Dental treatment of a Seven-Year-Old Child with Mastocytosis

1. Introduction

Mast cells, also known as mastocytes, are immune cells triggered during allergy attacks. Mastocytosis is a heterogeneous group of clinical disorders that is characterized by a pathologic proliferation and accumulation of mast cells in a variety of tissues, most often the skin [1]. The disease presents in two primary age-related patterns as follows: pediatric-onset mastocytosis and adult-onset mastocytosis, which may differ in their clinical manifestations and disease course. Pediatric-onset mastocytosis is commonly diagnosed prior to two years of age and usually consists of cutaneous disease, with urticaria pigmentosa (UP) the most common pattern, representing 70-90% of the cases [2]. The term “urticaria pigmentosa” was introduced by Sangster in 1878 [3] because of the gross appearance of the lesions.

There is an equal gender distribution, and it seems that no race is predominant. Mastocytosis is considered to be an orphan disease and its cause is still unknown. There are no epidemiologic studies to define the precise incidence, point prevalence, or cumulative prevalence of mastocytosis in the general population. At the consensus meeting of mastocytosis experts in Boston 2010, a general cumulative prevalence of approximately one in 10,000 persons was estimated [4]. Because of the differences in diagnostic criteria and experience between departments, in many countries there is an attempt to create centers of excellence for the disease.

In regards to the onset age of mastocytosis, 60-80% of the patients have their onset during infancy and in some cases lesions, as well as mastocytomas, can be present at birth [2]. The lesions in UP can be red, brown or yellow, oval or round, multiple in the form of nodules or single and their diameter can expand from a few millimeters to one or two centimeters. They usually affect the trunk and extremities, but they may be present in any skin or mucosal area. Patients have mast cell mediator-related symptoms such as erythema, swelling and blister formation spontaneously or after exposure to different stimuli. The Darier sign is associated with the disease due to the release of histamine, prostaglandins and leukotrienes from dermal mast cells, but is not present in all patients. In children, lesions tend to resolve by the age of ten years and if they appear after this age, they tend to persist [5]. It has been stated that total to partial resolution of pediatric-onset mastocytosis would happen in more than 50% of patients [6]. Diffuse cutaneous mastocytosis is more aggressive and the symptoms-usually systemic- can be more severe and persistent. Therapy is primarily symptomatic since no medication is curative.

Acute episodes of cyanosis and respiratory arrest are uncommon but can arise with acute mast cell activation events. Physical stimuli such as exercise, spicy food, exposure to high/low temperature, sunlight; chemical stimuli such as aspirin, radiographic dyes, non-steroidal anti-inflammatory agents and narcotics and also emotional factors such as anxiety and stress can be triggering factors, resulting even in life-threatening anaphylactic reactions [7].

Acute episodes of cyanosis and respiratory arrest are uncommon but can arise with acute mast cell activation events. Physical stimuli such as exercise, spicy food, exposure to high/low temperature, sunlight; chemical stimuli such as aspirin, radiographic dyes, non-steroidal anti-inflammatory agents and narcotics and also emotional factors such as anxiety and stress can be triggering factors, resulting even in life-threatening anaphylactic reactions [7].

It is clear that in the dental environment fear and anxiety are usually present, especially in children. Invasive intervention in patients with mastocytosis should be avoided and when needed the dentist should always be aware of the medical history, take specific precautions to prevent mast cell activation and be ready to use resuscitative drugs in case of anaphylactic reaction. Fluids, epinephrine, antihistamines, and pressor agents are often required. Patients with mastocytosis are advised to wear medical alert bracelets and carry epinephrine-filled syringes with them.

2. Case Report

A seven-year-old girl was referred to a private pediatric dental practice in Thessaloniki. The girl was accompanied by her parents. Their main concern was that the girl may have an allergy to local anesthetics as well as antibiotics and according to her dentist’s diagnosis she needed dental treatment. Thus, prior to proceeding to any dental procedure, it was reassured that the parents had brought an adrenaline shot with them. Furthermore, injectable epinephrine was also available in the dental office for the management of a potential anaphylactic shock [8]. There was not history of pain or swelling. The clinical and radiographic examination revealed poor oral hygiene and a total of 12 primary teeth (#51,52,54,55,61,62,64,65,74,75,84 ,85 )affected by dental caries. Two bitewing radiographs were taken, revealing the proximity of caries to the pulp on the left mandibular first primary molar (Fig. 1). She had a complete primary dentition and the first permanent upper and lower molars. The upper front teeth had mobility, but the girl had obviously delayed tooth eruption [9]. The mother reported that she brushes her daughter’s teeth once a day with fluoridated toothpaste, but the child’s diet included many intakes of sugar daily. The patient’s level of cooperation was good enough, Frankl Scale: 3 (positive) [10]. The child didn’t have any oral habits. A prophylaxis and fluoride treatment were accomplished in a second visit.

Fig. 1. Intraoral radiographs.

2.1 Medical History

The girl had a normal delivery at birth. Generalized skin lesions were observed by the family and the diagnosis of urticaria pigmentosa was made at the age of six months old by an allergist, based also on positive Darier´s sign. The patient’s daily medication included 5ml of an antihistamine syrup (rupatadine) and application of a hydrocortisone cream. There were multiple, sized from one to five millimeters maculopapular lesions concentrated mainly over her trunk and her neck (Fig. 2). The lesions were yellowish-pale red in color. There was a positive history of allergies to aspirin, amoxicillin, foods, and high temperature. The patient’s weight was 26kg. She was hospitalized in the past for flu complications, but she had never been treated with general anesthesia. The child was followed closely by a pediatrician and an allergist. At school and outdoor activities, she was supervised by a nurse, who always had an adrenaline shot with her in case of emergency.

Fig. 2. Extended maculopapular lesions -characteristic of mastocytosis- over the girl’s trunk and neck.

The distribution of the number of data according to each of the 48 classes in the model was presented in Fig. 2. General distribution of the data set was not regular. Although the irregularity of the distribution was a compelling factor for training the model, this situation was not considered as a disadvantage, since this irregular distribution may show similarity to the numbering distribution of the pediatric patients that the model encounters in real life.

3. DISCUSSION

Mastocytosis is usually diagnosed by hematologists or dermatologists. Children with mastocytosis should be monitored regularly by an allergist and their parents should be trained in how to manage attacks. Given their high propensity anaphylaxis, patients with mastocytosis should be tested for allergies prior to any dental treatment [12]. However, data may be difficult to interpret, and tests may be invaluable. A retrospective review of 64 patients with mastocytosis (31 children and 33 adults) correlated a severity scoring system with tryptase levels [13]. Serum tryptase levels are a reflection of mast cell burden and can serve as a reference point really valuable in the diagnosis of the disease and of possible anesthesia-associated adverse events [14]. Levels of tryptase higher than the normal range (11–15 ng/ mL) may indicate an increased mast cell burden and/or extensive level of degranulation [2].

Patients with urticaria pigmentosa may be susceptible to cardiovascular collapse due to excessive histamine release from mast cells, even during their stay at the dental office. Dental anxiety and emotional stress are probably the most concerning triggers, as they may cause severe reactions [15]. Symptoms are quite variable, ranging from mild pruritus to abdominal pain, or even anaphylaxis.

Several allergens have been identified on the dental office. Latex, zinc oxide, eugenol, nickel, chromium and even titanium have been related to allergic reactions on patients [16, 17]. In order to avoid a delayed allergic reaction to nickel or chromium, we preferred restoration with resin modified glass-ionomer cement on #74 instead of a stainless-steel crown as indicated. Also, drugs commonly used and prescribed like local anesthetics, non-steroidal anti-inflammatory drugs and antibiotics have been reported as triggers for mast cell activation [12, 17]. Thus, the main goal in treating a child with mastocytosis is avoiding triggers that cause acute mediator release.

Although there are in the published literature cases where patients are treated under GA without any complication [15, 18, 19], previous reports had presented a number of side effects including anaphylaxis, cardiovascular collapse, bleeding and even death [20, 21]. Because mast cells are implicated in the pathophysiology of anaphylaxis and patients with mastocytosis have an increased mast cell burden, drugs used in anesthesia degranulate mast cells and raise justified concerns about potential adverse reactions [14].The incidence of anaphylaxis is much higher on patients with mastocytosis [22]. Thus, treating them in a non-hospital environment can be perilous. In this case, GA was not preferred as too risky. Instead, we decided to provide dental treatment in the operating theatre of a private hospital clinic in order to allow both meticulous monitoring and systematic desensitization of the dental procedures. Of course, to take such a decision, consultation with the medical team and written consent of the parents are necessary.

Patients submitted to high-risk procedures should be premedicated with H1 and H2 blockers at maximum dose and if necessary, diazepam derivatives, as they can be useful in order to prevent stress-induced mast cell mediator release [12, 23]. It is also recommended to have adrenaline ready to use in case of emergency. H1 antihistamines, such as hydroxyzine, inhibit the effects of histamine on capillary permeability and they also possess local anesthetic activity. The side effect with the highest incidence of all H1 blockers is sedation [15]. H2 antihistamines, for instance ranitidine, are indicated for amelioration of gastrointestinal symptoms including bleeding and peptic ulcer. Those symptoms are derived from the increased secretion of gastric acid secondary to increased histamine levels.

In local anesthesia we used the minimum required dose of articaine per quadrant. If local anesthesia is needed amide-type anesthetic agents are recommended and not ester-linked. There is no reason to avoid local anesthetic nerve block, while the vasoconstrictor (like adrenaline or epinephrine), is useful in case histamine release occurs. Medically indicated drugs should not be eliminated from therapeutic consideration unless there is a clear prior history of sensitivity2.

Patients suffering from mast cell disease may be more prone to particular oral pathologies, such as periodontal disease, jaw osteoporosis. Medications can make them more susceptible to dental caries and mucosal lesions [12]. Antihistamines have been shown to greatly affect salivary glands in result of the diminishing of histaminic effects on salivary secretion [24]. Xerostomia may increase susceptibility to dental caries, candidiasis and other infections, and mucosal inflammation [25]. These patients should be submitted to regular dental examinations. Our patient’s parents were given meticulous oral hygiene instructions, including the need to use a fluoridated dentifrice and to brush twice daily in order to prevent caries and gingivitis.

4. CONCLUSION

In children with mastocytosis, mast cells are triggered much more easily and that causes allergy-like symptoms. The dentist should be aware of the medical history especially the duration and the factors provoking mediator release. The fear of reactions to drugs and materials used in procedures for the benefit of the patient must be evaluated, placed in perspective, and not be allowed to interfere with optimal patient care. Team approach is recommended in treating patients with mastocytosis, ideally in a hospital setting, with or without general anesthesia. H1 and H2 blockers can restrict mast cell degranulation, however dental staff and family should always be prepared to face an anaphylaxis reaction.