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Early Tooth Loss Due to Cyclic Neutropenia: Long-Term Follow-Up of One Patient

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Early Tooth Loss Due to Cyclic Neutropenia: Long-Term Follow-Up of One Patient .................... ................................................ ARTICLE Marcio A. da Fonseca, DDS, MS, Fernanda Fontes, DDS, MS Early tooth loss due to cyclic neutropenia: long-term follow-up of one patient the first line of defense against infec- In young patients with abnormal entists and dental hygienists tion, their depletion can be fatal, loosening of teeth and periodontal play an important role in the although the child may appear healthy breakdown, dental professionals early detection of diseases or between cycles.6 The diagnosis is made should consider a wide range of etio- D conditions whose initial signs are by documentation of two cycles of logical factors/diseases, analyze dif- seen in the oral cavity. In cases of decreased neutrophil count observed ferential diagnoses, and make appro- abnormal loosening of teeth and in complete blood count (CBC) tests priate referrals. The long-term oral periodontal breakdown without an done twice weekly for 6 weeks.' and dental follow-up of a female apparent cause, the dental profes- This report reviews the oral mani- patient diagnosed in early infancy sional must be prepared to investi- festations of CN and presents the case with cyclic neutropenia is reviewed, gate a wide range of differential diag- of an adult female who has been fol- and recommendationsfor care are noses, recommend further investiga- lowed by our pediatric dental service discussed. tion, and make appropriate referrals. since early infancy. Cyclic neutropenia (CN) is charac- terized by a transient decrease in the neutrophil count, with a periodicity Case report of approximately 21 days (range, 14 Shortly after birth, in February, 1978, to 36 days).',2 It is inherited as an our patient had pustular skin infec- autosomal-dominant condition in tions from which Staphylococcus about one-third of the patients, with uureus was cultured, followed by sev- the remaining cases having an eral episodes of fungal diaper rash unclear mode of inheritance.' CN is and otitis media (OM). A CBC caused by a defect in early obtained at 7 months of age, after she hematopoietic precursor cell develop- presented with abscesses on the but- ment (more pronounced in the tocks, showed a white blood count myeloid precursors), leading to a cell (WBC) of 7000/mm3, with a dif- periodic failure of neutrophil produc- ferential count of 40% neutrophils, tion in the bone rnarrow.lr2 It has also 55% lymphocytes, and 5% monocytes been suggested that granulocyte (for normal blood values, refer to the colony-stimulating factor (G-CSF) Table). Further studies revealed posi- production is affected.l.2 Oscillations tive myeloperoxidase, normal in other hematopoietic elements immunoglobulins, normal S. uweus such as monocytes, reticulocytes, and bactericidal activity, and normal platelets are also seen.l.3 chemotactic migration. Otitis media Manifestations of the disease and skin infections continued to appear in early childhood, even occur intermittently, and by her first though it may develop at any age.415 birthday, she was placed on daily sul- These manifestations include fever, fisoxazole for 3 months, which failed malaise, aphthous stomatitis, skin to resolve her infections. Fever, neu- infections, pharyngitis, and lym- tropenia, facial cellulitis caused by phadenitis.1-3.6 They typically appear mosquito bites, upper respiratory one to three days prior to changes in tract infections, infected thumbs, leg the blood count and may persist from sores, and oral infections led to multi- 3 to 10 days.4 Because neutrophils are ple hospitalizations. The patient had SCD Special Care In Dentistry, Vol20 No 5 2000 18'1 Table. Blood count normal reference values.17 growth factors were prescribed, few oral lesions have been observed, and hospitalizations have decreased to Complete Blood Count Normal Value about twice a year. At age 5, her only remaining teeth Hemoglobin (g/dl) males, 14-18; females, 12-16 were the maxillary right second newborns, 16-19; children, 11-16 molar and the canines. Bone loss was uniform, and the family was coun- Hematocrit (%) males, 40-54; females, 37-47 seled about the poor prognosis for newborns, 49-54; children, 35-49 retaining her permanent dentition. At 6 years of age, the maxillary left per- manent first molar was removed, and White blood cells 5000-10,000 cells/mm3 root caries was noted on both Platelets 150,000-400,000 cells/mm3 mandibular first molars. Despite repeated counseling, oral hygiene was not optimal at most visits, with Differential Blood Count Normal Value the gingival tissues consistently appearing erythematous, edematous, Neutrophils 50-70% and bleeding on contact. In Lymphocytes 30-40% November of 1998, clinical and radi- Monocytes 3-7% ographic examinations revealed poor Eosinophils 0-5% oral hygiene, generalized periodontal breakdown with pocket formation, Basophils 0-1 % gingival recession, moderate to severe mobility of all teeth, severe Absolute Neutrophil Count (ANC) = WBC x (%segs + % bands) bone loss, and caries (Figs. 1-3). Complete exodontia was performed uneventfully while the patient was difficulties with feeding, toothbrush- ferential count of 38% monocytes, under intravenous sedation with ing, and taking oral medications 22% eosinophils, 37% lymphocytes, midazolam hydrochloride and because of painful mouth ulcers. 1% segmented neutrophils, and 1% ketorolac tromethamine. Before the Gingival bleeding, severe gingivitis, bands. The majority of the neu- procedure, her blood values were significant bone loss, and loose pri- trophils showed a lack of maturation. WBC = 9900/mm3, hemoglobin = mary teeth were evident by 2 years of After additional blood tests, the 11.4 g/dl, hematocrit = 33.8%, age. Because of the oral problems, the patient was diagnosed with severe platelets = ZOO,OOO/mm3, and ANC = examining pediatric dentist asked for congenital CN. She was initially treat- 2.2. She was prescribed clindamycin the CBC to be repeated, and it ed with steroids, followed by daily for 10 days, 0.12% chlorhexidine rins- revealed abnormalities: hemoglobin = subcutaneous injections of G-CSF and es twice daily for a week, and ketoro- 8.9 g/dl, platelets = 705,00O/mm3, GM-CSF (granulocyte macrophage lac tromethamine for 5 days. After and WBC = 11,80O/mm3, with a dif- colony-stimulating factor). After the adequate tissue healing, complete Fig 1. Gingival recession, erythematous and edematous tlssues, plaque accumulation. Fig 2. Perlodontal breakdown. 168 SCD Special Care In Dentistry, Vol20 No 5 2000 dentures were made for her. relieve the oral Interestingly, following the extrac- pain. Because tions, her blood counts improved to a these are contact level not previously seen by her medications, the hematoIogist. patients should rinse or bathe the Discussion oral tissues for at In hematologic disorders such as CN, least 3 minutes; prolonged neutropenia and neu- otherwise the trophil dysfunction can lead to life- desired effect will threatening infections.7 Therefore, not be produced. prompt treatment of infections with Diluting the vis- antibiotics and administration of cous lidocaine a hematopoietic growth factors, such as little with water G-CSF and GM-CSF, are required.1.2 makes rinsing Growth factors are glycoproteins that easier. These stimulate the proliferation of bone anesthetic solu- marrow stem cells and their subse- tions can also be Fig 3. Panoramic radlograph showing extensive bone loss, caries, quent maturation into fully differenti- applied directly to and several missing (extracted) permanent teeth. ated peripheral blood elements.*G- the ulcers with-a cot- CSF, the critical cytokine for mainte- ton tip if the patient nance of a normal neutrophil count,lO is not able to rinse and spit. Gargling nisms that protect against oral infec- also potentiates the functional prop- and swallowing are not advised, tions leads to bone loss with occlusal erties of mature cells by increasing since loss of gag reflex can result in dysfunction and premature loss of phagocytic activity, antimicrobial aspiration.12 The rate of mucosal both primary and permanent teeth, killing, and antibody-dependent absorption of anesthetics is particu- as seen in this patient (Fig. 3).3,5,6J4 cell-mediated cytoxicity.9 larly rapid when open wounds and Dental therapy was directed at main- Neutrophils typically spend 6 days ulcerations are present; hence, the tenance of optimal oral care in order from the last stage of cell division abuse of topical anesthetics can lead to keep the periodontal tissues before entering the circulating to high blood levels and systemic healthy and delay the loss of alveolar blood. Daily injections of 30 g of effects such as cardiovascular compli- bone and teeth for as long as possi- G-CSF decreased the interval to 4.5 cations and central nervous system ble. Intensive preventive care was days, and 300 g daily further depression and excitation.13 advocated, with professional pro- reduced the transit time to approxi- Therefore, caregivers and patients phylaxis and scaling done every few mately 3 days.” The choice, dosage, should be instructed to use topical weeks when the CBC was high.15~16 and administration schedule of anesthetics with caution (not more The caregivers should be educated growth factor should be adjusted to than once every 30 minutes). At least about the role of dental plaque in the maintain the neutrophil counts above 20 minutes should elapse after an development and progression of 500/mm3 and to eliminate all infec- application before the patient eats a periodontal disease. They should be tions.*Our patient is currently on meal, to decrease the chance of acci- trained and periodically re-evaluated daily injections of 500 g of G-CSF. dental trauma. When the neutrophil in their ability to provide adequate The pediatric dentist who initially count recovers, the ulcerations heal, home care with meticulous plaque examined the patient was able to cor- usually without scarring.5.14 In the control through brushing and floss- relate the clinical picture with a possi- patient presented here, the boost in ing, and with chlorhexidine rinses as ble neutrophil problem, leading to neutrophil levels triggered by C-CSF an adjunct.
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