Oral Manifestations of Pediatric HIV Infection:

1
Oral Manifestations of Pediatric HIV Infection

• Clinical Characteristics, Diagnosis, Treatment
  Recommendations and Disease Significance

2
Disease Pattern Differences in Pediatric and
Adult HIV Infection

• Narrower spectrum of infectious diseases in
  children
• More vulnerable to recurrent bacterial infections
• More susceptible to central nervous system
  disorders
• Increased risk for HIV-lymphoproliferation
• Decreased risk for malignancies
• Endocrine and metabolic impact on growth and
  development
• Behavioral and emotional problems due to chronic
  illness

3
Diagnosis of Pediatric HIV Oral Lesions

• Clinical examination is important because history
  is often unknown or incomplete
• Rely on noninvasive procedures for initial
  diagnosis and treatment
• Treatment often requires modification and
  individual customization
• Successful management necessitates care giver
  involvement and understanding
• Diagnosis should be re-evaluated, if treatment is
  not effective

4
Oral Manifestations of Pediatric HIV Infection

• Most children will have at least one oral lesion
• Infectious diseases bacterial, viral and fungal
• Most neoplasms are EBV driven lymphoma,
  leiomyoma and leiomyosarcoma
• Immunologic disorders aphthous ulcers,
  parotitis, lymphadenopathy, thrombocytopenia and
  allergic reactions
• Iatrogenic diseases are caused by drug side
  effects
• Dental diseases Dental caries, enamel
  hypoplasia, over-retained teeth, delayed eruption
  of teeth

5
Oral Candidiasis in Children

• Common opportunistic fungal infection, affecting
  up to 72 of HIV infected children
• Cause Candida species, usually Candida albicans
• Contributing factors Immune suppression,
  xerostomia medications, oral appliances, poor
  oral hygiene
• Forms Pseudomembranous, erythematous
  hyperplastic candidiasis, angular cheilitis,
  median rhomboid glossitis, cheilocandidiasis
• Site Lips and oropharyngeal mucosa
• Signs Symptoms Red or white patches, erosions,
  burning sensation, sore throat, taste alterations
• Diagnosis Clinical findings, culture, cytology,
  biopsy

6
Oral Candidiasis in Children
7
Rx Oropharyngeal Candidiasis

• Nystatin susp 100,000-500,000 U 4 times daily
  for 14-21 days
• Clotrimazole susp, troche 10 mg 4-5 times daily
  for 14-21 days
• Fluconazole susp, tab 3-6 mg/kg daily for 14-21
  days
• Ketoconazole susp, tab 5-10 mg/kg in 1 or 2
  doses for 14-21 days
• Itraconazole susp 2-5 mg/kg daily for 14-21 days
• Amphotericin IV 0.5-1.0 mg/kg/d
• Antifungal ointment or cream for lips, if needed

8
Parotitis in Children

• Lymphocyte-mediated salivary gland disease
  observed observed in about 30 of children
• Cause CD8 infiltrate HIV, EBV genetic
  predisposition
• Median age of onset 5.4 years
• Site Parotid and submandibular glands may
  affect lungs and other organs
• Signs Symptoms Diffuse facial swelling, may be
  tender, xerostomia, cervical lymphadenopathy,
  enlarged palatine tonsils
• Diagnosis Clinical findings, advanced imaging,
  aspiration or labial lip biopsy
• Complication Bacterial sialadenitis, lymphoma

9
Parotitis in Children
10
Treatment of Parotitis

• Caries and gingivitis prevention Topical
  fluorides, clorhexidine gluconate oral rinse
• Pain management Nonsteroidal anti-inflammatory
  drugs (NSAIDS)
• Ibuprofen 5-10 mg/kg q 4-6 h (max 40 mg/kg/d)
• Naproxen 5-10 mg/kg q 8 h (max 1500 mg/d)
• Saliva stimulants Pilocarpine, cevimeline
  hydrochloride
• Severe facial swelling Prednisone surgery, if
  large cystic lesions are present
• Bacterial sialadenitis Antibiotics - clindamycin

11
Herpes Simplex Infection in Children

• Common viral infection affecting up to 24 of
  children
• Transmission Direct contact, asymptomatic viral
  shedding in genital fluids and saliva
• Median age of onset 5 years
• Site Orofacial, nasal and esophageal region
• Signs Symptoms Painful gingivitis, recurrent
  persistent ulcers intraorally vesicles and
  crusted ulcers on lips and skin
• Non-nutritive sucking habits increase risk for
  ocular and digital infection
• Diagnosis Clinical, culture, PCR, cytology,
  biopsy

12
Herpes Simplex Infection in Children
13
Treatment of HSV Infection

• Systemic Antiviral Medications
• Zovirax, generic (acyclovir) 15 mg/kg, 5
  times/day
• Famvir (famciclovir) Not approved for pediatric
  use
• Valtrex (valacyclovir) Not approved for
  pediatric use
• Foscavir (foscarnet), if resistant (6.4 HIV) -
  IV
• Topical Antiviral Agents Not usually recommended
• Denavir (penciclovir) 1 cream
• Zovirax (acyclovir) 5 ointment
• Abreva (docosanol) 10 cream (OTC)

14
Cytomegalovirus Infection in Children

• Congenital Infection 4.5 - 21 of HIV-exposed
  infants
• Transmission Viral shedding in genital fluids,
  breast milk, urine and saliva blood, organs
• CMV disease 8-18 retinitis, pneumonitis,
  colitis, mucocutaneous ulcers, neuropathy,
  encephalopathy
• Site Oral and esophageal regions, salivary
  glands
• Oral S/S Persistent ulcers, gingivitis, pyogenic
  granuloma enamel hypoplasia - congenital
  disease
• Diagnosis Culture, PCR, biopsy
• Treatment Ganciclovir, foscarnet, cidofovir

15
Cytomegalovirus Infection in Children
16
Herpes Zoster in Children

• Prevalence 2-6 HIV infected children
• Cause Reactivation of varicella-zoster virus
• Median age 7.6 yrs but common under 5 yrs
• Site 5 in the head neck region CN5 CN7
• Signs Symptoms Vesicles, coalescing ulcers,
  thick crust on skin, follow dermatome and stop
  at midline pain, fever and headache 4 are
  bilateral
• Diagnosis Clinical, culture, cytology
• TX Acyclovir, valacyclovir, famciclovir,
  foscarnet
• Complication Scarring, blindness, secondary
  infection, disseminated disease

17
Herpes Zoster in ChildrenWRONG PICTURE !
18
Aphthous Stomatitis in Children

• Pediatric prevalence Up to 16 common oral
  lesion
• Cause Localized immune dysfunction
• Predisposing factors Trauma, hematologic
  disorders, nutritional deficiencies, allergies,
  oral appliances
• Variants Minor, major and herpetiform
• Site Primarily affects nonkeratinized
  oropharyngeal mucosa, esophagus
• S/S Painful recurrent ulcers, multifocal
  pattern, increase in the major variant, may
  result in scarring
• Diagnosis Clinical culture and biopsy, if
  persistent

19
Aphthous Stomatitis in Children
20
Treatment of Aphthous Ulcers

• Pain management Topical anesthetics and coating
  agents, systemic analgesics
• Ulcer management
• Kenalog (triamcinolone) in Orabase 0.1
• Fluocinonide gel or ointment 0.05
• Clobetasol gel or ointment 0.05
• Dexamethasone elixir 0.5 mg/5 mL
• Beclomethasone dipropionate1-2 puffs/3X/d
• Prednisone (2mg/kg/d or 20 - 60 mg) 5-7 d
• Thalidomide (50 - 200 mg/d)

21
Molluscum Contagiosum in Children

• Common skin infection caused by the poxvirus
• Associated with low CD4 counts
• Predisposing factors Trauma and dermatitis
• Transmission Direct contact
• Site Facial skin and genital region
• Signs Symptoms Multiple, pearly-white nodules
  with umbilicated center and erythematous border
• Diagnosis Clinical, cytology, biopsy
• TX Surgical - curettage, cryotherapy, excision
  Topical cantharidin, cidofovir, imiquimod

22
Molluscum Contagiosum in Children
23
Periodontal Diseases in Children

• Disease Classification and Prevalence
• Linear gingival erythema (LGE) 0 - 38
• Necrotizing ulcerative gingivitis (NUG) 0 - 5
• Necrotizing ulcerative periodontitis (NUP) 0 -
  5 (most common oral lesion in Africa)
• Necrotizing stomatitis (NS) Unknown
• Conventional gingivitis 50 - 97
• Periodontitis modified by systemic disease
  Unknown

24
Linear Gingival Erythema in Children

• Pediatric prevalence Up to 38 common oral
  lesion
• Cause Unknown but Candida sp, especially C.
  albicans, C. dublinienesis has been implicated
• Site Usually multiple teeth but may be localized
• Signs Symptoms Fiery red band 2-3 mm wide on
  marginal gingiva petechiae or diffuse erythema
  on adjacent mucosa bleeding is uncommon pain is
  rare
• Note Erythema is disproportional to amount of
  plaque
• Diagnosis Clinical nonresponsive to oral
  hygiene
• TX Plaque and caries control antifungal
  medications

25
Linear Gingival Erythema in Children
26
Necrotizing Ulcerative Gingivitis

• Pediatric prevalence 0 - 5 uncommon oral
  lesion
• Cause Fusiform-spirochete bacteria
  Gram-negative
• Predisposing factors Stress, immune suppression,
  smoking, malnutrition, pre-existing gingivitis
• Age Adolescents in US young children in
  developing countries, especially Africa
• Site Anterior gingiva to widespread
• Signs Symptoms Punched out, ulcerated
  papillae, bleeding, pain, lymphadenopathy, fetid
  odor, fever
• Diagnosis Clinical, biopsy of persistent lesions

27
Necrotizing Ulcerative Gingivitis
28
Necrotizing Ulcerative Periodontitis

• Pediatric prevalence 0 - 5 uncommon oral
  lesion
• Cause Fusiform-spirochete bacteria
  Gram-negative
• Predisposing factors Immune suppression,
  smoking, malnutrition, stress, pre-existing
  periodontitis
• Age Usually adolescents
• Site Lower anterior gingiva to widespread
• S/S Features of NUG, rapid bone loss, necrosis
  and sequestration, tooth loss
• Diagnosis Clinical and radiographic, biopsy, if
  persistent lesions

29
Necrotizing Ulcerative Periodontitis
30
Necrotizing Stomatitis in Children

• Pediatric prevalence Uncommon oral disease
• Cause Multifactorial including bacterial,
  fungal, viral
• Predisposing factors Severe immune suppression,
  neutropenia, malnutrition
• Site Often contiguous with gingival lesions but
  may occur at any mucosal site
• Signs Symptoms Persistent, destructive ulcers
  with thick, tenacious pseudomembrane single or
  multiple very painful
• Diagnosis Clinical, culture, biopsy, if
  persistent
• Complication Weight loss and wasting disease

31
Necrotizing Stomatitis in Children
32
Necrotizing Periodontal Diseases

• Management
• NUG/NUP Debridement, 10 povidone-iodine,
  extraction of involved primary teeth,
  chlorhexidine oral rinse, antifungal and
  antibiotic therapy
• Antibiotics Clindamycin 20-30 mg/kg/d or
  penicillin VK 25-50 mg/kg/d plus metronidazole 30
  mg/kg/d or amoxicillin clavulanate 40 mg/kg
• Systemic analgesics for pain
• Periodic dental visits Every 3-4 months

33
Conventional Gingivitis in Children

• Conventional gingivitis mimics LGE
• Decreased gingival health is associated with
  advanced HIV disease and decreased CD4
  percentages
• Higher plaque and gingival indices associated
  with candidiasis
• Leukopenia and anemia mask the clinical signs of
  erythema

34
Lymphadenopathy in Children

• Prevalence Cervical lymphadenopathy gt 50
• Cause HIV and EBV lymphoid replication
• Site Generalized submandibular, cervical and
  pharyngeal tonsils
• S/S Bilateral, persistent, diffuse enlargement
  nontender no erythema of the skin gt 0.5 cm at
  more than one site
• Significance Positive predictor of HIV survival
• Mimics viral, bacterial infection, lymphoma
• Treatment None required aspiration biopsy and
  advanced imaging with significant enlargement

35
Lymphadenopathy in Children
36
Hairy Leukoplakia in Children

• Pediatric prevalence 2 - 3 uncommon oral
  lesion
• Cause Replicating and latent EBV, multiple
  strains and recombinant variants
• Site Primarily lateral border of the tongue
• Signs Symptoms Filmy to shaggy adherent white
  plaques, asymptomatic, taste abnormalities,
  burning sensation lesion waxes and wanes
• Concurrent disease Candidiasis
• Diagnosis Clinical, cytology, biopsy, PCR or in
  situ hybridization

37
Hairy Leukoplakia in Children
38
Oral Warts in Children

• Skin lesions are common but oral warts are rare
  (lt1)
• Cause Human papillomavirus (HPV)
• Transmission Direct contact, vertical infection
• Predisposing factor Inflammatory skin disorders
• Site Perioral skin, vermilion, oral and nasal
  mucosa
• S/S Spiky or flat, papillary or stippled, white
  papules and nodules usually multiple or florid
  in number
• Diagnosis Clinical, biopsy, HPV-typing
• TX Excision, laser ablation, cryotherapy when
  localized

39
Oral Warts in Children
40
Thrombocytopenia in Children

• Pediatric prevalence Up to 18 during disease
  course
• Cause Antibody-mediated, bone marrow failure
• Site Oropharyngeal and nasal mucosa, skin
• S/S Gingival bleeding, petechiae, purpura,
  hematoma nosebleed
• Diagnosis Complete blood count, including
  platelet count, thrombopoietin
• TX HAART regimens, interferon-?, steroids, IVIG,
  transfusion

41
Thrombocytopenia in Children
42
Cancer in Children

• Prevalence 2 of HIV infected children
• Cause Viral-associated, EBV, HHV-8, HPV
• Median age 4.3 years - vertical 13.4 years -
  blood
• Types from Childrens Cancer Group (1982-97)
• Non-Hodgkins lymphoma (65)
• Leiomyosarcomas, leiomyomas (17)
• Leukemia, lymphoblastic and myeloid (8)
• Kaposis sarcoma (5)
• Hodgkins lymphoma (3)
• Vaginal carcinoma, tracheal neuroendocrine (2)

43
Lymphoma in Children

• Prevalence lt 2 most common malignancy
• Type Most are high-grade non-Hodgkins lymphoma
• Cause EBV, HHV-8 and immunosuppression
• Median age 5.5 years (1.1-19.4 yrs)
• Site 80 are extranodal GI and CNS
• Oral site Tonsils, palate and gingiva
• S/S Rapid growth, diffuse pink to red mass,
  ulceration pain paresthesia tooth mobility
  and displacement bone loss
• Diagnosis Biopsy, advanced imaging, tumor
  staging
• TX Multiagent chemotherapy /- radiation

44
Lymphoma in Children
45
Kaposis Sarcoma in Children

• Pediatric prevalence Rare except for Africa
• Cause HHV-8 and immune suppression
• Rare vertical transmission, except Africa
• Form Lymphadenopathic type with or without
  diffuse skin lesions rare oral involvement
• Oral site Palate and gingiva
• S/S Red to purple macule or nodule single or
  multiple, usually asymptomatic
• Diagnosis Biopsy and tumor staging
• TX HAART regimens, chemotherapy

46
Kaposis Sarcoma in Children
47
Cutaneous Lesions in Children

• Prevalence gt 80 of HIV infected children will
  have at least one mucocutaneous lesion
• Infectious diseases account for 66
• Inflammatory disorders account for 33
• Similar prevalence as oral lesions in these
  children
• Besides herpetic infections, several lesions are
  potentially contagious to the health care
  provider
• Impetigo
• Tinea corporis
• Scabies

48
Impetigo in Children

• Type Contagious, superficial bacterial infection
• Cause Staphylococcus aureus, streptococci
• Transmission Direct contact
• Site Usually the face but any body surface
• Signs Symptoms Vesicles, pustules or bullae
  with a red base and covered by honey-colored
  sticky crust lymphadenopathy may become
  hyperpigmented
• Diagnosis Clinical, culture
• TX Mupirocin (Bactroban) ointment for isolated
  lesions systemic antibiotics if widespread

49
Impetigo in Children
50
Tinea Infections in Children

• Type Superficial fungal infection (ringworm)
• Cause Dermatophytes and immune defect
• Distribution Tinea pedis (feet) tinea corporis
  (face, body, limbs) tinea capitus (scalp) tinea
  cruris (groin)
• Signs Symptoms Annular lesions with red,
  scaly, advancing front alopecia when scalp is
  involved
• Diagnosis Clinical, cytology
• Significance Severe and persistent infection
• TX Topical or systemic antifungal medications
  refer to pediatrician or dermatologist

51
Tinea Infections in Children
52
Antiretroviral Regimens in Children

• HAART 2 nucleoside analogue reverse
  transcriptase inhibitors (NRTI) 1-2 protease
  inhibitor (PI) or 1non-nucleoside reverse
  transcriptase inhibitor (NNRTI)
• NRTI oral side effects Oral ulcers (ddC), sore
  throat (ABC), xerostomia (ddI), anemia,
  neutropenia (AZT)
• PI oral side effects Taste perversions,
  xerostomia, exfoliative cheilitis, circumoral
  paresthesia, thrombocytopenia
• NNRTI oral side effects Lichenoid reaction,
  erythema multiforme major
• Drug Interactions and dentistry Midazolam,
  triazolam, metronidazole, meperidine

53
Antiretroviral Regimens in Children
54
Dental Considerations in Children

• Poor compliance with therapies
• Oral effects of medications dry mouth, vomiting,
  taste alterations, sucrose and alcohol content
• Symptomatic orofacial lesions
• Referred pain Sinusitis, otitis media,
  neuropathies
• Compromised airway and pulmonary function
• Poor motor skills neuropathy, encephalopathy
• Hematologic disorders Cytopenias
• HAART regimens potential drug interactions
• Exposure to a variety of infectious diseases