Background/Purpose: The most familiar presentation of pernicious anemia is an elderly Northern European woman with hematologic and neurologic manifestations.  More recently the influence of Helicobacter pylori (H. pylori), autoimmune polyendocrine syndromes (APS) and paraproteinemia on the development of pernicious anemia has been recognized.  The purpose of this study is to document the spectrum of pernicious anemia as manifest in a cohort of pernicious anemia patients diagnosed in a rheumatology clinic.

Methods: A retrospective chart review of the history and physical, laboratory and x-ray studies was conducted among patients diagnosed with pernicious anemia over a 10 year period.  Pernicious anemia was diagnosed on the basis of a low vitamin B12 level and either intrinsic factor or anti-parietal cell antibodies.

Results: A total of 150 patients, 106 females and 44 males ranging in age from 32-101 years (mean 71.8) were diagnosed with pernicious anemia.  Referral was based on acute fracture of the spine or pelvis-41,RA-30, arthritis-30, osteoporosis-16, pain-15, autoimmune disease-9, SLE-7, psoriasis-2.  There was a history of major osteoporotic fracture in 54, heartburn-73, past peptic ulcer disease-16, lower esophageal ring-3, thyroid disease-42, type 1 diabetes-13, and vitiligo-2.  12 patients were on proton pump inhibitors and 5 were on H-2 antagonists. The mean BMI was 27.3.  101 patients had a sensory deficit at the level of the ankle, including 38 with findings of a glove and stocking sensory loss.  Only 25 patients were anemic with 2 patients having a MCV >100 fL and 5 with a low serum iron.  Folic acid was < 8 ng/mL in 19 patients with a predominance of intrinsic factor over anti-parietal cell antibody present (p=0.039).  Vitamin D levels were < 12 ng/mL in 13.  H. pylori was diagnosed on the basis of a positive urea breath test in 21 patients at the time of initial evaluation (Group 1).  Paraproteinemia was identified with serum immunofixation in 19 (Group 2).  Autoimmune disease diagnosis (Group 3) included RA-32, SS-a or SS-b positive Sjogren's 9, SLE -3, psoriatic arthritis-4, CREST-2, spondyloarthropathy-2,inflammatory bowel disease-2, anti-PLA2R+ glomerulonephritis-1.  Patients with thyroid disease-42 constituted Group 4, with the remaining 51 in Group 5.  Mean age of the groups was 65.8, 77, 66, 71.3, and 71.7 respectively.  There was a statistically significant increase of autoimmune disease present in H. pylori + Group 1 compared to the remaining 129 patients without H. pylori (p=0.0295).  No other statistically significant differences were noted between Groups 1-5 or between intrinsic factor and anti-parietal cell antibody positive patients.

Conclusion: Pernicious anemia is most likely to be found among rheumatology patients with fracture, primary Sjogren’s ,thyroid disease, vitiligo and other features of APS as well as in patients with paraproteinemia.  Patients with autoimmune disease and those with H. pylori infection present with pernicious anemia at a younger age.  The statistically significant correlation among pernicious anemia patients between H. pylori infection and underlying autoimmune disease supports the hypothesis that H. pylori can act as a trigger of an autoimmune response in a genetically predisposed host.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/helicobacter-pylori-infection-autoimmune-disease-and-paraproteinemia-influence-the-presentation-of-a-cohort-of-150-pernicious-anemia-patients-diagnosed-in-a-rheumatology-clinic/