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Mastocytosis – oral and dental manifestations and medical considerations for dental treatment: a case report Esti Davidovich DMD, MSc1, Lev Ronin MD2 and Diana Ram Dr. Odont3 1

Clinical Instructor, 3Senior Clinical Lecturer, Department of Paediatric Dentistry, The Hebrew UniversityHadassah School of Dental Medicine, Jerusalem, Israel. 2Department of Anaesthesiology and Critical Care Medicine, Hadassah Medical Centre Jerusalem, Israel Abstract The present case emphasises the importance of a multidisciplinary approach in treating a 6-year-old boy suffering from systemic mastocytosis. Mastocytosis is characterised by mast cell proliferation and accumulation within various organs, the most commonly affected of which is skin. The patient was scheduled for treatment under general anaesthesia. The medical, dental and anaesthetic considerations and treatment are presented. Key words: Mastocytosis, oral findings, dental treatment, anaesthesia, perioperative medicine

Introduction Mastocytosis is a clonal disorder of the mast cell due to proliferation and accumulation of these cells and their precursors within different tissues (bone marrow, skin, GI tract and spleen). The skin is the most frequently affected organ. The most common cutaneous form of mastocytosis is urticaria pigmentosa (UP), and is characterised by red-brown macules, papules, or plaques ranging in number from a few to thousands. Lesions may vesiculate in infancy (Hogan, 2005; Metcalfe, 2005; Valent et al., 2005). The increase in mast cell numbers in most patients is probably due to activating mutations in the c-kit receptor (Worobec et al., 1998). Another important pathogenetic cause is the abnormal expression of cell surface adhesion antigens on neoplastic mast cells (Metcalfe, 2005). Mast cells contain a range of active mediators in their granules, which are preformed and stored. They produce generated membrane-derived lipid mediators and are a source of multifunctional cytokines. The pathophysiology of mast cell disease can be divided into systemic and local effects. The systemic effects are related to the response of the tissue to the release of the above-mentioned mediators from the mast cells, or to local mast cell burden, or associated non-mast cell haematological disorders (Braverman, 1998; Koyamangalath, 2005). Mediator-related symptoms can include pruritus, flushing, syncope, gastric distress,

nausea and vomiting, diarrhoea, bone pain and neuropsychiatric disturbances. Systemic manifestations may cause severe end-organ dysfunction, for example, hepatosplenomegaly and bone marrow dysfunction (Escribano, 2006). Local manifestations of this disease arise from the effects of local collections of mast cells (Braverman,1998; Koyamangalath, 2005). The onset of mastocytosis occurs before the age of 2 years in 55% of the patients and from 2 to 15 years old in 10% of the patients. Most of the reported cases are in Caucasians, with males and females being equally affected. The prognosis depends on the age of onset; and is usually more transient and self-limited in children than adults (Hogan, 2005; Koyamangalath, 2005). Systemic persistent disease, higher risk of malignant transformation and poorer prognosis are found when the onset is after the age of 10-yearsold (Hogan, 2005; Metcalfe, 2005; Valent et al., 2005). Therapy is primarily symptomatic since no therapy is curative. Symptoms are variably controlled by adequate medications. Management of patients within all categories of mastocytosis includes: • Careful counselling of patients (or the parents in case of paediatric patients) and care providers • Avoidance of factors triggering acute mediator release (Table 1 summarises the substances that induce mast cell mediator release)

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Table 1. Factors that may induce mediator release from mast cells and should be avoided Pharmacological agents salicylates (Aspirin) NSAIDs codeine morphine thiamine quinine opiates gallamine decamethonium procaine radiographic dyes dextran polymyxin B scopolamine D-tubocurarine Food and beverages crawfish lobster alcohol spicy foods hot beverages cheese Activity physical stimuli emotional stress temperature extremes physical exertion Miscellaneous bacterial toxins, insect stings Table 2. Indication for the use of different kind of medications in mastocytosis Drug

Indication

H1 and H2 antihistamines Corticosteroids Epinephrine

To decrease pruritus, wealing, flushing, GI symptoms Injections to cutaneous lesions, for the control of malabsorption Acute anaphylaxis

• Treatment of acute and chronic mast cell-mediator symptoms

• If necessary, treatment of organ infiltration by mast cells (Escribano, 2006). The different medications and indications for use are presented in Table 2. (Hogan, 2005; Metcalfe, 2005; Valent et al., 2005). Complications include possible transformation to a haematologic malignancy, death secondary to mast cell degranulation and Mast Cell Leukaemia (Braverman, 1998; Koyamangalath, 2005; Metcalfe, 2005). There is a paucity of reports in the dental literature regarding mastocytosis. A case of systemic mastocytosis of a 4.5-year-old paediatric dental patient with mastocytosis has been reported (Nelson and Savelli-Castillo, 2002). In this reported case, the planned dental treatment was provided in an ambulatory setting utilising only nitrous oxide-oxygen

analgesia to provide sedation, with no local anaesthesia, and H1 and H2 antihistamines were used to prevent mast cell degranulation. The dental treatment provided included fissure sealants and shallow, resin-composite fillings. During general anaesthesia, trauma, stress, extreme temperatures and drugs may precipitate intra-operative mast cell degranulation. The aim of our case report is to describe the dental treatment under general anaesthesia of a child with systemic mastocytosis, and the medical considerations associated with the dental treatment.

Case report A 6-year-old boy was referred to the Department of Paediatric Dentistry at the Hebrew University, Hadassah School of Dental Medicine in Jerusalem by his paediatri-

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cian for dental treatment due to a dento-alveolar abscess and tooth pain. The boy was diagnosed as suffering from systemic mastocytosis, and no clinical signs of the disease were apparent. Consultation with his paediatrician revealed that he only suffered from cutaneous manifestations and no other organs were involved. He was mainly treated with antihistamines as necessary. On his first visit, the boy was not cooperative. Clinical examination revealed extensive caries and poor oral health. A dento-alveolar abscess related to the second maxillary primary left molar was clinically diagnosed and Amoxicillin 750mg/day was prescribed. Due to the extensive dental treatment plan, the lack of cooperation of the child, and the possibility of flare up of the disease with a concern of oedema, the boy was scheduled for dental treatment under general anaesthesia (GA). The treatment plan included a strict prevention protocol: prophylaxis, restorative treatment, extractions, fluoride application and meticulous oral hygiene instructions.

Figure 1. Carious lesions in the mandibular incisors as well as in the maxillary incisors and canines. Right maxillary incisor is missing.

Anaesthetic management The child was pre-medicated with Midazolam syrup 0.4mg/ kg. The induction of anaesthesia was performed by inhalation of sevoflurane and nitrous-oxide followed by the insertion of an I.V. catheter; 2mg/kg of Propofol I.V. was administrated followed by nasal intubation with careful fixation. Anaesthesia was maintained by propofol infusion at 10– 15mg/kg/h. Mechanical ventilation of lungs was instituted using a 2:1 nitrous-oxide/oxygen mixture. Standard monitoring (E.C.G., pulse oximeter, NJBP, Et CO2 analyser) was used. During the anaesthesia the patient was haemodynamically stable and the recovery was uneventful.

Dental management Local anaesthesia (lidocaine 2% with epinephrine 1:100,000) was added to perform the dental extractions. The child had deep carious lesions in all his primary teeth. The right maxillary incisor was missing. (Figures 1–3a and b). A rubber dam covered with Vaseline was used in order to prevent direct contact with the skin. The carious and mobile upper primary lateral and central left incisors were extracted. The maxillary primary second molars were extracted due to severe pulp inflammation and poor prognosis. Since extensive bleeding due to heparin release from the mast cells could be expected, local haemostatic agents (Gel-foam, topical thrombin, microfibrillar collagen and sutures) were prepared in advance. No excessive bleeding was observed and no haemostatic agents were used. Pulp haemostasis was achieved in the mandibular primary second molar, and a pulpotomy and placement of a stainless steel crown were successfully performed on this tooth. The other decayed teeth were restored with resinbond-composite restorations.

Figure 2. Deep carious lesions involving the maxillary primary teeth

After two hours supervision in the recovery room the child was admitted to the Paediatric Department of the Hadassah Children’s Hospital, and remained under observation for 24 hours. Four days later, when he was seen at a recall examination, the oral mucosa appeared intact. Neither pain nor sensitivity was reported.

Discussion This case report presents the dental management of a 6year-old boy with systemic mastocytosis who urgently needed dental treatment due to extensive dental caries and pain. The complexity of the disease and the clinical manifestations in this patient required a multidisciplinary approach before dental treatment could be performed. The main goal in treating a child with mastocytosis is to avoid triggers that can cause mast cell degranulation. Dental treatment in general and dental treatment under general anaesthesia (GA) in particular are stressful events that may cause acute mediator release. However in this case, GA was preferred in order to minimise the number of stressful episodes, as well as to allow meticulous monitoring and the possibility of appropriate reaction to an anaphylaxis shock. In addition, due to the lack of cooperation of the child, this

Davidovich et al.: Mastocytosis, oral findings, dental treatment

Figure 3a. Deep carious lesions involving the right mandibular teeth.

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Figure 4. lack of pulp haemostasis after pulp exposure due to deep caries.

and pressuring additives such as methylparben) should be avoided. Amide-type of local anaesthetics with adrenaline were used as recommended. Relaxation agents, with a low potential for histamine release, for example, veceronium, were used. All these precautions were helpful in providing the child with a safe dental treatment with minimum risk.

Dental considerations

Figure 3b. Deep carious lesions involving the left mandibular teeth.

form of behaviour management was deemed necessary. Previous reports had presented a number of complications in patients with mastocytosis undergoing GA and include anaphylaxis, cardiovascular collapse, bleeding and even death (Borgeat and Ruetsch,1998; Auvray et al., 2001). Pre-medication, to control anxiety, is generally recommended before general anaesthesia in children. However, in children suffering from mastocytosis it is imperative to provide it since anxiety increases mast cell activity. Intubations should be performed with special care so as not to bruise or to provoke bleeding, or skin irritation. The patient should be kept stable, avoiding low temperatures. It is recommended to provide preventive H1 and H2 blockers and to have IV adrenaline ready to use in the case of emergency. Drugs that are directly or indirectly associated with mast cell degranulation (including atropine

Primary and permanent teeth were restored with resin bonded composite restorations, pulpotomies and stainless steel crowns. Extraction of primary molars was indicated, since haemostasis of the pulp was not achieved after pulp exposure due to deep caries (Figure 4). The reason for the bleeding can be attributed to heparin release from mast cells, or the status of the dental pulp. However, no bleeding problems were observed after extractions, and spontaneous haemostasis was observed after a normal time. Our dental findings were dissimilar to Nelson and SavelliCastillo (2002), who reported dental treatment performed in the dental chair without local anaesthesia. In the present case, pulp treatment and extractions were needed, and local anaesthesia was imperative. In addition the child was not cooperative, and nitrous-oxide sedation was insufficient to control the child’s behaviour. Meticulous oral hygiene instructions were given to the parents, including the need to use a fluoridated dentifrice daily to help to prevent caries and to brush in order to prevent gingivitis. The child was scheduled for periodic follow up examinations.

Conclusion The present case describes the general and oral manifestations in a 6-year-old, uncooperative boy who suffered from mastocytosis, and who needed full mouth restorative treatment. The importance of a multidisciplinary approach is

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emphasised: the roles of the paediatrician, the anaesthesiologist and the paediatric dentist were crucial in the planning and performance of the dental treatment.

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Metcalfe DD. Regulation of normal and neoplastic human mast cell development in mastocytosis. Trans Am Clin Climatol Assoc 2005; 116: 185–203. Nelson LP, Savelli-Castillo I. Dental management of a pediatric patient with mastocytosis: a case report. Pediatr Dent 2002; 24: 343– 346. Valent P, Akin C, Sperr W et al. Mastocytosis: Pathology, genetics, and current options for therapy. Leuk Lymphoma 2005; 46: 35– 48. Worobec AS, Semere T, Nagata H et al. Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis. Cancer 1998; 83: 2120–2129.

Address for correspondence: Dr. Diana Ram Department of Paediatric Dentistry The Hebrew University-Hadassah School of Dental Medicine P.O.B 12272 Jerusalem 91120, Israel Email: [email protected]