle Mapping with Complete or Plus by Precision Analytical
DUTCH Cycle Mapping, Sex Hormone Metabolism and Adrenal Metabolism are also available as standalone tests.
NeuroBasic Profile by Doctor’s Data
NeuroBasic Profile is a non-invasive urinary profile to assess the body's ability to make and break down neurotransmitters (Dopamine, Serotonin, 5HIAA, GABA, Glutamate, Glycine, Epi, NorEpi, Epi: NorEPi ratio, Histamine, PEA) and is representative of the whole body's neurotransmitter levels.
Comprehensive Neurotransmitter Profile by Doctor’s Data
This extension of the NeuroBasic provides a more detailed assessment of neurotransmitter function and includes metabolites to help understand nutritional cofactor need and expression of nutrigenetics.
NeuroBasic or Comprehensive Neurotransmitter Profile work well with hormone testing and can be ordered as an add-on to HuMap panels at a reduced cost.
Essential Vitamin Profile by Lab4More
Low levels of iron, calcium vitamin E, B12 and folic acid have been found in lichen planus. Zinc is required for skin integrity and selenium has vital roles in endogenous antioxidant production. This test can help you devise your micronutrient supplement plan.
Ashraf, S., Al‐Maweri, S. A., Alaizari, N., Umair, A., Ariffin, Z., Alhajj, M. N., Kassim, S., & Awan, K. H. (2020). The association between epstein‐barr virus and oral Lichen Planus: A systematic review and meta‐analysis. Journal of Oral Pathology & Medicine, 49(10), 969–976.
Bermejo-Fenoll, A., & López-Jornet, P. (2006). Familial oral lichen planus: presentation of six families. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 102(2), e12–e15.
Bravo, D., Hoare, A., Soto, C., Valenzuela, M. A., & Quest, A. F. G. (2018). Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World Journal of Gastroenterology, 24(28), 3071–3089.
Ceovic, R., Mance, M., Bukvic Mokos, Z., Svetec, M., Kostovic, K., & Stulhofer Buzina, D. (2013). Psoriasis: Female Skin Changes in Various Hormonal Stages throughout Life—Puberty, Pregnancy, and Menopause. BioMed Research International, 2013, 1–6.
Chen, H.-M., Wang, Y.-P., Chang, J. Y.-F., Wu, Y.-C., Cheng, S.-J., & Sun, A. (2015). Significant association of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homocysteine level with oral lichen planus. Journal of the Formosan Medical Association, 114(2), 124–129.
Haller-Kikkatalo, K., Alnek, K., Metspalu, A., Mihailov, E., Metsküla, K., Kisand, K., Pisarev, H., Salumets, A., & Uibo, R. (2017). Demographic associations for autoantibodies in disease-free individuals of a European population. Scientific Reports, 7(1).
Karatasli, B., Karatasli, G., Mete, O., Erdem, M. A., & Cankaya, A. B. (2018). Healing of Oral Lichenoid Lesions following Replacement of Dental Amalgam Restorations with Feldspathic Ceramic Inlay-Onlay Restorations: Clinical Results of a Follow-Up Period Varied from Three Months up to Five Years. BioMed Research International, 2018, 1–7.
Kharkar, V., Rambhia, K. D., Pradhan, V., Patwardhan, M., Ghosh, K., & Khopkar, U. S. (2018). A study of prevalence of autoantibodies in patients with lichen planus from Mumbai, India. Indian Journal of Dermatology, Venereology and Leprology, 84(6), 667.
Li, S., Zhang, Y., Yang, Z., Li, J., Li, Y., Li, H., Li, W., Jia, J., Ge, S., & Sun, Y. (2021). Helicobacter pylori infection is correlated with the incidence of erosive oral lichen planus and the alteration of the oral microbiome composition. BMC Microbiology, 21(1).
Lopez-Jornet, P., Zavattaro, E., Mozaffari, H. R., Ramezani, M., & Sadeghi, M. (2019). Evaluation of the Salivary Level of Cortisol in Patients with Oral Lichen Planus: A Meta-Analysis. Medicina, 55(5), 213.
Mehrbani, S. P., Motahari, P., Azar, F. P., & Ahari, M. A. (2020). Role of interleukin-4 in pathogenesis of oral lichen planus: A systematic review. Medicina Oral Patología Oral y Cirugia Bucal, e410–e415. https://doi.org/10.4317/medoral.23460
Nair, S., Faizuddin, M., & Dharmapalan, J. (2014). Role of Autoimmune Responses in Periodontal Disease. Autoimmune Diseases, 2014, 1–7.
Pagan, L., Ederveen, R. A., Huisman, B. W., Schoones, J. W., Zwittink, R. D., Schuren, F. H., Rissmann, R., Piek, J. M., & van Poelgeest, M. I. (2021). The human vulvar microbiome: A systematic review. Microorganisms, 9(12), 2568.
Rai, B., Kaur, J., Jacobs, R., & Singh, J. (2010). Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. Journal of Oral Science, 52(2), 251–256.