Calciphylaxis, molecular mimicry and egg white albumin; an experiment, n = 1

Calciphylaxis is a rare type of wound that is associated with hyperparathyroidism and is most commonly seen in patients who are receiving kidney dialysis due to end stage renal disease. The condition is also associated with an eight times increased risk of morbidity (death) compared to patients who don’t have calciphylaxis.

The term calciphylaxis came to my attention this year when I found out that I had an elevated parathyroid hormone level. See the following posts for more information about calciphylaxis and about other symptoms associated with elevated parathyroid hormone:

  1. Secondary hyperparathyroidism, calcium deficiency and irritability
  2. Elevated parathyroid hormone (PTH) and 1-25-D, calcium deficiency and calciphylaxis‘Calciphylaxis is more of a risk with end stage renal disease but it has also been found in people who had normal vitamin D levels and normal kidney health. And “high dose vitamin D administration is capable of inducing STC (soft tissue calcification) and calciphylaxis in murine models. [56, 57] In an attempt to reestablish normal calcium-phosphate homeostasis, ESRD patients receive vitamin D analogs that could theoretically increase their risk of calciphylaxis if hyperphosphatemia and hypercalcemia ensued. [58, 59]” [3]

    “Experimental sensitizing events and agents included nephrectomy and exposure to parathyroid hormone (PTH) and vitamin D. Substances used as challengers included egg albumin and metallic salts. Calciphylaxis was the end result.4  – from a 1962 study, abstract is free. [4.5]’

  3. Secondary hyperparathyroidism and calciphylaxis symptoms; an update with lab values
  4. Calciphylaxis may be caused by several different nutrient issues

Antibodies against chemicals that are a normal part of the human body can develop in autoimmune disease. The term molecular mimicry refers to the autoimmune antibodies that may be manufactured by overactive white blood cells in response to a large foreign protein allergens that may have made it through ‘leaky’ intestinal walls into the blood stream.  See: Robert S. Fujinami, et. al., Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease, Clin Microbiol Rev. 2006 Jan; 19(1): 80–94.

To skip to the point, egg white albumin is very similar to the albumin found in human blood. It is an essential protein within plasma and it helps maintain fluid balance between the blood plasma and extracellular fluid (too much extracellular fluid would be noticeable as edema – puffy ankles from excess fluid collecting outside of the cells and blood vessels.

After finding the research about egg white albumin on September 24, I eliminated egg white from my diet. My symptoms did get better fairly rapidly but I had tried a few strategies at the same time so it wasn’t clear whether stopping egg white had been necessary for the symptoms to improve or whether the other strategies I had tried may have been adequate on their own — so after feeling better for a couple weeks I decided to retry egg white to see if eliminating them had been an unnecessary strategy. Sadly I found that the day after trying egg white albumin again (in the form of baked chocolate chip cookies) my skin sores returned. I stopped eating egg white again. The sores aren’t as bad as they had been in September but calciphylaxis sores are termed necrotic wounds and necrosis means death and dead tissue in wounds can lead to gangrene and septic bloodsteam infections.

Open sores with oozing plasma that sticks to fabric is unpleasant and painful as well as being associated with an eight times increased risk of morbidity (which means death of the patient).

So I don’t have proof that my body set up autoimmune antibodies to albumin but I would rather stop eating egg white than continue having oozing sores – that is my choice, it is my body and I should have a right to take care of it to the best of my own ability rather than having to follow mainstream medical advice about a condition that is not well understood but is associated with an increased risk of death.

For more information about albumin antibodies and autoimmune disease see:

  • Rodríguez-Juan C, et. al., Increased levels of bovine serum albumin antibodies in patients with type 1 diabetes and celiac disease-related antibodies., J Pediatr Gastroenterol Nutr. 2003 Aug;37(2):132-5.
  • Excerpt from Abstract: “Although 46% of patients with autoimmune thyroiditis had positive results, the level detected (22.1 +/- 8.7 AU) was significantly lower than that recorded in patients with type 1 diabetes who had celiac disease antibodies (P = 0.04) and celiac patients (P = 0.04). Healthy volunteers showed no antibodies against bovine serum albumin.”  “Thirty-one percent of patients with diabetes yielded a positive result…” End stage renal disease is actually a significant risk for people with autoimmune Type 1 Diabetes because diabetes can cause an increased load on the kidneys from excess blood sugar and increased leaking of protein into the urine. Thirty-one percent of them might benefit from avoiding beef (bovine) or egg white albumin – but more research would probably be necessary before an ‘evidence-based’ recommendation could be made – except Rodriquez- Juan C, et al, did get a nice start on the project.

 

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

Calciphylaxis may be caused by several different nutrient issues

Calciphylaxis usually includes an imbalance of calcium and phosphate and a deficiency of protein C may also be involved. Protein C deficiency may be caused by genetic or acquired reasons. Protein C is involved in blood clotting. Vascular and soft tissue calcification frequently is also present in patients with calciphylaxis symptoms. The mineral content of the calciphylaxis sores has been found to resemble the mineral balance of bone.

Imbalance in vitamin D and hormone D metabolism might affect magnesium levels in some unusual cases and may promote intestinal malabsorption of magnesium. However elevated magnesium is more typically found in patients who have calciphylaxis as a side effect of dialysis in end stage renal disease. The kidney disease causes an abnormal lack of hormone D because the kidneys in normal health are the only place where vitamin D is activated into the hormone D form.

These are copies of links that I was reading and Tweeted last night:

  1. Mineral substance of bone tissue and of experimental cutaneous calcinosis in rats: chemical analysis and ESR study.
  2. Calciphylaxis assoc w cholangiocarcinoma… /heparin & vit K didn’t help/ Thrombosis & protein C deficiency involved/
  3. Retrospective analysis of tissue plasminogen activator as an adjuvant treatment for calciphylaxis. /Ca P homeostasis/
  4. Calciphylaxis… “the reported median survival time is 2.6 months after diagnosis,”
  5. Aggressive calciphylaxis in end-stage renal disease… /assoc w vascular & soft tissue calcification/
  6. Calciphylaxis is a cutaneous process without involvement of internal organs… /assoc w vascular calcification/
  7. Net-like pattern of calcification on plain soft-tissue radiographs in patients with calciphylaxis. – PubMed – NCBI
  8. Is calciphylaxis best treated surgically or medically? – PubMed – NCBI
  9. Calciphylaxis in a morbidly obese woman w RA presenting w severe weight loss & vit D def. /pamidronate & D tx worked/
  10. Calciphylaxis in the absence of end-stage renal disease. – PubMed – NCBI /low vit D but tx surgery/
  11. The surgical management of renal hyperparathyroidism. – PubMed – NCBI
  12. Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment. – PubMed – NCBI
  13. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. /low 25D w 2ndary hyperPTH in sunny climate

  14. Bone metabolism in celiac disease. – /following gluten free diet for 6 mo normalized 25D, calcium & PTH levels/

  15. Hypomagnesemia. Suppression of secondary hyperparathyroidism in chronic renal failure. – PubMed – NCBI

  16. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. – PubMed – NCBI
  17. Recent data on magnesium & osteoporosis. “Mg def in post-menopausal osteoporosis, prob caused by Mg malabsorption.”
  18. [The significance of magnesium in medicine. (II) Disturbances of Mg metabolism & their treatment (author’s transl)].
  19. Metabolic disorders of cattle. /pellagra discussed, zinc, B6 Cu Mg def, malabsorption, iron overload can deplete B3/

Why do I care? because even though my symptoms are unusual I feel that I still deserve individualized health care. As a dietitian I was taught to look up information about any unusual diagnoses that patients might have and to provide individualized guidance if available or provide background information to help patients be able to make more informed choices about their treatment plan.

I also care because I think women deserve individualized healthcare even if we may get emotional or moody. Physical and mental illness symptoms can be related to underlying issues and simply medicating a symptom not only fails to address the underlying issue but it also fails to look for an underlying issue which can be life threatening if care is delayed in acute situations:

Whether male or female in a for-profit health industry being your own patient advocate or hiring a professional patient advocate may be life saving when navigating the increasingly complex health care system.

See the previous post for my own patient struggles with symptoms of hyperparathyroidism and calciphylaxis like sores: Secondary hyperparathyroidism and calciphylaxis symptoms; an update with lab values

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

Secondary hyperparathyroidism and calciphylaxis symptoms; an update with lab values

Last month I described some health difficulties that I had been experiencing for quite awhile. Lab tests that had been drawn earlier in the summer suggested that the problem might be secondary hyperparathyroidism and I also had been having a number of odd symptoms including calciphylaxis that can be associated with secondary hyperparathyroidism but is a more common in end stage renal disease (ESRD) particularly for patients on dialysis who were also receiving calcium supplements (and calciphylaxis is associated with eight times increased morbidity in ESRD). In the second post I reported that I was already feeling much better on the treatment plan that I had developed for myself.

I started taking 300-500 mg calcium per day based on the theory that the symptoms were related to calcium deficiency secondary hyperparathyroidism. I also increased my protein intake except for eliminating egg white and tree nuts from my diet – as a precaution in case I had developed autoimmune sensitivity to those protein sources which I had been eating more regularly than other foods during a time when I wasn’t eating enough overall. A steroid skin cream containing Triamcinolon 0.5% applied twice a day helped the calciphylaxis like skin sores heal. And I started taking 40 mg Benicar/olmesartan per day in an attempt to modify the low vitamin 25 D and vitamin 1, 25 D > 42 pg/mL. Levels of vitamin 1, 25 D above 42 pg/mL signals the bones to release calcium and phosphorus and can increase risks of osteoporosis and soft tissue calcification. [1, 2: MPKB- Science behind olmesartan (Benicar).]

  1. Secondary hyperparathyroidism, calcium deficiency and irritability, 
  2. Elevated parathyroid hormone (PTH) and 1-25-D, calcium deficiency and calciphylaxis, 

The 6/15/15 lab values:

  • Parathyroid hormone level – PTH Intact – 154.1 pg/mL — normal range: [15.0-75.0]
  • Calcium – 8.8 mg/dL — normal range: [8.4-10.2]
  • Phosphorus was not ordered but would probably be good to check.
  • Vitamin D, 25 – 10.9 ng/mL — normal is considered: [30.0-100.0]
  • Vitamin D 1, 25 – 55 pg/mL — normal is considered: [18-72] (the active hormone D)

The 10/12/2015 lab values:

  • Parathyroid hormone level — PTH Intact — 66.1 pg/mL — normal range: [15.0-75.0]
  • Calcium — 9.3 mg/dL — normal range: [8.4-10.2]
  • Serum Phosporus — 3.6 mg/dL — normal range: [2.5-4.5]
  • Vitamin D, 25 — 18.4 ng/mL — normal range: [30.0-100.0]
  • Vitamin D 1, 25 — 36  pg/mL — normal range: [18-72] (the active hormone D)

So I started taking calcium supplements and 40 mg of Benicar on September 23 and on October 12 my parathyroid hormone level is back within the normal range. My active 1, 25 D is below the osteoporosis inducing level of 42 pg/mL and my inactive vitamin 25 D level increased from 10.9 to 18.4 ng/mL — even though I am not taking vitamin D supplements but I do get more than fifteen minutes of sunshine most days of the week. My calcium level is still within the normal range but it went up from near the low end of the range to closer to the middle, from 8.8 to 9.3 mg/dL.

During the last couple days the calcium supplements have been causing me to have increased muscle cramps and irritable mood and I found that soaking in Epsom salt tub or footbath helped reduce the muscle cramps and bad mood. So the balance between magnesium and calcium intake is important and intestinal malabsorption of magnesium may be part of the underlying problem.

Overall I’m feeling much better than I was in early September before I started taking the calcium supplements. I had been having a racing heartbeat on very little exertion (like tachycardia) and for a long time I had been having an internal jittery-ness that felt like a bottled up pressure that needed a release valve or pinprick to pop the overfull bubble. The painful skin sores had been a fairly new and very unpleasant development. So yippee I have skin again! And I can walk downstairs without having to pause to let my heart rate slowdown.

I still have autoimmune thyroid antibodies but my thyroid hormone and thyroid stimulating hormone levels are within normal range — 10/12/2015 lab values:

  • Serum Thyroglobulin AB — 41 IU/mL — normal range: [0-40]
  • Serum Thyroid Peroxidase AB — 301 IU/mL — normal range: [0-34]
  • T3 Free Serum — 4.09 pg/mL — normal range: [2.77-5.27]
  • T4 Free Serum — 1.14 ng/dL — normal range: [0.65-1.86]
  • Serum Thyroid Stimulating Hormone — 1.20 mIU/L — normal range: [0.46-4.68]

To prevent autoimmune hyperthyroid symptoms I have been avoiding foods containing gluten and iodine sources since receiving the diagnosis in 2013. The gluten protein molecule contains a section called gliadin that is chemically similar to the thyroid hormone. The chemical similarity between gliadin and the thyroid hormone may allow autoimmune thyroid antibodies to develop in susceptible individuals, so avoiding gluten in the diet may be helping reduce or prevent the production of the autoimmune thyroid antibodies.

–The bad news – my endocrinologist still wants me to take a vitamin D supplement for my low vitamin D. [previous post: Whether to be compliant or to be healthy seems like an easy question to answer

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./