Background/Purpose:  The occurrence of multiple autoimmune disorders in individual patients is commonly observed.  Rarely, this is explained by recently recognized genetically based autoimmune polyendocrine syndromes.  Pernicious anemia accompanies other autoimmune disorders both in patients with and without these discrete syndromes.  The purpose of this study was to detect possible underlying vitamin B-12 (B-12) deficiency or pernicious anemia in a rheumatology clinic based on a simple neurologic exam of the feet.

Methods:   Patients seen in a rheumatology clinic over a six month period were examined for evidence of peripheral neuropathy.  If typical findings of stocking sensory loss at the ankle level were found a B-12 level was obtained.  If B-12 levels were low anti parietal cell and intrinsic factor antibody titers were obtained.  Methylmalonic acid (MMA) levels were obtained in patients without either antiparietal cell or intrinsic factor antibodies.  Clinical features of antibody positive patients as well as those with B-12 deficiency and elevated MMA levels were reviewed.

Results:  38 patients with-low B-12 levels were positive for antiparietal cell or intrinsic factor antibodies. An additional 10 patients with low B-12 and elevated methylmelanic acid levels were indentified.  Diagnosis among antibody positive patients included:  rheumatoid arthritis 9-including one with vitiligo, one with Grave’s disease, 2 with Hashimoto’s; lupus 5; primary Sjogren’s 3-including one with stiff man syndrome;  primary Raynaud’s 4;  polyarticular CPPD 3; tophaceous gout 3; vasculitis 2;  ankylosing spondylitis 1; and pyoderma gangrenosum 1. Diagnosis among antibody negative patients included osteoporotic fracture 4, osteoarthritis 4, lupus 2, rheumatoid 2, ankylosing spondylitis 2, tophaceous gout 1, CPPD 1.   Among the lupus and Sjogren’s patients there were 2 positive for both SS-A and SS-B, 3 for SS-A, 1 for SS-B, 3 with anticardiolipin antibody, and 3 with false positive VDRL.  Paraproteinemia was present in 3 patients.  Among the 15 male patients, 7 were being treated for hypogonadism.  Four patients had 25-OH vitamin D levels below 10 ng/ml, 9 patients had thyroid disease, 7 had diabetes, and 13 had a positive family history for either diabetes or an autoimmune disease. The MCV level and hemoglobin level was normal in all but 1 patient who drank alcohol excessively.

Conclusion:  Pernicious anemia and B-12 deficiency was observed in a wide spectrum of autoimmune and arthritic diseases, especially SS-A and SS-B positive individuals.  Other components of autoimmune polyendocrine syndrome including diabetes, thyroid disease, male hypogonadism, and low vitamin D levels, suggesting the possibility of celiac disease, occurred frequently in this study group.  Recognition of pernicious anemia should alert the clinician to the possible presence of other components of autoimmune polyendocrine syndrome and vice versa.  Also, B-12 deficiency can cause elevated MCV, foot complaints, constitutional symptoms, neuropathy that could be mistaken as a complication of the underlying disease or its therapy, and is associated with osteoporotic fractures.  A simple 30 second neurologic exam can lead to the diagnosis of this potentially treatable deficiency.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pernicious-anemia-and-vitamin-b-12-deficiency-in-autoimmune-disease-neglecting-the-feet-will-lead-you-astray/