O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

ABSTRACT The aim of this study was the prevalence and severity of oral dis- eases in patients with Shwachman- Diamond syndrome SDS. Thirty-five persons with SDS were compared to 20 healthy controls. A cross-sectional survey was carried out using self-report- ing questionnaires and dental radiographs collected from the subjects and their dentists. Overall, oral diseases were more prevalent among subjects with SDS when compared to controls (p<O.OOl). Persons with SDS also had more caries in both primary QxO.03) and permanent dentitions (p<O.Ol), and also had delayed dental development @<0.04). Oral soft tissue pathoses, such as recurrent oral ulcerations @<O.OO) and gingival bleeding upon brushing @<O.OO), were significantly more preva- lent in subjects with SDS. Pain on eating was also more frequent amongst persons with SDS @<0.008) and was often asso- ciated with oral ulcerati . In conclusion, based on self- subject and dentist questionnaires, dis- eases of oral hard and soft tissues were more prevalent and severe in persons with SDS when compared with healthy controls.

Prevalence of oral diseases in Shwachman-Diamond syndrome William Ho, BSc DDS;' Chrisovalantou Cheretakis, DDS;' Peter Durie, MD, FRCP(C);3 Gajanan Kulkarni, BDS, LLB, MSc, PhD, FRCD(C1;' Michael Glogauer, DDS, PhD2'

'Department of Pediatric Dentistry, Faculty of Dentistry, University of Toronto, Ontario, Canada; 'CIHR Group in Matrix Dynamics, University of Toronto; 3Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto. *Corresponding author E-mail: michael.glogauer@utoronto.ca

Spec Care Dentist 27(2): 52-8, 2007

I n t r o d u c t i o n Shwachman-Diamond syndrome (SDS, OMIM #260400)' is a rare multi-system disor- der mainly characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow dysfunction.' ' Segregation analysis suggests an autosomal recessive inheritance pattern with no racial or gender predilections.' The Shwachman-Bodian- Diamond syndrome gene (SBDS) linked to this disease entity was recently mapped.H

Within the first few months of life, steatorrhea and failure to thrive are among the most common symptoms which suggest a diagnosis of SDS.',' Excessive fecal fat loss, low levels of pancreatic enzymes and abnormal blood values, most often neutropenia, suggest a diagnosis of the syndrome.* Hematological defects secondary to bone marrow hypoplasia and maturation arrest of the myeloid lineage lead to low neutrophil counts or neutropenia in almost all patients diagnosed with SDS.' It has been shown that neutrophils in patients with SDS have inherent chemotaxis and motility defects,'J thus making these patients susceptible to infections even when their neutrophil counts are normal.' Patients with SDS may also suffer from thrombocytopenia and anemia" and some show increased risk of developing myelodysplastic syndrome which may lead to acute myelogenous leukemia (AML).I2 Median life expectancy of patients with SDS is approximately 35 years, with recurrent infections and acute myeloid leukemia being the most common causes of death.l'

Current information regarding the oral problems associated with SDS has come from case reports or cross-sectional studies that focused on the underlying systemic conditions. These studies make brief com- ments about oral problems including canes and oral lesions found in patients with SDS.' 5 1 4 1 5 A detailed investigation is lacking regarding the oral health status among patients with SDS. This cross-sec- tional study was designed to determine the prevalence and severity of oral diseases in patients with SDS and if oral diseases con- tributed to their morbidity

M e t h o d s Study subjects Because SDS is an uncommon condition, a mail survey was used to include as many patients with SDS as possible across North America. The majority of North American patients diagnosed with the syndrome are registered in one or both of the following support groups: SDS Foundation (formerly SDS International) and SDS Following approval from the Medical and Scientific Advisory Board of SDSF, the

52 Spec Care Dentist 27(2) 2007

O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

Median age (range)

Male : female ratio

Research Committee of SDS Canada, and the Health Science Ethics Review Committee at the University of Toronto, mailing lists were obtained from the aforementioned organizations and kept confidential from the investigators. At the time of the study, genotype testing was not available. In order to fulfill the inclusion criteria, subjects must have been diagnosed with SDS and had symp- toms of exocrine pancreatic dysfunction and congenital neutropenia confirmed by a physician. Pancreatic dysfunction was defined as a decreased exocrine enzyme secretion from less than 2% to approxi- mately 10% to 14% of the reference range? Neutropenia was defined by an absolute neutrophil count equal to or less than 1.5 x lO”/L.’* Supporting infor- mation was also collected when necessary to establish eligibility.’H All subjects with SDS were neutropenic; 37% were diagnosed with cyclic neutropenia and 37% were diagnosed with chronic neutropenia. The remainder did not specify their neutropenic status. All of our subjects with SDS were otherwise disease-free. Forty-nine percent of sub- jects with SDS were taking pancreatic enzyme supplements with meals and half of them were also taking fat-soluble vita- min supplements. None of them were on systemic steroids while 17% required G- CSF (granulocyte colony-stimulating factor) treatment. Daily prophylactic antibiotics or monthly IgG infusions were necessary for 14% of subjects with SDS. One person used aminocaproic acid for severe nose bleeds and 20% of the subjects with SDS were taking gastric acid inhibitors.

A total of 35 subjects with SDS and 20 healthy controls from 32 families par- ticipated in the study. No controls were available from one family with two affected siblings and 1 1 families where the child with SDS was an only child. Siblings who did not have SDS served as controls and received identical packages. Single-child families were encouraged to invite age-matched healthy neighbors to serve as controls. One family, which had two children diagnosed with SDS, invited two healthy age-matched neighbors to participate. Among the remaining 16

8.8 (1.7 - 39.6) years 9.5 (2 - 38.3) years

1.2: 1 1.5: 1

Pancreatic supplements

Fat-soluble supplements (A, D, E, K)

49 yo 0 Yo

26% 0%

I Neutropenia I 100% I 0% I Care provided by pediatric dentists

Dental insurance coverage

48% 46%

85% 71 %

Dental treatment cost was a concern 7% 31 % I I I families with two children, healthy sib- lings of children with SDS were available as controls. The two families with three children each had two children with SDS and one healthy sibling. Age distribu- tions of the group with SDS and the control groups were both positively skewed. Mean ages were 11.3k8.5 and 11.5k8.2 years, respectively. Racial back- ground information was not available from six subjects with SDS and two con- trols. Otherwise, all participants were Caucasian except for one pair with a mixed Asian and Caucasian background (Table 1).

Consent and institutional a pprova I Descriptions of the potential benefits and risks of participating in the study were included in each mail package. Parents of subjects younger than 16 years of age provided consent and completed the questionnaires on behalf of their chil- dren. Subjects between 7 and 16 years of age were required to sign assent forms. Those who had reached the age of 16 consented to participate and completed the questionnaires themselves. Prior to initiating the study, approval was granted by the Medical and Scientific Advisory Board of SDSF, the Research Committee of SDS Canada, and the Health Science Ethics Review Committee at the University of Toronto.

Questionnaires Questionnaires were prepared at the University of Toronto and distributed by the support groups to the families of sub- jects with SDS. Each questionnaire

package contained two versions of the questionnaire: one to be completed by the subject, and the other to be com- pleted by the subject’s dentist. The subject’s questionnaire consisted of three sections. The first part collected demo- graphic information such as age, gender, and racial background. The second part inquired about medical history with spe- cific questions regarding pancreatic and hematologic abnormalities. Subjects were also asked if they had previously taken granulocyte colony-stimulating factor (G-CSF), steroids, gamma globulin (IgG) or other supplements and medications to treat symptoms of SDS. The final section of the questionnaire inquired about the oral health status from the subject’s or the parent’s perspective.

ticipant’s dentist was asked to identify his or her clinical specialty Universal classifi- cation systems for primary and permanent dentitions were used on the dentists’ ques- tionnaires prepared for members of SDSF: The FDI system was used on forms sent out to members of SDS Canada. [The FDl system uses a two-digit numbering system in which the first number represents a tooth‘s quadrant and the second number represents the number of the tooth from the midline of the face. For permanent teeth, the upper right teeth begin with the number “1”. The upper left teeth begin with the number “2”. The lower left teeth begin with the number “3”. The lower right teeth begin with the number “4. For primary teeth, the sequence of numbers goes 5, 6, 7, and 8 for the teeth in the upper left, upper right, lower right, and lower left respectively] Dentists were

In the dentists’ questionnaires, the par-

Ho et a / Spec Care Dentist 27(2) 2007 53

O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

dmft

dmft/t

Primary dentition caries d .f . =30

DMFT Permanent dentition caries

DMFF/T d.f.=28

asked to identify which teeth were mobile, dysplastic, intrinsically stained or congeni- tally missing. Signs of premature or delayed eruption or exfoliation of primary and permanent teeth and probing depth of permanent first molars were also noted. The dentist’s questionnaire was specifically designed to reveal the current state as well as the history of dental disease. Carious activity in primary and permanent denti- tions was measured by dmft and DMFT scores, respectively. The scores for each individual were calculated using infornia- tion provided In the subject’s and dentist‘s questionnaires. Scores were verified when possible with dental radiographs sent to us from the dentist, with the patient’s con- sent. All radiographs in question were of good quality and thus easily interpreted by a single examiner (WH). Congenitally missing teeth, exfoliated primary teeth, and teeth that were extracted for reasons other than caries did not contribute to the dmft or DMFT scores. One of the inherent flaws with dmft and DMFT measurements is that the scores may increase with age, as more teeth are susceptible to caries. The total number of erupted primary and per- manent teeth constantly changes until 17 to 21 years of age. In order to account for such dynamics, calibration was necessary Raw scores (dmft and DMFT) were respec- tively divided by the total number of primary and permanent teeth that were once or still present in the oral cavity (dmft/t and DMFTR). All forms were returned to our department at the University of Toronto.

5.3 * 5.9 1.8 2.4 -2.39, 0.024 (-1.84, 0.075)’

0.27 * 0.29 0.09 * 0.12 -2.39, 0.024 (-2.33, 0.027)’

3.0 2 4.3 0.25 2 0.46 -2.93, 0.01 (-2.98, 0.01)’

0.12 2 0.15 0.015 2 0.030 -3.09, 0.005 (-3.10, 0.005)’

Statist i ca I ana I ys i s Data were compiled and analyzed using SPSS@ 10.1 for Windows@.’” Differences between means were assessed using stu- dents’ t-test. Fisher Exact tests and chi-square analyses were used to assess differences in proportions. Significance level was set at 0.05.

Delayed dental development

Results

_ _ _ ~ ~~~~~~ ~

33% (9/27) 0% (0/11) 0.038b

Dental history Siblings within each family visited the same dentist except for one pair of adult participants. Three dentists indicated

I SDS I Control I t-tests, p-values I I I

I I SDS 1 Control I p-values I IRecurrent aphthous ulceration I 65% (17/261’ I 0% (0/181’ I 0.000 I IGingival bleeding I 58% (151261’ I 0% (0/171’ I 0.000 I lPain on eating I 44% (8/18)’ I 0% (0/151’ I 0.008 I laproportion of the group with the soft tissue pathosis.

Figure 1. Idiopathic internal resorption in primary molars from two siblings with SDS from the same family who had three children. This was not evident in the eldest healthy sibling. Perforation at the cemento-enamel junction resulted in pulpal exposure. Both teeth eventually became abscessed and were extracted.

that they prescribed prophylactic antibi- otics prior to dental treatment for their persons with SDS. Comprehensive dental treatment under general anesthesia was necessary for one subject with SDS (age 18 months). Another person with SDS (age 39.6 years) had had frequent dental abscesses, which required multiple hos- pitalizations; the teeth were discolored due to antibiotics used during early childhood. One subject with SDS (age 7.9 years) had severe loss of attachment around all first permanent molars and required periodontal surgery. Overall, 83% (29/35) of the study’s persons with SDS reported having various oral diseases which included the oral hard and soft

tissue pathoses summarized in Tables 2 and 3. Six children with SDS (age 1.7 to 7.9 years) from different families reported that they had no oral pathoses. None of them encountered difficulties eating. Significantly fewer controls reported the presence of oral diseases (35%, p<o.oOl).

Oral hard tissue diseases: dental caries Using information provided by the sub- jects, their dentists and dental radiographs, it was possible to calculate dmft for the primary dentition of the 32 participants (21 SDS; 11 controls) and DMFT for the permanent dentition for

54 Spec Care Dent ist 27(2) 2007 Oral d isease and Shwachman-Diamond syndrome

O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

Recurrent aphthous ulceration

Gingival bleeding

30 participants (22 SDS; 8 controls). These scores revealed that persons with SDS were significantly more affected by dental caries than control subjects in both dentitions (Table 2). 78% (719)‘ 0% (0/8Ib 0.002

62% (518)” 22% (2/9Ib 0.15 Other dental anomalies Most dentists of persons with SDS reported delayed dental development in their subjects while all of the dentists treating the control subjects deemed dental development to be normal (Table 2). None of the participants reported problems regarding premature exfoliation or precocious eruption. Two dentists reported congenitally missing bilateral maxillary second premolars in their sub- jects with SDS and one of these persons also had congenitally missing bilateral maxillary permanent lateral incisors as well as transposed permanent canine and first premolar in the maxillary left quad- rant. Three dentists confirmed the diagnosis of dysplastic enamel in subjects with SDS. In the healthy control popula- tion, two control siblings of subjects with SDS from one family with three children had idiopathic internal resorption that resulted in early extraction due to infec- tion (Figure 1).

Oral soft tissue diseases None of the control subjects reported any oral soft tissue pathoses. In contrast, 65% of persons with SDS reported expe- riencing recurrent oral ulcerations. Among them, 41% reported having lesions more than four times a year (Figure 2). Also, 58% of subjects with SDS reported encountering gingival bleeding upon brushing; and this occurred more than twice a week among half of those subjects (Figure 3). Forty- four percent of subjects with SDS reported experiencing pain on eating compared to none of the controls. Pain was significantly associated with recur- rent oral ulcerations but not gingival bleeding (Table 4). In fact, subjects with SDS who did not report recurrent oral ulcerations also did not report feeling pain while eating.

I I Pain I No pain I p-values I

~ ~~ ~ ~~ ~ ~

aProportion of subjects with the soft tissue pathosis who also experienced pain on eating. I bProportion of subjects without the soft tissue pathosis who did not experience pain on eating.

Discussion Based on the self-reported findings from this cross-sectional study which were supported by dental reports, a significant burden of oral diseases in persons included dental caries, delayed dental development, recurrent ulcerations and gingivitis. This study also showed that oral diseases contributed to morbidity in persons with SDS.

Oral health is integral to general health and can have a significant impact on overall well-being.’@ In 2000, the Surgeon General of the United States emphasized that oral health means more than just healthy teeth and that individu- als with special healthcare needs are particularly susceptible to oral diseases.’” SDS was first recognized 40 years ago.””’ Yet, very few reports exist which profile the oral health problems of these per- sons. The first International SDS Family Conference held in 2001 identified dental disorders as one of the many issues that required further description and understanding in persons with SDS.z’

Dental caries Dental caries is the single most common chronic childhood disease.?” Bodian et uI,,$ Aggett et al.,’ and Dror et al.“ noticed severe caries in their subjects with SDS but did not elaborate. Our study verified that caries was more prevalent and more severe among sub- jects with SDS relative to healthy controls. Etiology of dental caries is multi-factorial. Exocrine pancreatic insufficiency had never been linked to any dental diseases. It has been suggested” that cyclic neutropenia might play a role in caries, yet strong evidence regarding neutropenia as a risk factor is still lacking. Persons with SDS are prone to infections and their frequent exposure

to cariogenic antibiotic syrups might be contributing to their risk of caries.?.” Discomfort from oral ulcerations super- imposed on systemic illness may negatively influence meticulous oral hygiene so that removal of cariogenic food debris and bacteria would be inade- quate.” Drug-induced xerostomia interferes with remineralization and therefore presents another risk factor. Drugs taken by some subjects with SDS in this study included anti-ulcerheflux medications such as cisapride (anti- emetic), lansoprazole and omeprazole (gastric acid secretion inhibitors), and decongestants such as chlorpheniramine and phenylephrine, which can all lead to dry mouth.25 However, other reported medications such as cimetidine, famoti- dine and ranitidine (histamine H, antagonists), clonidine (anti-hyperten- sive) and venlafaxine (antidepressant) do not have such severe side effectsz5

Other dental anomalies Abnormal development of the dentition was not evident in the control group but delayed dental development was reported in 33% of persons with SDS. One of 21 persons with SDS reported by Aggett’ also had delayed exfoliatioderuption. The skeletal age of subjects with SDS was often delayed and might be related to these findings.2J’,2h.27 Prior to diagnosis and supplementation with pancreatic enzymes and vitamins, insufficient caloric intake might also play a role in delayed

Anomalies such as hypodontia, hyper- dontia, transposition and impaction of teeth only occurred sporadically as isolated incidents among persons with SDS and were unlikely manifestations of the syn- drome. Discolored teeth reported by one of the adult subjects with SDS were probably

Ho et a / Spec Care Dent ist 27(2) 2007 55

O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

caused by intrinsic tetracycline staining when the permanent teeth were still devel- oping during early childhood.2y In keeping with findings from Aggett’ and Ginzberg,’ three dentists in the current study reported that their subjects with SDS had dysplastic enamel. Since clinical photographs were not available from any of the studies, it was impossible to determine whether the abnormal dental morphology was actually a manifestation of fluorosis or amelogene- sis imperfe~ta.~” The possibility of Turner’s hypoplasia secondary to traumatized or infected deciduous teeth also could not be ruled Idiopathic internal resorption occurred in two healthy control siblings in the same family. In both children sound second primary molars were affected and resulted in early extraction and insertion of space maintainer.

Recurrent oral ulceration Neutropenia-associated aphthous stom- atitis has been well documented.”-” Burke et al.’ first noted recurrent ulcera- tive stomatitis in two of their patients with SDS. Our study identified that such soft tissue pathosis was reported by two- thirds of subjects with SDS while none of the healthy controls reported any prob- lems (Figure 2). The majority of our subjects with SDS reported being plagued by ulcers more than four times per year. In cyclic neutropenia, oral ulcerations occur concurrently with a low circulating neutrophil count during each cycle.” This may be the only manifestation but the role of neutrophils in aphthae is still not well understood. Resear~h’~ has sug- gested that these cells might be the cause of breakdown of the mucosal epithelium. Another study” found that the concen- trated presence of neutrophils at the center of ulcerations was only responsi- ble for perpetuation of the lesions. Stress, trauma, bacterial or viral infections, mal- nutrition such as vitamin B or folate deficiency, and immunodeficiency are among other suggested causes.”

Gingivitis More than half of subjects with SDS reported gingival bleeding upon brushing their teeth (Figure 3) . Belkind-Gerson et al.” reported swollen and bleeding gingiva

<2Xlvr 2-3Xlyr

^ A ,

>4X/yr 41%

Figure 2. Frequency of recurrent oral ulcera- tion among subjects with SDS. Seventeen of 26 subjects with SDS had recurrent oral ulcer- ation. Frequency of occurrence among these 17 subjects is displayed in the pie chart. Most (41 %f of the subjects reported having ulcers more than four times a year. The most proba- ble underlying etiology is neutropenia.

in a subject with SDS. Plaque-induced gingivitis is the most common cause of gingival hemorrhage upon mechanical irritation. Although oral hygiene was not assessed, the reported bleeding was most likely a reflection of poor gingival health. Long-term antibiotic usage can alter the intestinal microflora, leading to vitamin K deficiency which in turn results in abnor- mal coagulation.” Coagulopathies may therefore present as gingival hemorrhage. This might be the cause in patients with SDS who have thrombocytopenia. In our study, subjects with pancreatic insuffi- ciency were all treated with enzymes and vitamin supplements only, thus medica- tion to treat pancreatic insufficiency was unlikely to be the cause of gingivitis.

Periodontal diseases The strong association between neutrope- nia and periodontal diseases has been well established.” l3 Most dentists associated with this study did not provide informa- tion regarding probing depths. Except for one child with SDS who had advanced periodontal bone loss which required sur- gical management, all the dentists who responded indicated that their patients had normal periodontal bone height. From the available dental radiographs, alveolar bone level appeared to be within normal limits when examined by WH. It has been proven that neutrophils of

>4Xlwk 0%

3-4XIwk - 27% a

Figure 3. Frequency of bleeding on brushing among subjects with SDS. Fifteen of 26 sub- jects with SDS encountered bleeding upon brushing. Frequency of occurrence among these 15 subjects is displayed in the pie chart. The bleeding occurred weekly and was mostly likely due to plaque-induced gingivitis, although thrombocytopenia could not be ruled out.

patients with SDS have chemotaxis and motility defects.” ’” Perhaps this defect serves as a protective factor. It is possible that when an insufficient number of neu- trophils is found in the gingival sulcus, this contributes to preventing excessive breakdown of connective tissue by neu- trophil lysozomal enzymes.”

Oral diseases and morbidity Dental infections and oral ulcerations are among the most common causes of mor- bidity in the craniofacial region.>’ Bodian et al.’ mentioned that one of their subjects with SDS had a poor appetite as a result of dental caries while Ginzberg’ reported that oral cellulitis and dental abscesses were among the most common infections in persons with SDS. Our subjects with SDS reported feeling pain significantly more often upon eating than healthy controls. This phenomenon was always associated with recurrent oral ulcerations. Pain from eating may lead to decreased food intake, malnutrition and poor overall health. Oral hygiene practices, eating, speaking, and sleeping could also be limited depending on the magnitude and duration of discom- fort from various oral diseases.z0~24 Persistent oral ulcerations also serve as a portal of entry for infectious organisms. Extensive dental caries and frequent severe odontogenic infections may require treat- ment in a hospital. Oral diseases can

56 Spec Care Dent ist 27 (2 ) 2 0 0 7 Ora / disease and Sh wa c hman - Dia m on d syndrome

O R A L D I S E A S E A N D S H W A C H M A N - D I A M O N D S Y N D R O M E

Aggett eta/.? 21 subjects, no control

Ginzberg et ab5 This study 88 subjects, 35 subjects, no control 20 controls

Dental caries

Dysplastic teeth

38% 83%

14% 10% 9%

(G%valbleedi& - I I I 58% I

Delayed dental development

Recurrent oral ulceration

5% 33%

65 %

significantly add to the existing morbidity already burdening patients with SDS.

Study limitations Prevalence and severity of oral diseases in SDS cannot be calculated in a cross- sectional survey design. Non-response bias might arise from persons not affected by oral diseases or by those who did not visit their dentists regularly. Conversely, persons with severe oral dis- eases might have already succumbed to complications from the syndrome (e.g. infections, leukemia, etc.). According to results from Table 2, 28 pairs would be required to carry out paired-analysis to achieve 80% power at 5% significance level.” In this study, the sample size was rather small due to the rarity of the con- dition studied. While only 20 controls were found after three years of data col- lection, this study does suggest the close association between oral diseases and SDS. Direct or indirect causal relation- ships remain to be established. For example, i t was unclear if the increased incidence of caries was due to neutrope- nia resulting from the syndrome or due to an altered diet or intake of sweetened medications. Understanding the underly- ing etiology would require dietary analyses as well as chair-side clinical oral examinations of subjects with SDS and their controls. Probing depth, caries risk factors such as oral hygiene, salivary bac- terial count and parental caries activities would need to be assessed.

Negative impact on eating

Dental management of patients with SDS Dental care is medically necessary for prevention, control and elimination of

44%

orofacial infection and pain.?” Management of patients with SDS can be challenging due to the complex underly- ing systemic as well as psychosocial issue^.'^^.'^ Oral health care should be pro- vided by pediatric dentists because of their specialized knowledge and increased awareness of the unique prob- lems associated with patients with special healthcare needs.” Since dental caries is a preventable infectious disease, parents and primary care physicians should also be educated about preven- tion. Parents need to have established comprehensive dental care for their chil- dren by the time they have reached 12 months of age.’“.’’ Recurrent oral ulcera- tions can be managed by coating agents such as Kaopectate, topical anesthetic elixirs/sprays/gels, diphenhydramine solutions or benzydamine rinse^."^^' Topical steroids, while useful for healthy patients in the treatment of oral ulcers, may predispose patients with neutrope- nia to opportunistic infections.

Prior to dental treatment either at chair-side or under general anesthesia, consultation with a hematologist should be arranged. Updated complete and differ- ential blood counts assist in the determination of the need for peri-opera- tive antibiotic coverage, blood, platelets or vitamin K infusion, and hospitalization.

Patients with SDS are also predis- posed to myeloid dysplasia and AML (acute myelogenous leukemia).” Gingival enlargement or spontaneous gingival bleeding may be the first signs of AML. Although elective dental treat- ment may have to be postponed,”,’” a dental consultation should be arranged prior to chemotherapy and/or bone

marrow transplantation. Aggressive dental treatment may be necessary to remove potential sources of odontogenic infection.”’” Upon successful transplan- tation, immunosuppressive drugs for graft versus host disease (e.g. cyclosporine) can cause gingival hyper- plasia in approximately 30% of the patients.J’ The need for oral hygiene is imperative.”

C o n c l u s i o n s This study showed that the following oral diseases were associated with SDS: (Table 5)

dental caries delayed dental development recurrent oral ulcerations gingivitis

general health and well-being of the sub- jects with SDS. Upon diagnosis of the syndrome, consultation with a pediatric dentist is highly recommended.

Oral diseases had an impact on the

A c k n o w l e d g e m e n t s Funding for the study was provided by the SDS Foundation (formerly SDS International) and SDS Canada. Participants in the study were not com- pensated by any means. The authors declare that there was no conflict of interest but would like to thank all patients and their families who partici- pated in the study as well as the many members of the SDS Foundation and SDS Canada who made this survey project possible. Chrisovalantou Cheretakis is supported by a CIHR Clinical Research Initiative Fellowship and by the CIHR Strategic Training Program, Cell Signaling in Mucosal Inflammation and Pain (STP-52877). Dr. Glogauer is a Canadian Institutes of Health Research New Investigator Award Recipient.

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58 Spec Care Dentist 27(2) 2007 Oral disease and Shwachman-Diamond syndrome