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Medically compromised children

Kerrod B Hallett, Sherene Alexander, Meredith Wilson, Craig Munns, Angus C Cameron and Richard P Widmer

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Introduction

Comprehensive dental care of a medically compromised child requires consideration of their underlying systemic condition and coordination of their dental treatment with their medical consultant. Although dental problems are common in this group, their oral health is overlooked frequently by the medical profession. The term used to identify this particular group, ‘medically compromised children’, has been replaced recently by the more general term ‘children with special needs’. However, the older term is still relevant because it reminds the dentist that these children often have medical conditions that can affect dental treatment or that they can present with specific oral manifestations of a systemic disease. This chapter discusses the common paediatric medical conditions that require consideration in the provision of optimal dental treatment. The prevention of oral diseases is important in children with chronic medical problems (Figure 12.1), as oral complications can severely compromise a child’s medical management and overall prognosis.

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Figure 12.1 (A) Children with medical problems may have conditions with a dental manifestation. This child has osteogenesis imperfecta – or they may present with a medical comorbidity that complicates their general dental care. (B) Not all children with medical problems require hospital admission, although treatment of such patients is often challenging. Mobile dental equipment is invaluable in providing quality dental care. The majority of hospital inpatients are treated in the dental surgery and usually only those who may be in traction or in intensive care units require bedside treatment.

Cardiology

Congenital heart disease

Congenital heart disease (CHD) has an incidence of approximately 8–10 cases per 1000 live births and represents the largest group of paediatric cardiovascular diseases. Although most lesions occur individually, several form major components of syndromes or chromosomal disorders such as Down syndrome (trisomy 21) (see Figure 12.2A) and Turner syndrome (45, X chromosome) with over 40% of children being affected. However, in the majority of cases, no cause can be determined and a multifactorial aetiology is often assumed. Known risk factors associated with CHD include maternal rubella, diabetes, alcoholism, irradiation and drugs such as thalidomide, phenytoin sodium (Dilantin) and warfarin sodium (Coumadin). Turbulent blood flow is caused by structural abnormalities of the heart anatomy and presents clinically as an audible murmur. The degree of clinical morbidity is determined by the haemodynamics of the lesion. Congenital heart disease can be classified into acyanotic (shunt or stenotic) and cyanotic lesions depending on clinical presentation. Eight common conditions account for 85% of all cases.

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Figure 12.2 (A) Intra-oral photograph of a child with complex cyanotic cardiac disease associated with trisomy 21. Note the cyanosis of the gingival tissues. Of importance is to note that he has no dental disease. His oral hygiene is exceptional and there is no caries. Treatment would have been extremely difficult due to his intellectual disability. (B) Clubbing of the fingers associated with complex cyanotic cardiac disease. The nail beds also show cyanosis.

Cyanotic conditions (Figure 12.2)

All cyanotic conditions exhibit right-to-left shunting of desaturated blood. Cyanotic defects become clinically evident when 50 g/L of desaturated haemoglobin is present in peripheral arterial blood. Infants with mild cyanosis may be pink at rest but become very blue during crying or physical exertion. Children with cyanotic defects are at significant risk for desaturation during general anaesthesia and preoperative consultation with the paediatric cardiologist and anaesthetist is essential.

The most common cyanotic lesions are:

• Tetralogy of Fallot – which includes a VSD, pulmonary stenosis at valve or sub-valve levels, a large overriding aorta and right ventricular hypertrophy.

• Transposition of great vessels – when the aorta exits the heart from the right side and the pulmonary artery exits from the left. Although the internal heart anatomy is normal, the systemic blood circulation cannot be resaturated with oxygen and immediate management of transposition by opening the ductus arteriosus and corrective surgery is required.

• Eisenmenger syndrome – this refers to cyanosis from any right-to-left shunt caused by increased pulmonary resistance through a VSD or PDA.

• Tricuspid atresia – due to absent tricuspid valve and may present with an absent right ventricle and pulmonary valve. The pulmonary circulation is maintained through a PDA in the neonate.

• Pulmonary atresia – which is similar to tricuspid atresia except that the tricuspid valve is patent.

Other cardiovascular diseases

Other common paediatric cardiovascular disorders include cardiomyopathies such as myocardial disease and pericardial disease, cardiac arrhythmia, infective endocarditis and rheumatic heart disease (RHD). Both CHD and RHD can predispose the internal lining of the heart to bacterial or fungal infection (infective endocarditis) and lead to the formation of friable vegetations of blood cells and organisms. Vegetations may embolize and cause renal, pulmonary or myocardial infarcts or cerebrovascular accidents. Streptococcus viridans, a common commensal organism in the oral cavity, is most frequently responsible for chronic infective endocarditis, whereas Staphylococcus aureus is often implicated in the acute fulminating form of infective endocarditis.

Dental management

Several important principles need to be followed when managing children with cardiac disease. Transient bacteraemia can occur following invasive dental procedures and potentially cause infective endocarditis in a susceptible patient. Therefore, all children with CHD or previous RHD require antibiotic prophylaxis to reduce the risk of infective endocarditis (see Appendix E). Those children who have been previously taking long-term antibiotics should be prescribed an alternative medication as per the protocol to avoid development of resistant oral organisms. In addition, a preoperative oral antiseptic mouthwash, such as 0.2% chlorhexidine gluconate, is recommended to reduce the oral bacterial counts.

Children with CHD have a higher prevalence of enamel anomalies in the primary dentition and concomitant risk of early childhood caries. Some cardiac medications may contain up to 30% sucrose and dietary prescription with high-caloric supplements (Polyjoule) further potentiate caries risk. Meticulous oral hygiene and preventive dental care, such as fissure sealants and topical fluoride therapy is recommended to reduce the risk of dental caries in susceptible children.

Dental disease in children with cardiac disorders can seriously complicate their medical management. Children with advanced cardiovascular disease should receive only palliative dental care until their medical condition has been stabilized. Aggressive treatment of pulpally involved primary teeth is recommended. Pulpotomy or pulpectomy is contraindicated in these children due to the possibility of subsequent chronic bacteraemia. Although routine treatment in the dental surgery environment is possible, it is often preferable to manage children with multiple carious teeth under general anaesthesia in the hospital environment. This protocol allows completion of treatment with one invasive procedure and negates the risk of infective endocarditis with further operative procedures. If multiple visits are planned, there is a need to prescribe alternative antibiotics or wait for a month between appointments to reduce bacterial resistance.

A thorough preoperative assessment of the child’s regular medication (including anticoagulants, antiarrhythmics, and antihypertensives) is essential to avoid any potential drug interactions during treatment. There is no contraindication to the use of vasoconstrictors in local anaesthetic solutions. If conscious sedation is used, vital signs and oxygen saturation during the procedure should be carefully monitored. Avoid the use of electrosurgery, electronic pulp testers and ultrasonic cleaning devices in children with cardiac pacemakers, in case of potential interference. Some common impediments are non-compliance with oral hygiene and dietary advice, postoperative infection and bleeding.

Haematology

Disorders of haemostasis

Primary haemostasis is initiated after injury to a blood vessel with the formation of a primary platelet plug. This process is mediated by interactions between the platelets and coagulation factors in the plasma and the vessel wall. Secondary haemostasis or coagulation is also triggered by the initial injury and reaches its greatest intensity after the primary platelet plug is formed. Fibrin deposition provides the framework for the formation of a stable blood clot.

Prolonged bleeding can occur when either phase of haemostasis is disturbed. The clinical manifestations of a haemostasis disorder vary depending on the phase affected. Defects in primary haemostasis generally result in bleeding from the skin or mucosal surfaces, with the development of petechiae and purpura (ecchymoses). These disorders include von Willebrand’s disease as well as defects in platelet function. In contrast, defects in secondary haemostasis, such as haemophilia, lead to bleeding that tends to be more deep-seated in muscles and joints. In both disorders, uncontrolled prolonged oral bleeding can occur from innocuous insults such as a tongue laceration or cheek biting.

Children with haemostasis disorders can be identified from a thorough medical history, examination and laboratory tests. Questions should reveal episodes of spontaneous bleeding or bruising; the occurrence of prolonged bleeding in other family members and prescription of anticoagulant medication. A physical examination of skin (unusual areas of bruising on the chest or back or bruising from lying on a toy), joints and oral mucosa should be undertaken for evidence of petechiae, ecchymoses and haematoma. If a haemostasis disorder is suspected, referral to a haematologist is recommended for evaluation and laboratory blood tests.

Classification

Platelet disorders

Platelet disorders can be either a deficiency (thrombocytopenia) or dysfunction.

Inherited coagulation disorders

Coagulation disorders result from a decrease in the amount of particular plasma factors in the coagulation cascade. The most common disorders are haemophilia A and von Willebrand’s disease, both manifesting a decrease in factor VIII levels. The factor VIII is produced by endothelial cells and is composed of two portions. The largest part of the molecule is the von Willebrand’s factor and is responsible for initial platelet aggregation. The factor VIII part of the complex and factor IX are responsible for activation of factor X in the intrinsic pathway of the coagulation cascade. Other disorders of coagulation include vitamin K deficiency, liver disease and disseminated intravascular coagulation usually from overwhelming (Gram-negative) infection.

Coagulation disorders are classified according to the defective plasma factor; the most common conditions are factor VIII (haemophilia A) and factor IX (haemophilia B or Christmas disease). von Willebrand’s disease occupies a unique position in that both platelet and factor VIII activity is decreased, therefore both bleeding time and APTT are prolonged.

Dental management

Dental management of children with suspected haemostasis disorders should begin with screening laboratory tests. If tests are abnormal, haematological consultation is required for a definitive diagnosis. Invasive dental procedures should be performed only after the extent of the problem has been determined. Extractions must never be performed without first consulting the haematologist. It is preferable to have platelet levels >80 × 109/L before extractions. Endodontic procedures may be preferable to extractions in order to avoid the need for platelet transfusion.

Medical management

1-Deamino (8-D-arginine) vasopressin (DDAVP)

• Can be used for people with mild haemophilia and those with von Willebrand’s disease.

• Can result in an up to two-fold release of factor VIII from endothelial cells – this is adequate if levels of factor VIII are >10% and the patient is responsive to DDAVP.

Post-surgical administration of antifibrinolytic agents such as tranexamic acid (Cyklokapron) 25 mg/kg loading dose and 15–20 mg/kg three times daily for 5–7 days is helpful in preventing clot lysis. During the time that antifibrinolytics are given, the parent and child should be instructed not to use straws, metal utensils, pacifiers or baby bottle teats.

Characteristically, haemophilia bleeds are delayed 12–24 h, as primary haemostasis is not impaired, and local pressure has little effect. It is worth noting that mild haemophilia can go undiagnosed. The APTT is not sensitive to detect mild deficiencies of FVIIIc and levels of FVIIIc 25–30 IU/dL can be associated with a normal APTT. In addition, FVIIIc values in mild haemophilia are temporarily increased (as occurs in unaffected persons) by stress, exercise and bleeding. If there is a convincing history of a bleeding tendency always do a specific factor assay even if the initial screening tests are normal.

The normal regimen for DDAVP is 0.3 µg/kg intravenous infusion over 1 h before surgery followed by tranexamic acid 15–20 mg/kg orally every 8 h for 7 days. After 9–12 h, if the FVIIIc levels are still low (50–60%), then the original dose of DDAVP may be repeated. If repeated doses are planned or required it is important to fluid restrict the patient and monitor electrolytes. Repeated doses of DDAVP may cause fluid retention and hyponatraemia. This regimen is useful in von Willebrand’s disease and children on renal dialysis.

Anticoagulant therapy

Management of children on anticoagulant therapy needs special consideration. Anticoagulants are usually prescribed for children with valvular heart disease and prosthetic valves to reduce the risk of remobilization. If extractions or surgery are required, it is necessary to decrease the clotting times to facilitate adequate coagulation but not to such an extent so as to cause emboli or clotting around the valves. The dental management of these children is also complicated by their congenital cardiac defect and antibiotics are required for prophylaxis against infective endocarditis.

Therapeutic drugs used

Children on anticoagulant therapy should stop taking warfarin 3–5 days prior to the surgery date. In those in whom there is a significant risk for thrombosis with sub-therapeutic warfarin level, parenteral anticoagulation may be necessary. This is generally achieved with enoxaparin sodium (Clexane) 1.5 mg/kg subcutaneously once daily (mane) via Insuflon. This drug is omitted on the morning of surgery. With the use of this regimen, the child may be admitted to hospital on the day of dental surgery. Warfarin is recommenced in normal dose on the evening of surgery. If further enoxaparin sodium prophylaxis is required, it should be given the morning after surgery and continued until the PT and international normalized ratio (INR) are therapeutic. Monitoring of enoxaparin sodium is rarely required. In emergency situations with prolonged bleeding from oral wounds post-surgery, following recommencement of warfarin, FFP (fresh frozen plasma) may also be of benefit.

Management of oral haemorrhage

Unexpected bleeding from the oral cavity can occur at any time. There may have been a slow ooze for several days or, in the other extreme, there may be a significant sudden oral bleed. Such bleeding can occur without warning and may not be associated with any prior investigative or operative work. As well, haemorrhage from the mouth can occur following such routine procedures as biopsy, restorative work or tooth extraction.

The initial management of such cases involves identifying the exact site of haemorrhage, controlling the bleeding and then preventing a recurrence. In the cases of haemorrhage from the mouth that has not been associated with any dental procedure, clinicians should take an accurate history of the bleeding, the duration, lost volume and any causative factors. Abnormal bleeding may occur around an erupting tooth, from an exfoliating tooth site or may be associated with physical and sexual child abuse or congenital vascular anomalies such as arteriovenous malformations. The possibility of a childhood malignancy should also be considered.

In cases of oral haemorrhage following dental procedures, the following steps should be taken (it is important to prevent or minimize bleeding in the first instance):

• A sensible limitation of surgical trauma.

• Digital compression of the alveolus after tooth extraction.

• Packing of the socket with a resorbable gel.

• Adequate suturing of extraction sites to help reduce postoperative complications.

• Pressure application to the surgical site with gauze packs.

• Construction of a removable splint is recommended following more extensive surgery.

• Written postoperative instructions to ensure adequate rest, avoidance of hard foods and early mouth rinsing.

• Prescription of non-aspirin medication are necessary to avoid any parent misunderstanding.

In cases of severe uncontrollable haemorrhage following tooth extraction that can occur due to arteriovenous malformations, remember that the best method of controlling the bleeding is to replant the extracted tooth back into the socket and suture it well.

Red cell disorders

Haemoglobinopathies

Thalassaemia

The haemoglobinopathies are a group of genetic disorders involving the globin chains of the haemoglobin (Hb) complex. These diseases comprise two main groups: the structural haemoglobinopathies, resulting in abnormal globins (HbE, HbS) and the thalassaemias. The thalassaemias represent a group of autosomal recessive disorders, common in patients from the Mediterranean, North Africa, the Middle East, India and Central Asia, expressing mutations of genes responsible for the production of any of the haemoglobin chains.

Haemoglobin is a tetrameric protein comprising four globin protein subunits. Adult blood contains haemoglobin A (HbA), comprised of two α-chains and two β-chains and a small amount of haemoglobin A2 (HbA2) comprised of two α-chains and two δ-chains. Children also produce fetal haemoglobin (HbF – two α-chains and two γ-chains), which has a much higher oxygen affinity. Fetal haemoglobin levels decrease after 6 months of age from around 70% at birth to trace amounts in adulthood.

α-Thalassaemia – is caused by deletions or mutations of the four alpha globin genes on chromosome 16. One to four genes may be affected, resulting in a relative overproduction of β-chains. Homozygous α-zero thalassaemia (four alpha globin genes deleted) is incompatible with life, while carriers (1–2 gene deletions) have no clinical symptoms. Children with HbH disease (three alpha genes deleted/abnormal) may have mild anaemia or a transfusion dependent anaemia.

β-Thalassaemia – Of more clinical significance is homozygous β-thalassaemia major (Cooley’s anaemia). Due to the absence of the β-chain, there is a compensatory increased production of HbA2 and HbF. As erythropoiesis is inadequate, the bone marrow is reactive and there is compensatory intermedullary haemopoiesis in the maxilla and diploe of the skull. There may be severe haemolytic anaemia with marked hepatosplenomegaly and failure to thrive. Those children with sickle/β-thalassaemia show evidence of vascular thrombosis with ischaemia to organs, especially bones.

Due to maxillary and zygomatic overgrowth there is often a severe Class II Division 1 malocclusion with separation of teeth and widening of the periodontal ligament space. Lateral skull radiographs demonstrate a ‘hair on end’ appearance. Children are given regular packed red cell hypertransfusions until the haemoglobin rises to 140–150 g/L and desferrioxamine, an iron-chelating agent, to increase iron excretion. When excessive haemosiderosis in the spleen adds significantly to the haemolysis rate, elective splenectomy is performed.

Immunodeficiency

Immunodeficiency may be caused by quantitative or qualitative defects in neutrophils, primary immunodeficiencies, involving T cells, B cells, complement or combined defects and secondary immunodeficiency or acquired disorders.

Dental management

Regular review of the developing dentition, gingivae and mucosa and the institution of a preventive programme are essential for maintenance of healthy hard and soft tissues. Elimination of any potential oral focus of infection during the course of medical treatment is the primary objective.

The underlying deficiency must be fully assessed and the likelihood of oral complications endangering the child’s medical status should be evaluated. An individual risk–benefit assessment of any oral lesion must be considered with regard to the overall management plan.

A decision whether to extract or maintain carious teeth and exfoliating primary teeth must be based on the worst case scenario during the immunodeficiency period. If a carious lesion cannot be stabilized with an adequate interim restoration, then extraction is the preferred treatment. In a case being prepared for bone marrow transplantation, all mobile primary teeth should be removed at least 2 weeks prior to the conditioning phase.

Thorough dental scaling and prophylaxis and the provision of custom trays for delivery of medication (antiseptic or fluoride gels) prior to commencement of head and neck radiotherapy is also recommended to prevent oral sepsis and radiation-induced dental caries.

Prophylactic antimicrobials specific for commensal oral organisms determined from culture and sensitivity tests are indicated during the course of medical treatment. Biopsy specimens may assist the diagnostic process. The antimicrobial protocol may include appropriate antibiotics (amoxicillin trihydrate and ampicillin, vancomycin), acyclovir sodium if HSV-positive, ganciclovir if cytomegalovirus-positive, antifungals (topical nystatin and amphotericin B) and twice daily 0.2% chlorhexidine gluconate (Curasept) mouthwashes during the active therapy phase.

Acquired immunodeficiency syndrome (AIDS)/HIV

HIV infection has been identified in increasing numbers of children with otherwise unexplained immune deficiency and opportunistic infections of the type found in adults with acquired immune deficiency syndrome (AIDS). For the limited purposes of epidemiological surveillance, the Centers for Disease Control (CDC) characterizes a case of paediatric HIV infection as a reliably diagnosed disease in children that is at least moderately indicative of underlying cellular immunodeficiency, and with which no known cause of underlying cellular immunodeficiency or any other reduced resistance is reported to be associated.

Transmission

The main transmission media are body fluid, such as blood and semen. Saliva contains low and inconsistent levels of the HIV virus and is unlikely to provide a significant mode of transmission. Consequently, the two major routes of transmission in children are vertical (from an infected mother) and from blood products, with children with haemophilia being most at risk. Vertical transmission rates are up to 39% and occur before, during or after birth. Infection from breast-feeding may be up to 29%.

Oral manifestations (Figure 12.6)

Oral lesions are often early warning signs of HIV infection. Common disorders may manifest in different ways in the presence of HIV. In children, the most common lesions are:

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Figure 12.6 Severe oral ulceration in a child in the terminal stages of HIV/AIDS. The ulceration was most likely due to disseminated HSV infection, to which the child succumbed 7 days after this photograph was taken.

Candidosis

The most common oral lesion in HIV infection is acute pseudomembranous candidiasis. It is an early lesion and suggests the presence of other opportunistic infections. The severity of the candida infection may be related to the T4/T8 ratio and occurs when CD4 counts are <300/mL. Oesophageal candidiasis occurs when CD4 counts drop below 100/mL. Fungal infections can be related to reduced salivary flow and S-IgA. It responds well to treatment with systemic antifungals and an improvement in oral hygiene.

Ulceration

Recurrent herpes simplex infections are frequent and are typically intra-oral and circum-oral. Other parts of the body may also be affected. Aphthous-type ulcers are persistent and very common in children. Treatment is palliative with adequate hydration, analgesia and the use of Diflamm-C mouth rinses.

Atypical gingivitis

HIV-related gingivitis manifests as red erythematous gingival tissues and can extend to the free gingival margin. There is often spontaneous gingival haemorrhage and petechiae within the gingival margin, either localized or generalized. Consideration must be given to a fungal component. Treatment involves improved tooth brushing and flossing and the use of daily 0.2% chlorhexidine gluconate (Curasept) mouthwashes and gels.

Salivary gland enlargement

Parotitis or HIV associated parotid gland disease (HIV-PGD) occurs more frequently in paediatric than in adult patients and is similar to the presentation of mumps. It may be unilateral or bilateral and results in xerostomia and pain. Reduced salivary flow may lead to pseudomembranous candidiasis and dental caries. There have been mixed results with the use of antibiotics and glucocorticosteroids in treating this condition. Artificial saliva substitutes or oral lubricants can alleviate the xerostomia.

Hairy leukoplakia

This is uncommon in children, with only a few reported child cases. It occurs predominantly on the lateral border of the tongue and occasionally on the buccal mucosa and the soft palate.

HIV-related periodontitis

HIV-related periodontitis presents with deep pain and spontaneous bleeding, inter-proximal necrosis and cratering, and intense erythema more severe than acute necrotizing ulcerative gingivitis (ANUG). HIV periodontitis appears more frequently in HIV-infected patients who have reduced T4/T8 ratios and symptomatic opportunistic infection. Organisms such as black-pigmented bacteroides and Gram-positive bacilli, which are similar to those found in adult periodontitis, have been identified in HIV periodontitis.

Kaposi’s sarcoma

Uncommon in children and adolescents. The lesion mainly affects the palate, and also the gingivae and the tongue. Treatment is by chemotherapy, radiotherapy or laser excision.

Outcomes

Primary colonization by commensal organisms rather than reactivation of opportunistic infections usually occurs (cytomegalovirus, retinitis and toxoplasmosis are rare). Bacterial infections are also rare, although Streptococcus pneumoniae and Haemophilus influenzae are common respiratory complications. Kaposi’s sarcoma is seen infrequently but lymphomas (especially with central nervous system (CNS) involvement) can occur. The progression of disease process can vary and in many instances, oral and physical symptoms do not often present for years after infection with the immunodeficiency virus. Lymphocytic interstitial pneumonitis is frequently the cause of death for children with AIDS, but is often asymptomatic. There have been major advances in the management of HIV/AIDS with antiretroviral medications and consequently, many children may lead a normal and effective life.

Oncology

Childhood cancer accounts for about 1% of all cancer cases in the population. In Australia, the annual incidence of malignant tumours in children under 15 years is approximately 11 per 100 000 children. Approximately 600–700 children between birth and 15 years of age develop cancer each year. Whereas most adult cancers are carcinomas with strong aetiological associations, childhood cancers are a wide range of different histological types of tumour with less aetiological connection.

The incidence, either in childhood cancer as a whole or in individual types of cancer, varies little from one country to the next and no racial group is exempt. Among more than 50 types of childhood cancers, the most common forms include leukaemias, lymphomas, CNS tumours, primary sarcomas of bone (Figure 12.7A) and soft tissues, Ewing sarcoma, Wilms’ tumours, neuroblastomas and retinoblastomas. Acute leukaemias and tumours of the CNS account for approximately one-half of all childhood malignancies. Multimodal therapy (chemotherapy, radiotherapy and surgery) has resulted in an overall 5-year survival rate for childhood cancer of approximately 70%.

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Figure 12.7 Neoplasms may arise as primary lesions within the jaws, invade from local tumours or may seed as metastases from distant primaries. (A) The panoramic radiograph shows an extensive primary neoplasm of the right mandible involving the infratemporal fossa. Histologically, this lesion was a desmoplastic fibroma and required a hemimandibulectomy. (B) Presentation of a lymphoma in the palate of a 15-year-old girl. The lesion was asymptomatic and the child had merely presented for a routine check-up.

Leukaemia

Leukaemia is a heterogeneous group of haematological malignancies caused by clonal proliferation of primitive white blood cells.

Solid tumours in childhood

Dental management

Close collaboration between the child’s oncologist and the paediatric dentist is essential when planning appropriate dental care. At the time of diagnosis and during the initial stages of chemotherapy, dental care should be provided by the paediatric dentist at the hospital. Once the child has achieved remission, or has successfully completed chemotherapy, routine dental care can often be provided by the child’s own dentist.

Where dental treatment is needed prior to or during chemotherapy, planning with the oncology team is essential. If extractions are required, a FBC including differential white cells and platelets is necessary. If the platelet count is <30 × 109/L, then platelet infusion is indicated and antifibrinolytic agents (doses similar to management of haemostatic disorders) may be helpful. As with immunocompromised children, if the neutrophil count is <1.8 × 109/L, specific antimicrobial prophylaxis should be administered. As many children have been receiving systemic corticosteroids, the possibility of adrenocortical suppression should be considered and additional steroid cover provided as appropriate.

Elective dental treatment should be delayed until the child is in remission or on maintenance chemotherapy. Children in full remission can be treated as normal for most routine dental treatment, although an FBC is prudent if an invasive procedure is planned. Pulpal therapy of primary teeth during the induction and consolidation phase of chemotherapy is contraindicated. When pulpal therapy of permanent teeth is needed, the risk of bacteraemia and potential septicaemia must be weighed against the potential benefits.

Oral hygiene and prevention

It is important to maintain meticulous oral hygiene by using a soft toothbrush during chemotherapy. Four times daily 0.2% chlorhexidine gluconate mouthwashes or gel application to the mucosa helps reduce the symptoms of mucositis and topical and systemic antifungal agents (nystatin or fluconazole) help prevent candidiasis during immunosuppression. Topical lidocaine hydrochloride (Xylocaine Viscous 2%) is helpful during acute episodes of mucositis prior to eating (if possible) or drinking. Prophylactic parenteral antibiotics and antiviral medications, if indicated, are always given during febrile episodes and periods of severe neutropenia to prevent further medical complications.

Immediate oro-dental effects of childhood neoplasia and treatment

Dramatic advances in the treatment of childhood cancer in the past three decades have led to the long-term cure of 70% of the children diagnosed today. Since about 1 in 600 children develop cancer before the age of 15 years, almost 1 young adult in every 1000 will be a long-term survivor of childhood cancer.

As the number of survivors of a variety of paediatric cancers increases, the oro-dental sequelae of effective medical treatment in these patients are emerging. These effects are unique because of the impairment of active growth and development during the cancer therapy. Other late effects include short stature, growth hormone deficiency, cognitive defects, secondary malignancy. Adverse sequelae caused by the cancer treatment can be grouped into postsurgical, post-radiotherapy, post-chemotherapy and combined effects.

Post-radiotherapy (Figure 12.8B)

Radiotherapy produces an initial mucosal inflammation that is often followed by surface sloughing and ulceration (mucositis). The extent of inflammation depends on the location and dosage of radiotherapy and whether fractionated versus whole-dose radiation is used. The most common symptoms following cranial irradiation are oral pain and difficulty in eating and drinking, which are most severe 10–14 days following commencement of radiotherapy. The mucositis usually resolves in another 2–3 weeks after radiotherapy.

When radiotherapy involves the major salivary glands, xerostomia frequently occurs within a few days producing a viscous, acidic saliva. Loss or alteration of taste (hypo- or dysgeusia) may also occur prompting the patient to change to a softer, more cariogenic diet to alleviate soreness and dryness of the oral cavity. This is probably the major factor in the aetiology of rapid dental caries that has been reported in these patients if they are not given adequate preventive therapy. Radiation-induced dental caries has a distinctive generalized cervical pattern and sometimes the complete dentition can be destroyed in a relatively short period.

Progressive endarteritis is a complication that can occur in irradiated bone and can lead to osteoradionecrosis. The mandible is particularly prone to this complication and if such an area of dead bone should become infected following dental extraction, a refractory osteomyelitis may ensue. Endarteritis may also cause fibrosis in the masticatory muscles and subsequent trismus.

Chemotherapy

The cytotoxic drugs used during chemotherapy can cause damage to several organs:

• Liver.

• Kidney.

• Intestine.

• Germ cells of the testes and ovaries.

• Lung.

• Heart.

• Brain.

Direct stomatotoxicity is caused by the cytotoxic action of the chemotherapeutic agents on oral mucosal cells leading to inflammation, thinning and ulceration of the mucosa (mucositis). Saliva function may also be diminished although this response has not been reported as common in children. These problems are commonly encountered in the induction and consolidation phases of chemotherapy when relative high doses of multi-agent therapy are employed. Recent case reports suggest that the incidence and severity of stomatotoxicity is reduced with the concomitant administration of granulocyte colony-stimulating factor (G-CSF) during chemotherapy.

The effects of chemotherapy and radiotherapy appear to be synergistic. Since craniofacial and dental development have not been completed until the adolescent period, it is not surprising that dental late effects are commonly found in survivors of childhood cancer. Chronic problems involving target tissues lead to impairment of growth and development of hard and soft tissues, which may result in orofacial asymmetry, xerostomia, dental caries, trismus and a variety of dental abnormalities. Generally, the nature and degree of these complications vary widely and depend on several factors including the type and location of malignancy, the age of the patient, total dosage and timing of chemotherapeutic agents, and the initial oral health status and the level of dental care before, during and after therapy.

Late oro-dental effects of childhood neoplasia and treatment (Figure 12.9)

The majority of those children for whom oncology treatment results in a stable remission can expect to follow a healthy life. Recurrence of the original malignancy may occur although the likelihood of this becomes increasingly remote as time passes. Consequently, successfully treated paediatric oncology patients are never ‘discharged’, their health being regularly monitored throughout their life.

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Figure 12.9 Effects of radiation to the head and neck. A set of identical twins, the first of which (A) had acute lymphoblastic leukaemia diagnosed at 18 months. She relapsed during the first remission and received a bone marrow transplant and total body irradiation (TBI). The comparison with her sister (B) at 15 years of age is dramatic. There is agenesis of some permanent teeth, arrested root development of the incisors and first permanent molars, and microdontia.

With the exception of those children treated with radiotherapy to the orofacial region, the majority of children are no more prone to dental and periodontal disease than the well child, and often exhibit excellent oral health. However, long-term oro-dental effects of radiotherapy can influence dental management.

Growth disturbances

Following head and neck radiotherapy, facial growth can be impaired and alterations to developing teeth can occur. Children younger than 5 years of age are affected more severely than older patients. An altered craniofacial growth pattern with diminished mandibular growth, is often associated with a field of irradiation that includes a portion of ascending ramus and the entire condyle of the mandible. Dental effects may include:

• Incomplete calcification.

• Enamel hypoplasia.

• Arrested or altered root development, and premature closure of the root apices can complicate permanent tooth development.

• Microdontia and agenesis of teeth are also common (Figure 12.9A).

The exact nature and extent of damage depends on the stage of dental development and the timing and dosage of irradiation. The lack of specificity of cytotoxic agents in terms of differentiating neoplastic cells from metabolically active normal cells, such as ameloblasts and odontoblasts, can result in abnormalities of dental development. Microdontia, enlarged pulp chambers, shortening, thinning and blunting of the root apex and delayed tooth eruption have been frequently reported in children receiving chemotherapy. Enamel opacities, hypocalcification and a high rate of dental caries have also been reported in several studies, however, it remains unclear whether these findings are due to direct alteration of enamel formation or maturation or to alterations in the oral environment (saliva and flora), diet and home care often observed among young patients on chemotherapy.

Xerostomia

Cranial irradiation can also irreversibly damage the acini cells of the major salivary glands and xerostomia can occur in children. This condition is often transient due to the lower dosage of radiation used and greater regenerative capacity of the exocrine cells in children. Generally, there is a lower incidence of radiation-induced dental caries in children compared with adults. Regular nightly fluoride mouth rinsing is required to prevent enamel demineralization during this critical period.

Other less common effects

Epidermal and mucosal changes include skin hyperpigmentation, cutaneous telangiectasia, subcutaneous tissue atrophy and permanent thinning or loss of hair. Disturbances of intellectual, endocrine and germ cell development have also been reported following cranial irradiation. However, the mean age of dental maturation in children following cranial irradiation is within the normal range.

Since most craniofacial tumours are treated by combined chemotherapy and head and neck irradiation, it is difficult to know the exact effect of each treatment. In general, late oro-dental effects are more severe in patients who receive a higher-dosage treatment either with chemotherapy or radiotherapy. Dental aberrations are more severe and extensive in patients younger than 6 years of age due to the immature development of the permanent teeth. Total body irradiation in bone marrow transplantation appears to increase the risk of disturbance to dental development.

Complications associated with bone marrow transplantation

Almost all children undergoing bone marrow transplantation develop the typical oral mucosal changes of ulceration, keratinization and erythema that develops in 4–14 days post-transplantation. Mucosal atrophy is also frequently associated with ulceration between 1 and 3 weeks after bone marrow transplantation. During this period, oral pain is often severe with many patients requiring narcotic analgesia. The use of keratinocyte growth factor (palifermin) has been demonstrated to reduce this complication in adults undergoing autologous transplantation and paediatric studies of this promising treatment are in progress.

As mentioned previously, oral infection with Candida albicans, herpes simplex, cytomegalovirus and varicella zoster are the major infective agents seen in children undergoing bone marrow transplantation, if inadequate prophylaxis is given. These conditions can be life-threatening if not treated aggressively at diagnosis.

Oral manifestations of defective haemostasis are common but seldom serious and include mucosal bleeding or crusting of the lips and gingival oozing.

Graft-versus-host disease (GVHD)

This condition occurs when transplanted T cells recognize the host tissues as foreign. GVHD is a major problem following bone marrow transplantation with clinical manifestations in up to half of patients. The acute form of GVHD tends to occur within weeks of bone marrow transplantation, with signs of fever, rash, diarrhoea and abnormal liver function leading to jaundice. Chronic GVHD may follow some months later and is characterized by lichenoid or scleroderma-like changes of the skin, keratogingivitis, abnormal liver function, pulmonary insufficiency and intestinal problems. Oral manifestations of GVHD vary with the severity of the conditions but often include:

• Mild oral mucosal erythema.

• Painful desquamative gingivitis.

• Angular cheilitis.

• Loss of lingual papillae.

• Lichenoid patches of the buccal mucosa.

• Striae on the buccal mucosa with subsequent restriction of mouth opening.

• Xerostomia.

• Mucosal atrophy, erosion and ulcerations.

Management of chronic GVHD necessitates a multidisciplinary approach. The goal of treatment entails effective care as well as minimizing toxicity and relapse. Long-term systemic immunosuppression with prednisone and other agents is often needed. Recently, extracorporeal photopheresis has been known to produce disease remission. Topical treatments can be effective such as dexamethasone mouthwashes, Biotene moisturizing drops, Difflam-C, and sodium bicarbonate diluted in water helps with disturbances in taste (dysgeusia). Careful attention to oral health with close communication with the treating medical team is needed to give the best outcomes.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Osteonecrosis of the jaw is a well-described complication of bisphosphonate therapy in adults and has not yet manifested as a disorder in children. While there have been no reported cases of bisphosphonate-related osteonecrosis (BRONJ) in children, there has been a significant increase in the use of these drugs in the management of children with connective tissue disorders and decreased bone density including:

• Congenital osteoporosis – osteogenesis imperfecta.

• Secondary osteoporosis – immobility, steroid induced.

• Focal orthopaedic conditions – avascular necrosis (AVN), Perthes’ disease; fracture non-union; Ilizarov limb lengthening; bone cysts.

• Other bone disorders – fibrous dysplasia, idiopathic juvenile osteoporosis.

There is an increased association of BRONJ with any invasive dental procedure such as extractions. While the risks for children are unknown, clinicians should be aware of this potentially destructive condition. There is no concurrence regarding the optimal bisphosphonate drug in children, dosage or duration of treatment. The more serious side-effects linked to bisphosphonates in adults such as uveitis, thrombocytopenia or oesophageal or oral ulcerations are rare in children. Potent bisphosphonates have established therapeutic half-lives of over 30 years, so there may be long term, a low to very low, residual risk of BRONJ in these patients.

Adolescents and young adults requiring bisphosphonate therapy, particularly in the setting of malignancy may also be at increased risk of BRONJ and caution needs to be applied in the undertaking of extractions and oral surgery in this select patient group.

Nephrology

Renal disorders

Renal diseases are classified as acute, chronic, acquired or congenital conditions.

Renal osteodystrophy (Figure 12.9A)

Lytic lesions of the mandible or maxilla, known as Brown’s tumours, can also occur in severe renal failure due to secondary hyperparathyroidism. Histologically, these lesions are similar to giant cell tumours and usually resolve following correction of hypocalcaemia and hyperphosphataemia with vitamin D metabolites. Hypocalcaemia occurs due to increased phosphate retention and decreased calcium absorption. Active calcium absorption from the gut depends on the presence of the active metabolite, 25-hydroxy-cholecalciferol (vitamin D3). However, vitamin D metabolism is impaired due to failure of the hydroxylation of 25-hydroxy-cholecalciferol to 1,25-dihydroxy-cholecalciferol in the diseased kidney. In an attempt to raise serum calcium there is a secondary hyperparathyroidism and calcium is removed from bone stores giving rise to the characteristic radiographic appearance of renal osteodystrophy. Other dental manifestations include demineralization, decreased trabeculation, loss of lamina dura, macrognathia, tooth mobility, malocclusion, enamel hypoplasia and pulp stones.

Renal transplantation

A pre-transplant dental assessment is essential to reduce the risk of oral complications following organ transplant and immunosuppression. The presence of dental caries and oral infections will necessitate delay in transplantation until all potential foci of infection are eliminated. Comprehensive dental treatment and institution of a rigorous preventive programme are recommended prior to transplant to reduce the risk of subsequent oral diseases. Antibiotic prophylaxis as per the protocol for prevention of infective endocarditis is essential prior to invasive surgical procedures.

Gastroenterology

Inflammatory bowel disease (see Chapter 8)

Commonly, ‘chronic inflammatory bowel disease’ entails ulcerative colitis and Crohn disease that may represent ends of a spectrum of tissue reaction to a common agent. Establishing an aetiological agent is difficult. Both conditions present as a chronic inflammatory process of the gastrointestinal tract with acute exacerbations. Of particular interest to the dentist, is the association with orofacial granulomatosis that sometimes precedes the onset of ulcerative colitis by 1–2 years.

Oral changes reported in some children include linear ulceration or fissuring of the buccal and labial mucosa, diffuse swelling of the lips, angular cheilitis and diffusely swollen erythematous gingivae, chronic granulomatous lesions. These lesions may improve with sulfasalazine (Salazopyrin) therapy but usually reappear on the buccal mucosa periodically.

Endocrinology

Diabetes mellitus

Type 1 or insulin-dependent diabetes mellitus (TIDM) is the most common form of diabetes in children. Approximately 1 in 1200 children between the ages of 5 and 18 years have the disease. Type 1 diabetes results from autoimmune destruction of the insulin-producing β cells in the pancreas, which is thought to be triggered by viral or toxic insults to the pancreas in the child genetically predisposed to developing the disorder. The goal of treatment is to maintain blood glucose levels in a range that prevents the development of short-term and long-term complications. The target blood glucose ranges are 5–12 mmol/L in children less than 5 years of age, 4–10 mmol/L for middle childhood and 4–8 mmol/L thereafter.

Dental management

• Children with well-controlled diabetes can receive dental treatment in the usual way, except when a general anaesthetic is required. The best measure of control is the level of glycosylated haemoglobin (HbA1c). The target for most children is a value of <6.5–7.0% (≤53 mmol/mol). For routine dental appointments, the child should eat a normal meal prior to the dental procedure although a glucose source should always be available to treat hypoglycaemia.

• Fasting before a general anaesthetic requires careful blood glucose monitoring and adjustment of insulin doses during the fasting period. This is to prevent extremes of hyper- and hypoglycaemia. Insulin doses and the possibility of intravenous fluid therapy should be discussed with the child’s treating paediatrician/endocrinologist.

• Post-surgical healing can be delayed, particularly if blood glucose control is suboptimal and oral sepsis can be an additional risk.

• It is often possible to manage many T1DM children requiring general anaesthesia in day-stay facilities, provided that children can begin taking fluids shortly after their procedure. Other children may require admission to a paediatric hospital, with a dextrose and insulin infusion set-up to maintain BGL levels and avoid complications during the fasting and postoperative periods. It is obviously essential to liaise with the treating endocrinologist.

• Prophylactic antibiotic therapy is recommended prior to surgical procedures.

Pituitary disorders

Hypopituitarism

Hypopituitarism (complete or partial) may be either congenital or secondary to pituitary or hypothalamic disease (tumours, infections, trauma or after exposure to ionizing radiation). These children need to be managed in conjunction with a paediatric endocrinologist to prevent potentially serious complications of pituitary hormone deficiency.

Isolated growth hormone (GH) deficiency is the most common pituitary hormone deficiency, but evolution of other deficiencies may take place over time. Treatment consists of supplemental GH that stimulates the differentiation of epiphyseal growth plate precursor cells and induces clonal expansion of cartilage cells. Timely detection and treatment of GH deficiency is essential to minimize the growth disturbance.

Thyroid disorders

Hypothyroidism

Thyroid hormone deficiency (hypothyroidism) is most often due to a primary disorder of the thyroid gland and less commonly secondary to hypothalamic and/or pituitary insufficiency. Primary hypothyroidism may be either congenital or acquired (thyroiditis, after radiation exposure or surgical excision). Untreated congenital hypothyroidism leading to severe developmental delay (Cretinism) is rare in those countries where neonatal testing is performed (TSH with or without fT4) and treatment with synthetic thyroxine started in the first 1–2 weeks of life. Congenital hypothyroidism can be attributed to aplasia, hypoplasia or maldescent of the thyroid gland, abnormal thyroid hormone production (dyshormonogenesis) or prenatal iodide deficiency. Juvenile hypothyroidism can stem from autoimmune thyroiditis, thyroidectomy, thyroid irradiation, infection or medication.

Although hypothyroid changes can include: growth failure, diminished physical activity, decreased circulation, poor muscle tone, speech disorders, delayed mental development and craniofacial manifestations, these changes are obviously dependent on the age of onset of the disease, the degree of hypothyroidism and the timing of diagnosis and treatment. Most hypothyroid children have very few clinical features, despite a quite severe deficiency state.

Parathyroid disorders

Hyperparathyroidism

Excessive production of parathyroid hormone may result from a primary defect in the gland (adenoma, hyperplasia, hypertrophy) or secondarily as a compensatory phenomenon, usually correcting hypocalcaemic states due to rickets or from chronic renal disease. Tertiary hyperparathyroidism (autonomous hyperparathyroidism) can occur following prolonged and uncontrolled secondary hyperparathyroidism. Primary and tertiary disease results in hypercalcaemia and hypercalcuria, muscle weakness, abdominal pain and constipation, polyuria, polydipsia, kidney stones and bone loss. In infants and young children, there may be failure to thrive, poor feeding and muscular hypotonia.

The bony lesions are rarely seen in children but include brown tumours, so-called because they contain areas of haemorrhage, an abundance of multinucleated giant cells, fibroblasts and haemosiderin. Hypophosphataemia can lead to rickets in children and osteomalacia in adults. Generalized osteoporosis with cortical resorption is the most common bone lesion in adults and radiographic signs can also include multiple rarefactions, loss of typical trabeculation, ground-glass appearance and metastatic calcifications.

Adrenal gland disorders

Adrenal glands have two endocrine functions, located within the cortical and medullary areas. The adrenal cortex produces three major classes of steroid hormones: glucocorticoids, mineralocorticoids, and sex hormones. Glucocorticoids (cortisol) have an important role in carbohydrate, fat and protein metabolism, assist in the maintenance of normal blood pressure and protect the body against stresses of various types. Mineralocorticoids (aldosterone) help maintain salt and water balance through their action on the kidney. Adrenal sex hormones help complement the actions of the gonadal steroids in the development of sexual characteristics and reproductive capability.

Neurology

Febrile convulsion

This is a term used to describe a child under 5 years of age who has a seizure in response to a febrile illness. It usually occurs with body temperatures over 38°C and when no other cause can be determined. Recurrent, non-febrile seizures are termed as epilepsy.

Dental management

Management of gingival hypertrophy (Figure 12.9B) is dependent on oral hygiene and dental development at diagnosis. In the permanent dentition, full mouth gingivectomy may be required, but gingival overgrowth will recur if oral hygiene is not optimal. Maintenance of adequate oral hygiene may be especially difficult in children with additional intellectual disability and is highly dependent on the motivation and skill of the parents and caregivers. Battery-operated plaque removers with small circular heads are beneficial in the maintenance of good oral hygiene in the more intractable cases. The use of daily chlorhexidine-containing gels is effective in reducing the inflammatory component of the gingival overgrowth. It is important to always keep the interests of the child in mind, particularly with regard to aggressive surgical treatment that may not benefit the child in the long term.

The general goal of dental management is the avoidance of a seizure. It is important to know the type of epilepsy and any precipitating factors, medications and dosage, compliance and degree of seizure control before commencing treatment. In addition, drug interactions with anticonvulsants are common and their half-life and blood levels can be increased substantially. Consultation with the child’s neurologist is essential before commencement of treatment.

The following management protocol is recommended for prevention and control of seizures in the dental surgery:

• Reduce stress to the child by behavioural management and conscious sedation techniques.

• Reduce direct overhead lighting, particularly for the photosensitive form of epilepsy.

• Avoid seizure-promoting medications, such as CNS stimulants and local anaesthetics containing adrenaline (epinephrine).

• Emergency drugs such as oxygen, intravenous or rectal diazepam (Valium) and intravenous phenobarbital sodium should be readily available.

• Pre-arranged transfer to a paediatric hospital, in case required.

General anaesthesia is preferable in children with poor seizure control as the abnormal neural activity is completely ablated during the procedure. Dental trauma is an obvious consequence in the child with frequent, poorly controlled seizures. Removable appliances are contraindicated in an epileptic child due to potential airway obstruction.

Respiratory disease

Asthma

Australia has one of the highest rates of childhood asthma in the world, with 1 in 5 children and 1 in 7 adolescents affected. It is a respiratory condition characterized by increased responsiveness of the airways to a wide variety of stimuli, leading to widespread narrowing of the airways resulting in symptoms of dyspnoea, wheezing and coughing. Precipitating factors include emotional stress, exercise, cold air, viral respiratory infections, air pollution and aspirin. The condition is reversible, either spontaneously or as a result of bronchodilator therapy. Currently, there is an emphasis on prophylactic medications to prevent episodes rather than simply treating acute attacks.

Bronchodilators include β2-adrenergic drugs such as salbutamol sulphate (Ventolin) and theophylline (Nuelin). Preventive agents include disodium cromoglycate (Intal) and oral corticosteroids such as prednisone and inhaled corticosteroids such as beclomethasone dipropionate (Beclovent) and salmeterol xinafoate (Seretide).

Genetics and dysmorphology

Diagnosis

Although individually uncommon, many children with genetic disorders will present to the paediatric dentist with specific dental anomalies associated with their condition or medical problems that complicate their dental management. Never assume that all conditions will have been diagnosed before they present, as many children are often diagnosed as having a significant genetic disorder quite late in childhood, either because the condition has late manifestations or because features have simply been missed. When taking a history, it is always useful to draw a simple three-generation family pedigree (Figure 12.13).

image

Figure 12.13 Calculation of risk in an X-linked recessive disorder. For a carrier mother (illustrated), there is a 50% chance that sons will be affected and a 50% chance that daughters will be carriers; for an affected father, no sons will be affected but all daughters will be carriers.

Many disorders do not follow Mendelian inheritance patterns, but are clearly of ‘familial’ or hereditary nature. Many important and common conditions fall into this group; they are often not single entities but causally heterogeneous and are seen as the end result of multiple gene effects against a variable environmental background (multifactorial or polygenic), e.g. cleft lip and palate.

One in 170 live-born births has a major chromosomal abnormality. Chromosomal abnormalities, particularly those involving imbalance of the autosomes, usually result in developmental delay and dysmorphic features and often include multi-system anomalies. These include numerical abnormalities (trisomy 21 or Down syndrome) and structural abnormalities such as segmental deletions (cri-du-chat syndrome), duplications and unbalanced translocations. Numerical abnormalities of the sex chromosomes are better tolerated than those of the autosomes and include conditions such as Turner syndrome (45, X) in females and Klinefelter syndrome (47, XXY) in males. Standard cytogenetic karyotyping is now being replaced by DNA-based chromosome micro-arrays (CMA) that can detect many more significant submicroscopic deletions and duplications (pathological copy number variations). Many other genetic disorders are caused by mutations within genes, which cannot be detected by karyotype or CMA analysis, but may be able to be confirmed by targeted gene testing after a syndrome is recognized (Table 12.1).

The first step in making a diagnosis is the recognition that the child is dysmorphic or unusual looking. It is the pattern of dysmorphism and associated malformations rather than a single feature that aids diagnosis. Accurate diagnosis is the key to prognosis, management and sometimes the underlying genetic cause of the disorder. It also helps the parents, as it removes the anxiety of uncertain aetiology and prognosis.

The diagnostic procedure involves history, clinical examination and laboratory investigations. Based on the above information, children can be divided into three basic groups:

• Fetal environmental syndromes (teratogens, compression).

• Developmental anomalies.

• Genetic syndromes.

Referral to a genetic clinic is recommended for all children with multiple anomalies or dysmorphic features of unknown cause. Syndrome diagnosis aids (available by paid subscription) such as POSSUM (www.possum.net.au) or the London Dysmorphology Databases (www.lmdatabases.com/) can assist. Laboratory investigations include radiographic survey, chromosomal or microarray analysis, biochemical screening of urine or blood or cultured fibroblasts for specific enzymatic or protein deficiencies if a metabolic disorder is suspected. Referral to a genetics clinic is usually recommended to further elaborate a diagnosis and to assist with specialized genetic testing and genetic counselling.

It is not the intention of this section to detail those anomalies with a major craniofacial or orofacial manifestation, of which dental clinicians should be aware. The reader is directed to texts and online sources that more comprehensively cover these conditions (see References and further reading, below).

Terms used in morphogenesis

Sequence

A pattern of multiple anomalies arising from a single structural defect or event; previously termed anomalad. They usually originate early in development with single problems that create secondary anomalies and manifest with multiple defects at birth or later. These sequences may be divided into three basic groups:

Risk of recurrence in genetic disorders

X-linked (sex-linked)

• 50% risk of transmission from female carriers to sons (who would then be affected) or daughters (who would then be a carrier).

• No male-to-male transmission from affected fathers to sons, but all daughters will be carriers.

The terms ‘X-linked recessive’ and ‘X-linked dominant’ are used to describe sex-linked conditions with an altered frequency of phenotypic expression. Males usually have only one X chromosome; males with an X-linked abnormality are described as hemizygous for the trait, and will be affected. Females usually have two X-chromosomes; female carriers of an X-linked trait are heterozygous. In X-linked recessive disorders, female carriers can be unaffected or affected (manifesting carrier) but the latter are usually much less severely affected than males. Rarely, females are homozygous for an X-linked trait, so will be affected as severely as a hemizygous male. ‘X-linked dominant’ traits manifest in females and males, but males are often more severely affected.

The degree of phenotypic expression in heterozygous females is determined by the pattern of X inactivation (Lyonization, see Chapter 11) in each tissue. For example, some female carriers of haemophilia A will show a measurable (but subclinical) reduction in factor VIII; and those that carry X-linked hypohidrotic ectodermal dysplasia may also show some phenotypic variation in the dentition such as microdontia and oligodontia, but not to the same extent as in hemizygous males. The markedly increased frequency of females seen with some ‘X-linked dominant’ conditions, such as incontinentia pigmenti or focal dermal hypoplasia (Goltz–Gorlin syndrome) is explained by male lethality for these mutations in most hemizygous males.

Prenatal tests for genetic disorders

Ultrasound

Ultrasound has become a routine investigation for most pregnancies. It is non-invasive to the mother and the fetus and there are many anomalies that may be diagnosed by this technique. Common ultrasound techniques include the first trimester nuchal translucency measurement (a screening examination for Down syndrome risk) and the mid-trimester fetal morphology scan.

Amniocentesis

This is the sampling of cells from amniotic fluid at around 15–18 weeks. A number of tests can be performed including:

• Karyotyping.

• Sex determination.

• DNA diagnosis.

• Enzyme assays.

Chorionic villus sampling

This test is performed earlier than amniocentesis, at around 11–13 weeks. Similar tests are performed to those done with amniocentesis, although it has the advantage of earlier diagnosis.

Preimplantation genetic diagnosis (PGD)

This is DNA testing of cells biopsied from IVF embryos. This is an option increasingly chosen by couples where genetic risk is high, abortion is not an acceptable option and targeted testing is possible (prior work-up is required).

Further reading

Endocarditis

See Appendix E.

Haematology

1. Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surgery, Oral Medicine, and Oral Pathology. 1988;66:297–303.

2. Morimoto Y, Yoshioka A, Sugimoto M, et al. Haemostatic management of intraoral bleeding in patients with von Willebrand disease. Oral Diseases. 2005;11:243–248.

3. Piot B, Sigaud-Fiks M, Huet P, et al. Management of dental extractions in patients with bleeding disorders. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002;93:247–250.

4. Warrier AI, Lusher JM. DDAVP: a useful alternative to blood components in moderate hemophilia A and von Willebrand’s disease. Journal of Paediatrics. 1983;102:228.

Immunodeficiency

1. Flaitz CM, Hicks MJ. Oral candidiasis in children with immune suppression: clinical appearance and therapeutic considerations. ASDC Journal of Dentistry for Children. 1999;66:161–166.

2. Malech HL, Nauseef WM. Primary inherited defects in neutrophil function: etiology and treatment. Seminars in Hematology. 1997;34:279–290.

3. Moyer IN, Kobayashi RH, Cannon ML. Dental treatment of children with severe combine immunodeficiency. Pediatric Dentistry. 1983;5:79.

4. Porter SR, Scully C. Orofacial manifestations in the primary immunodeficiency disorders. Oral Surgery, Oral Medicine, and Oral Pathology. 1994;78:4–13.

5. Woroniecka M, Ballow M. Office evaluation of children with recurrent infection. Pediatric Clinics of North America. 2000;47:1211–1224.

Acquired immunodeficiency syndrome

1. Eldridge K, Gallagher JE. Dental caries prevalence and dental health behaviour in HIV infected children. International Journal of Paediatric Dentistry. 2000;10:19–26.

2. Frezzini C, Leao JC, Porter S. Current trends of HIV disease of the mouth. Journal of Oral Pathology and Medicine. 2005;34:513–531.

3. Hicks MJ, Flaitz CM, Carter AB. Dental caries in HIV-infected children: a longitudinal study. Pediatric Dentistry. 2000;22:359–364.

4. Ramos-Gomez FJ, Flaitz C, Catapano P. Classification, diagnostic criteria, and treatment recommendations for orofacial manifestations in HIV-infected pediatric patients Collaborative Workgroup on Oral Manifestations of Pediatric HIV Infection. Journal of Clinical Pediatric Dentistry. 1999;23:85–96.

Oncology

1. American Academy of Pediatric Dentistry Clinical Affairs Committee. American Academy of Pediatric Dentistry Council on Clinical Affairs 2005–2006 Guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation, and/or radiation. Pediatric Dentistry Reference Manual Volume. 2008;34(6):280–286.

2. da Fonseca MA. Dental care of the pediatric cancer patient. Pediatric Dentistry. 2004;26:53–57.

3. Dahllöf G, Barr M, Bolme P, et al. Disturbances in dental development after total body irradiation in bone marrow transplant recipients. Oral Surgery, Oral Medicine, and Oral Pathology. 1988;65:41–44.

4. Dignan FL, Scarisbrick JJ, Cornish J, et al. Organ-specific management and supportive care in chronic graft-versus-host disease. British Journal of Haematology. 2012;158:62–78.

5. Ferretti GA. Chlorhexidine prophylaxis for chemotherapy and radiotherapy induced stomatitis: a randomized double-blind trial. Oral Surgery, Oral Medicine, and Oral Pathology. 1990;69:331–338.

6. Reid H, Zietz H, Jaffe N. Late effects of cancer treatment in children. Pediatric Dentistry. 1995;17:273–284.

Bisphosphonate-associated osteonecrosis

1. Bachrach LK, Ward LM. Clinical review 1: Bisphosphonate use in childhood osteoporosis. Journal of Clinical Endocrinology and Metabolism. 2009;94:400–409.

2. Brown JJ, Ramalingam L, Zacharin MR. Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children? Clinical Endocrinology. 2008;68:863–867.

3. Malmgren B, Astrom E, Soderhall S. No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates. Journal of Oral Pathology and Medicine. 2008;37:196–200.

4. Milano M, Wright T, Loechner KJ. Dental implications of osteogenesis imperfecta: treatment with IV bisphosphonate: report of a case. Pediatric Dentistry. 2011;33:342–352.

5. Sambrook P, Olver I, Goss A. Bisphosphonates and osteonecrosis of the jaw. Australian Family Physician. 2006;35:801–803.

6. Schwartz S, Joseph C, Iera D, et al. Bisphosphonates, osteonecrosis, osteogenesis imperfecta and dental extractions: a case series. Journal of the Canadian Dental Association. 2007;74:537–542.

Nephrology

1. Lucas VS, Roberts GJ. Oro-dental health in children with chronic renal failure and after renal transplantation: a clinical review. Pediatric Nephrology. 2005;20:1388–1394.

Gastroenterology

1. Dodds AP, King D. Gastroesophageal reflux and dental erosion: case report. Pediatric Dentistry. 1997;19:409–412.

2. Little JW, Rhodus NL. Dental treatment of the liver transplant patient. Oral Surgery. 1992;73:419–426.

3. Seow WK, Shepherd RW, Thong YH. Oral changes associated with end-stage liver disease and liver transplantation: implications for dental management. Journal of Dentistry for Children. 1991;58:474.

4. Wondimu B, Németh A, Modéer T. Oral health in liver transplant children administered cyclosporin A or tacrolimus. International Journal of Paediatric Dentistry. 2001;11:424–429.

Endocrinology

1. Dahms WT. An update in diabetes mellitus. Pediatric Dentistry. 1991;13:79.

2. Fabue LC, Soriano YJ, Pérez MG. Dental management of patients with endocrine disorders. Journal of Clinical and Experimental Dentistry. 2010;2:e196–e203.

3. Lalla E, Cheng B, Lal S. Diabetes-related parameters and periodontal conditions in children. Journal of Periodontal Research. 2007;42:345–3490.

4. Milenkovic A, Markovic D, Zdravkovic D, et al. Adrenal crisis provoked by dental infection: case report and review of the literature. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics. 2010;110:325–329.

5. Twetman S, Petersson GH, Bratthall D. Caries risk assessment as a predictor of metabolic control in young type 1 diabetics. Diabetic Medicine. 2005;22:312–315.

6. Whitlock RI. The jaw lesions associated with hyperparathyroidism. Transactions of the International Conference on Oral Surgery. 1970;1970:322–329.

7. Wray L. The diabetic patient and dental treatment: An update. British Dental Journal. 2011;211:209–215.

Neurology

1. Nelson LP, Ureles SD, Holmes G. An update in pediatric seizure disorders. Pediatric Dentistry. 1991;13:128–135.

Respiratory disease

1. Stensson M, Wendt LK, Koch G, et al. Oral health in pre-school children with asthma – followed from 3 to 6 years. International Journal of Paediatric Dentistry. 2010;20:165–172.

2. Zhu JF, Hidalgo HA, Holmgreen WC, et al. Dental management of children with asthma. Pediatric Dentistry. 1996;18:363–370.

Genetics and dysmorphology

1. Hennekam RCM, Krantz ID, Allanson JE. Gorlin’s Syndromes of the Head and Neck. Fifth edn New York: OUP; 2010.

2. Jones KL. Smith’s Recognizable Patterns of Human Malformation. Sixth ed Philadelphia: Elsevier Saunders; 2006.

3. Online Mendelian Inheritance in Man. In: www.ncbi.nlm.nih.gov/omim;.