Several systemic disorders have been associated with causing secondary oral burning. These may include neuropathy of undiagnosed, poorly controlled or even well-controlled diabetic patients. Burning discomfort caused by peripheral neuropathy (nerve damage) can affect any peripheral nerve including those that innervate the tongue. Neuropathy can also be initiated by chronic liver or kidney diseases, by HIV infection, by oral candidiasis, by vitamin B deficiency and some other systemic diseases. To date, however, only diabetic neuropathy has been reported as a possibly controllable cause of tongue burning sensations.7
Hypothyroidism has also been associated with burning in the oral cavity, especially the tongue. Although the cause of this association is unclear, the diagnosis and treatment of this endocrine disorder may reverse the burning discomfort. One oral side effect of hypothyroidism is tongue enlargement, and it is theoretically possible the enlargement increases tongue irritation from excessive contact with the teeth and possible tongue thrusting or bruxing.58 Gastroesophageal reflux disease (GERD) is sometimes associated with oral burning probably due to regurgitation of stomach acids into the oral cavity. This too is reversible with successful treatment.38,62
Burning mouth is more common in peri-menopausal or post-menopausal women suggesting a hormonal deficiency as an etiologic factor. However, ironically although hormonal supplementation may markedly relieve menopausal symptoms, it does not always alleviate all burning discomfort.53
Other associated systemic conditions may include, autoimmune connective tissue diseases, trigeminal neuralgia, multiple sclerosis and Parkinson’s disease.62,65 Several case reports have described oral burning sensations in drugs falling into the categories of antiretrovirals, antiseizure agents, antidepressants and several antihypertensives. The antiseizure drug clonazepam and the antidepressant drugs fluoxetine, sertraline and venlafaxine are of special interest since these two drug groups have paradoxically been used in treatment of BMS. Clonazepam is reported to be one of the most effective agents in controlling BMS. Among the antihypertensive drugs, angiotensin converting enzyme inhibitors appear most likely to induce burning mouth.54 Other reversible systemic conditions possibly associated with oral burning include nutritional deficiency (vitamin B12, folic acid, zinc) and iron deficiency anemia.60,62