Her immune system was already implicated in diseases affecting her liver, bile ducts, and large intestine. Then a clue in her blood revealed another target: her stomach.
The 40-year-old woman in China had severe iron deficiency. But doctors could find no sign that she was losing blood. Instead, her body was struggling to absorb iron from food.
The cause was a fourth autoimmune disease.
Autoimmune diseases develop when the immune system, which normally fights infections, mistakes the body's own healthy cells for a threat and attacks them.
The unusual case, published in Frontiers in Immunology, also presented doctors with a diagnostic puzzle: Did the woman have a rare syndrome that connects several autoimmune diseases?
One of the woman's diagnosed conditions was ulcerative colitis, which inflames the lining of the large intestine and can cause pain, diarrhea, and bleeding. Her ulcerative colitis was in remission when doctors investigated her iron deficiency, making intestinal bleeding less likely.
She also had autoimmune hepatitis, in which the immune system mistakenly attacks and inflames the liver. Unlike viral hepatitis, it is not caused by an infection.
Her third condition was primary sclerosing cholangitis. It scars and narrows the tubes that carry bile from the liver. Bile is a fluid that helps the body digest fats.
Blood tests revealed that her hemoglobin had fallen to 89 grams per liter. Hemoglobin is the protein in red blood cells that carries oxygen around the body.
Doctors searched for a source of bleeding. Repeated tests found no hidden blood in her stool, and a gynecological examination found no apparent gynecological source of blood loss.
That left another possibility: perhaps her digestive system could no longer absorb enough iron.
When doctors examined her stomach, they found that part of its inner lining had become severely thinned. Under a microscope, immune cells could be seen inflaming the tissue. Many of the cells that normally produce stomach acid were damaged or missing.
The woman also had antibodies directed against her stomach's acid-producing parietal cells.
Together, these findings confirmed the fourth autoimmune disease in this patient – autoimmune gastritis.
Stomach acid does more than help digest food.
It also helps prepare dietary iron for absorption in the small intestine. When autoimmune gastritis destroys acid-producing parietal cells, reduced stomach acid can make iron harder to absorb, even if a person's iron intake is adequate.
The condition can also eventually interfere with vitamin B12 absorption, which the body needs to make healthy blood and nerve cells. But the woman's B12 level was still normal, consistent with evidence that iron deficiency can be an earlier warning sign.
The collection of illnesses resembled a rare condition called autoimmune polyglandular syndrome type 3B, or APS-3B, in which an autoimmune thyroid disease occurs together with autoimmune diseases of the digestive system.
The woman did have hypothyroidism, meaning she did not have enough thyroid hormone.
But her thyroid had been surgically removed because of thyroid cancer. Hypothyroidism is an expected result when the gland that produces those hormones is removed.
Doctors did not have the test or tissue evidence needed to show that her thyroid had also been attacked by her immune system. The case therefore resembled APS-3B but did not prove that she had the syndrome.
This means the woman had four confirmed autoimmune diseases. The clinicians attributed her iron-deficiency anemia to impaired iron absorption associated with autoimmune gastritis.
"This case indicates that when a patient has multiple autoimmune diseases, especially those involving the gastrointestinal tract, the possibility of autoimmune polyglandular syndrome should be considered," they explain in their case report.
Cases involving several autoimmune diseases are unusual but not unprecedented. ScienceAlert previously reported on a woman with three autoimmune conditions that went into remission after an experimental immune "reset".
Related: Study of a Million Blood Cells Helps Explain Why Women Face More Autoimmune Disease
The new report describes only one patient. It cannot tell us how common this combination is, whether one disease led to another, or whether everyone with several autoimmune diseases should undergo stomach tests. Some of the woman's earlier medical information was also unavailable.
Doctors prescribed iron supplements and planned to monitor her vitamin B12 and folate levels. They also planned another stomach examination with biopsies in 1–2 years because autoimmune gastritis can increase the long-term risk of certain stomach tumors.
The case shows that unexplained iron deficiency is not always caused by diet or blood loss. For someone already living with autoimmune disease, it may signal that the immune system is attacking another part of the body.
The research was published in Frontiers in Immunology.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.