MIX Disease: Diagnosis and Treatment
by V. Kim Kutsch, DMD., Carri Cady, RDH
Introduction
Medication-induced xerostomia (MIX disease, an acronym first introduced by Edwin Zinman) is becoming a more common problem for Americans. There are many potential causes of xerostomia, or dry mouth, and these causes include loss of saliva production as part of the natural aging process,1 Sjogren's Syndrome,2 radiation to the head and neck,3 and medication-induced xerostomia.4 There are now about 3000 prescription medications that list xerostomia as a possible side effect,5 but drug companies by-and-large have not included specific labeling to alert the consumer about xerostomia and its increased risk for dental caries.6 MIX disease affects people of all ages. The average person has no idea what xerostomia is, so the current drug labeling has little or no significance for them.
Causes of Xerostomia
Xerostomia or dry mouth is a condition where the patient has insufficient saliva flow to maintain oral health. Symptoms may range from irritation, inflammation, and/or recession of the soft tissues to rapid carious destruction of the hard tissues. Other signs and symptoms include candidiasis and burning mouth syndrome. This is a condition becoming more problematic as people are living longer and frequently taking multiple medications. It is not unusual in a healthy patient for saliva to naturally decrease during the aging process. Mouth breathing, particularly when sleeping because the saliva flow decreases, also will lead to dry mouth symptoms for some patients. Patients with sleep apnea and using a continuous positive airway pressure (CPAP) device may experience xerostomia. Other causes for xerostomia are post-radiation therapy that affects the major salivary glands and Sjogren's syndrome, which is an autoimmune disease that affects saliva flow. However, the most common cause of xerostomia today is medication-induced.
Drugs Causing MIX Disease
Many drugs list xerostomia as a potential side effect. The most common classes of xerostomic medications include antihistamines, antihypertensives, and methamphetamines, but many drugs commonly contribute to dry mouth and the multiple drug combinations that many patients are taking compounds the problem. This condition is prevalent in many senior patients but also is being seen in children taking antihistamines for asthma, antidepressants, and behavioral modification drugs for ADD7. It is also common for patients experiencing dry mouth conditions to suck on hard candy to stimulate saliva flow. The continuous exposure to sugar, resulting in continuous periods of acidic pH in the mouth, can have disastrous effects on the dentition of a person with inadequate saliva.
MIX Disease and Dental Caries Risk
A frequent and serious side effect of MIX disease is dental caries.8,9 The selection pressure in the biofilm for the acidogenic/aciduric bacteria responsible for caries is not sugar availability but rather protracted periods of low pH.10,11 In defense, the body has several protective mechanisms to maintain a near neutral pH and maintain the calcium phosphate mineral level in the teeth and to prevent the microbial shift from healthy bacteria to acidogenic/aciduric bacteria.12,13 The saliva, however, is the best adaptation for controlling pH as it contains a buffering system that helps maintain a healthy range of pH in the mouth.14 For patients with xerostomia or MIX disease, the lack of saliva reduces the body's ability to buffer the acidic conditions and selection pressure for the acidogenic/aciduric bacteria occurs, which results in dental caries.15,16 It is important to note that the cause of dental caries is not a lack of calcium and phosphate mineral or fluoride, but rather an inability for the dental biofilm to maintain neutral pH conditions.17
Diagnosis of MIX Disease
A good place to start in any caries risk assessment is with a simple validated caries risk assessment form. Ask the patient if they feel that they have a "dry mouth" or are taking medications known to cause xerostomia.18 (Many patients with xerostomia actually self-diagnose the condition.) Stimulated saliva flow can be measured by having the patient chew on soft wax and spit into a cup for 5 minutes. Average saliva flow should be about 1.0 mL of saliva created per minute. Less than 0.7 mL of saliva produced per minute is a sign of xerostomia. A review of the medications that the patient is taking will reveal the extent of MIX in the patient's condition.
Treatment Strategies
Recently, Takahashi and Nyvad19 demonstrated that even bacterial species previously considered commensal are capable of adapting to acidic conditions and becoming causative organisms in dental caries. These included Streptococcus gordonii, S. oralis, S. mitis, and S. anginosus, which they termed low-pH, non-mutans streptococci, in addition to Actinomyces species.19 Dental caries is now a disease not so much based on which specific bacteria are present, but rather what are those bacteria doing. Their recommendation for treatment strategies included good oral hygiene, effective dietary counseling, and then neutralizing strategies for the biofilm.19 The goal is not only to help neutralize the biofilm and select for healthy bacteria, but also not to cause the low-pH, non-mutans streptococci and Actinomyces species (commensal) to behave badly. For the patient with MIX disease, important treatment strategies might include a saliva stimulating drug, use of possible saliva substitutes, staying hydrated, and the importance of plaque control and healthy diets, and the daily use of oral care products that neutralize the mouth and keep the pH within healthy ranges. Effective neutralizing products are available from Carifree20 in gels, rinses, sprays, gums with combinations of fluoride, xylitol, and neutralizing and buffering agents.
Conclusion
For the patient taking medications that result in xerostomia, it is important to alleviate the immediate discomfort associated with dry mouth and also to educate them about the potential for dental caries and potential loss of their teeth. Practitioners must create individual treatment strategies based on the patient's needs and desires with the goal of creating a healthy pH balance in the mouth. It is incumbent upon the drug manufacturers to clearly label any potential for xerostomia, what that means in lay terms, and the possibility of severe dental caries with the potential for tooth loss.
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