Remission of long-standing livedoid vasculopathy using a whole foods plant-based diet with symptoms recurrent on re-challenge with standard Western diet
- 1 Plant Based New Zealand Health Trust, Gisborne, Gisborne, New Zealand
- 2 Three Rivers Medical, Gisborne, New Zealand
- 3 Tairawhiti District Health, Gisborne, New Zealand
- 4 Hauora Tairawhiti, Gisborne, New Zealand
- Correspondence to Morgen Smith; morgensm@gmail.com
Abstract
A 63-year-old woman presented with ulcerations of both lower legs. Symptom onset was 2006. In 2013 she saw a dermatologist and a biopsy suggested livedoid vasculopathy. In 2016 a whole food plant-based diet (WFPB) was advised as a potential treatment in the community setting. The patient changed her diet accordingly, but was not otherwise treated. The symptoms remitted completely with close adherence to the WFPB diet and recurred on multiple occasions associated with poor dietary adherence. There was a self-identified dose–response relationship with degree of adherence and number and intensity of flares. There were no known adverse side effects from the diet change, although the patient felt adherence to be difficult at times. The mechanism is not completely clear; we speculate that the dietary changes directly affect vascular endothelial health, which in turn affects propensity towards a prothrombotic state. More research is needed to elucidate potential mechanisms.
Background
Livedoid vasculopathy (LV) presents with 'exquisitely painful' ulcers from occluded ischaemic capillaries of the lower extremities. Ulcers are usually 4–6 mm in size, although they can be larger.1 The porcelain-white, painless and stellate-shaped scars that follow are called 'atrophie blanche'.2 Evidence of poor blood flow (cyanosis, levido reticularis, Raynaud’s phenomenon) is often present. Histopathology shows intraluminal thrombosis with immunofluorescence commonly showing C3, IgM, IgA, IgG and fibrin in the vessel wall.
This rare idiopathic condition affects one in 100 000 with a mean age of onset of 32 years and a female:male preponderance of 3:1.3 Livedoid vasculopathy “continues to baffle researchers and clinicians alike by its enigmatic pathogenesis”.1
There is no commonly accepted cure. Management options include anticoagulation, which has a high favourable response rate (defined as any degree of improvement), compression stockings (recommended if stasis is present) and smoking cessation. One case series found that 13% of all treatments led to adverse reactions and 44% of patients had received a treatment which was not tolerated.3
A search on Ovid and PubMed reveals no findings when searching Livedoid Vasculopathy AND diet OR nutrition therapy.
Case presentation
In March 2016 a 63-year-old woman working as a healthcare professional presented to her local medical clinic with a 1×2 cm ulcer on her lower left leg. Antibiotics had aided in healing of previously infected ulcers, and these were prescribed.
Her usual symptoms were sporadically itching red blotches on the lower legs and feet, swollen feet, which would form into painful oozing ulcerations varying from small (1–6 mm) to large (>10 mm). She had experienced ulcer outbreaks every few weeks to months since 2008, which could be precipitated by clothes rubbing or a minor injury. Symptoms were notably worse in the summertime.
The initial diagnosis was of non-specific capillaritis, made in 2006 following onset of symptoms a year previously. She avoided black stockings (due to dye) and avoided aspirin as per recommendations, but showed no improvement. She used compression stockings which helped to reduce ulcer formation and swelling; a single day without stockings would lead to more painful ulcerations. These cost the patient $400 per year.
The patient was bothered by the sores because they were 'unsightly' and therefore she only wore pants or long skirts. She was upset that the treatments failed to cure her condition despite high adherence; she had expected there would be something she could do.
From 2006 through to 2016 the patient was taking prescribed ibuprofen every night and occasionally codeine for severe pain. The patient was in otherwise good health and her only other medications in 2016 were pantoprazole 20 mg and citalopram 20 mg daily. No systemic symptoms were reported. She had no history of other vascular involvement or of any other organ involvement. She smoked occasionally for 2–3 years in her early twenties and reported minimal alcohol consumption. She had a contact allergy to latex. The patient was normotensive and body mass index was 28.5 kg/m2 in 2016.
Investigations
Blood tests were unremarkable: creatinine, estimated glomerular filtration rate (slightly impaired at 68 mL/min/1.73 m2), thyroid stimulating hormone, glycated haemoglobin, liver function tests, cholesterol and C-reactive protein. Full blood count was normal. Antinuclear antibody test was negative.
Upon review in 2013 with a dermatologist, a punch biopsy was performed. Findings showed an intact epidermis and a superficial dermis with "red cell extravasation with a proliferation of small blood vessels, some of which are plugged with fibrin thrombi". There was also a finding of chronic inflammatory cell infiltrate. There was no necrosis of the vessel walls. This was considered in keeping with a vascular occlusive disorder and was reported to be "consistent with livedoid vasculopathy".
Treatment
One of the authors met with her in a routine GP clinic when she presented with a flare-up and the patient was prescribed an antibiotic. She understood her diagnosis as capillaritis at the time, which was reflected in her electronic medical record diagnoses which had not been updated to reflect the diagnosis of livedoid vasculopathy from 2013. The patient expressed a desire to 'try anything'. Given that there are no highly effective treatments for capillaritis, a Whole Foods Plant-Based (WFPB) diet was discussed as untested for capillaritis but health-promoting for vasculature, including endothelial cells, which might plausibly help with presumed capillaritis. The patient was recommended to obtain Dr Esselstyn’s 'Prevent and Reverse Heart Disease'4 book from the library as this discusses the mechanisms by which endothelial function improves with a WFPB diet, and the patient was also referred to the accompanying cookbook.
A WFPB diet includes all vegetables, fruits, legumes, grains, herbs and spices. High-fat plant foods like avocado and coconut are limited. Meat, dairy, eggs, fried foods, heavily processed foods and all refined oils are excluded.5 The WFPB diet has been shown to improve cardiovascular health with few to no side effects.5 6
Outcome and follow-up
The patient presented 1 month after the first consultation to thank the GP. She reported improvement in lesion healing, with symptoms being less bothersome than they had been in 'years'. In March 2017, 1 year following the first visit, she had improved to the point where her symptoms had settled. This was the first time in approximately 8 years that the patient had been completely symptom-free, and she discontinued the compression stockings at this point.
Since 2017 the ulcerations have only recurred with periods of poor dietary adherence. Around 2017 the patient gauged her overall dietary adherence at about 90%. Minor dietary indiscretions might result in ulcerations, but these were less painful and irritating than before. In 2018 she felt that she had 'a new lease on life' and had been completely free of symptoms for 18 months. However, from Christmas 2019 (figures 1 and 2) and for several months after (to quote the patient):
“I lapsed badly. Fish and chips, pies, ham and cheese sandwiches, and in Feb/March my feet developed those awful sores” (see photos). “I was in a lot of pain again …” She identified fatty meats, cheese, oil as potential culprit foods.
Ulceration lateral malleolus, January 2020.
Ulceration medial malleolus, January 2020.
The patient subsequently had a 14-day course of amoxicillin+clavulanic acid along with resuming a WFPB diet. Since she has been '100%' sticking with her WFPB diet, her symptoms remain quiescent (figures 3 and 4).
Anterior view legs, June 2020.
Posterior view legs, June 2020.
Discussion
In livedoid vasculopathy there is "not a single best efficacious treatment".7 Although livedoid vasculopathy can remit spontaneously, the immediate and repeated recurrence of severe symptoms on reduced adherence to the WFPB diet makes a causal relationship plausible.
The symptoms of livedoid vasculopathy are related to vascular health. We propose several potential mechanisms although, given the complexity of diagnosis and treatment, more research is needed:
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Restoration of vascular endothelial cell function allows for increased endogenous production of nitric oxide, which has anticoagulant and anti-inflammatory effects.4 Certain foods, such as high-fat meals, can damage endothelial cells of the arteries and prevent them from producing nitric oxide, such that a single high-fat meal can transiently impair endothelial function.8 Because elevated triglycerides or cholesterol, and hypertension prevent L-arginine from being able to form nitric oxide, poor vascular health may predispose an individual to livedoid vasculopathy.4 People eating a vegetarian diet have significantly better vasodilation than those eating a standard Western diet, even when matched on characteristics such as serum glucose, lipid profiles and thyroid dysfunction.8 9
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Animal products, which are rich in saturated fat, can damage the intestinal endothelium when consumed, increasing gastrointestinal permeability (‘leaky gut’).10–12 This increased permeability can allow incompletely digested foreign proteins to enter the circulation.12 Following the molecular mimicry hypothesis, antibodies can form against the foreign antigen and cross-react with endogenous human epitopes.13 14 Animal protein epitopes are likely a more common immune trigger than plant protein, given there is more common DNA shared between humans and animals than humans and plants.13 14 When the antigen protein is removed from the diet, it would follow that symptoms would settle. An observed example of this is the cross-reaction of antibodies to cow’s milk proteins and human collagen in patients with rheumatoid arthritis.13 14
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A third mechanism is translocation of small bacterial endotoxins into the circulation. These have been shown to trigger acute inflammation.12 Bacterial toxins have been determined to originate from animal foods rather than commensal, as this is not observed with consumption of fruit and vegetables.10–12 Even one meal containing an animal product causes inflammation that peaks within 2–4 hours.8 10 With regular meals every 3–6 hours, this can provoke a state of chronic low-grade inflammation.12 This is less likely considering that inflammation is not thought to be the primary driver to the response seen in livedoid vasculopathy, and her C-reactive protein was normal when tested.
A WFPB diet can address the above possible mechanisms which, alone or in combination, may be contributing to or causing livedoid vasculopathy.
Learning points
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Livedoid vasculopathy is a condition with no previous published instances of dietary therapy.
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The mechanism for improvement in this case may be due to improved endothelial function.
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Further research is needed.
References
Footnotes
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Contributors NW identified and managed the case. MS and NW prepared the manuscript. BD and PM revised the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests MS and NW offer free online resources plant-based diets.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
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