Hapticophagia: Tactile chew cravings in iron deficiency anemia
Authors: Caleb J. Scheckel, Didar Yanardag Acik, Aishwarya Ravindran, Ariela Marshall, Ronald Go
Journal: American Journal of Hematology (2020)

Pica (allotriophagia), the compulsive craving and consumption of non-food substances, is a well-documented symptom associated with iron deficiency anemia (IDA). Commonly consumed substances include ice (pagophagia), cornstarch (amylophagia), and clay (geophagia). Olfactory cravings associated with IDA are a recently described phenomenon known as desiderosmia.1 We sought to understand an observed subset of patients in our practice with IDA reporting specific tactile cravings associated with mastication. Patients from the Mayo Clinic (Rochester, MN) and Adana Training and Research Hospital (Adana, Turkey) Hematology practices who self-reported tactile mastication cravings during initial evaluation for IDA between 1/1/18 and 6/30/19 were included. Information recorded included sociodemographics, substance craved, IDA-related laboratory values, and symptom resolution after treatment. We observed 15 patients with IDA who self-reported chew cravings during initial evaluation. All patients were female and the median age was 44 years (33-78). Median baseline Hgb, MCV, and ferritin were 9.4 g/dL (6.6-12.9), 75.6 fL (59.1-95.1), and 6 μg/L (2-21), respectively. Tactile cravings included chewing gum (3), mastic gum (2), crackers (2), ginseng (1), dry oats (1), pickles (1), chips (1), sawdust (1), hard candies (1), popcorn (1), and knitting rope (1) (see Table 1). Many patients reported the frequency and satisfaction of these cravings resulted in jaw pain, as well as the persistence of cravings, despite this discomfort. Only 20% (3/15) reported concurrent ice pica. Twelve patients proceeded with observed treatment of their IDA with clinical follow-up and laboratory confirmation of iron repletion. Oral and intravenous iron replacement were used in 25% (3/12) and 75% (9/12) patients, respectively. Post-treatment median laboratory values include: Hgb 12.9 g/dL (10.8-15.1), MCV 82.3 fL (76.1-101), and ferritin 98 μg/L (24-398). 91.7% (11/12) reported resolution of chew cravings after iron repletion. The one patient with persistent symptoms had a baseline ferritin of 10 μg/L, improved to 398 μg/L after replacement, and settled back at 42 μg/L 3 months later. The biology of food cravings is complex, with both physiologic and psychologic inputs.2 Food cravings derive from the hippocampus and nucleus accumbens, regions of the brain responsible for memory and pleasure, respectively. Imbalances of hormones and neuropeptides such as leptin, serotonin, and dopamine can contribute to food cravings via impact on taste and smell receptors. Food cravings may also be due to the interplay of emotions and the endorphins that are released into the body after eating for comfort, which mirrors an addiction.3 While the relationship between IDA and pica is well documented, the physiology behind it remains unclear. The most widely accepted micronutrient deficiency hypothesis holds that patients consume non-food items in an attempt to augment deficiencies of iron, zinc, or other micronutrients. However, this hypothesis cannot explain pagophagia, as ice typically contains few trace minerals or iron. Other theories hold that ice consumption may counter reductions in alertness and central processing speed via changes in cerebral blood flow (dive reflex or sympathetic nervous system activation) or that ice consumption4 reflects an effort to soothe the glossitis that can accompany some micronutrient deficiencies.5 The impact of IDA on brain physiology is another important consideration. Iron is a key enzymatic cofactor in dopamine synthesis and iron deficiency can effect dopaminergic transportation, metabolism, and yield higher concentrations of monoamine oxidase (MAO). Murine models have demonstrated that iron deficiency results in an absolute decrease in D2 receptors in the nucleus accumbens while producing higher levels of MAO in the hippocampus.6 Disturbances in cerebral concentrations of either dopamine and/or MAO have been linked with clinical depression. The consumption of food can be a pleasurable experience for many with the accompanying dopamine release reinforcing the behavior. It is plausible that some patients with IDA seek out mastication of various food substances to abrogate the neurocognitive effects of relative dopamine deficiency and MAO excess. The fact that some patients within our cohort continued to have tactile cravings for substances even after they became associated with noxious stimuli, reinforces that tactile cravings in IDA may have neurochemical underpinnings similar to chemical dependency. Our patient experience provides suggestive evidence that oral tactile craving symptoms, distinct from ice pica, exists in a subset of patients suffering from IDA. For this we propose the term hapticophagia, derived from the Greek word "haptic" for tactile and Latin word "phagia" for eat or consumption. Our hope in naming this relatively unexplored symptom associated with IDA will encourage additional clinicians to share their experience and guide future investigations.