Classification, diagnostic criteria, and treatment recommendations for orofacial manifestations in HIV-infected pediatric patients Francisco J. Ramos-Gomez* / Catherine Flaitz** / Peter Catapano*** / Patricia Murray**** / Alan R. Milnes***** / Alejandro Dorenbaum****"*, and the Collaborative Workgroup on Oral Manifestations of Pediatric HIV Infection, Oral AIDS Center, University of California, San Francisco, San Francisco, California Orofacial manifestations in HIV-infected children The criteria for diagnosis of HIV-related oral lesions in adults are well established, but corresponding criteria in the pediatric population are not as well defined. The Collaborative Workgroup on the Oral Manifestations of Pediatric HIV Infection reached a consensus, based upon available data, as to the presumptive and definitive criteria to diagnose the oral manifestations of HIV infection in children. Presumptive criteria refer ro the clinical features of the lesions, including signs and symptoms, where «as definitive criteria require specific laboratory tests. In general, it is recommended that definitive cri teria be established whenever possible. Orofacial manifestations have been divided into three groups, 1) those commonly associated with pediatric HIV infection: 2) those less commonly associated with pediatric HIV infection; and 3) those strongly associated with HIV infection but rare in children Orofacial lesions commonly associated with pediatric HIV infection include candidiasis, herpes simplex injection, linear gingival erythema, parotid enlargement, and recurrent aphthous stomaritis In contrast, orofacial lesions strongly associated with HIV infection but rare in children include Kaposi's sarcoma, non-Hodgkin's lymphoma, and oral hairy leukoplakia Treatment recommendations, ‘specific for this age group, have been included for some of the more common HV-related orofacial ‘manifestations J.Clin Pediatr Dent 23(2): 85-96, 1999 Tanekco RamowGomez, DDS, MSc, MPH, Assistani Protessor, Department of Growth and Development, Schoo! fof Dentistry, University of Calor San Francisco, San Francisen, CA, USA. ++ Catherine Flatz, DDS, MS, Asoeinte Professor, Depart ‘ment of Stomatology, Division of Oral Pathology Univers exas Houston Dental Branch, Houston. TX. USA Catapano, DDS. Director of Pediattie Deatisty Bellevue Hospital, New York, NY, USA. Pauiie Murry. DMD, PhD, Associate Professor. Depart. ment of Penedonties, UMDNJ Dental School. Newark, NI USA. Alan R. Milnes, DDS, Dip Pacd, PRD, FRCD. Department of Paediatsic Dentistry; University of Toronto, Ontario. Canad, ‘s+80 Alejandeo Dorenbaum, MD, Assistant Professor, Depa ‘ment of Immunology, Division of Pediatrics, University of California, San Francisco, CA, USA, Address ll correspondence ta Br. Remos-Gomer at Box 0438, University of California, San Francieo, San Francsco, California SH143.008, USA Telephone 418/476.6825 FAX 4151476-0409 eon ramost@itsa ested, “he Journal af Clinical Peaiatrie Dentistry meroounn oe re A ste ora Soi es ee pag erga aes meio oae ee nea eer Soke legen Sean eo enmaia ae caterers restrain each ers a ee ee oer intimate eet nor epgeee fle rpeel iret ee © women. In a ‘Volume 23, Number 2/1999 85,Orofacial manifestations in HIV-infected children ‘Table 1. Consensus classification of orofacial lesions associated vith pectic HIV infection ‘Group 1 Lesions commonly associated with padiatne HIV infec candice Peeudomembranous Enythematous angular cnet Herpes simplex vita infection LUnear ging enythoma Parotid eniargement Recurrent aphtnous ulcers Minor Maer Herpetifon Group 2: Lesions less commonly associated with pediatric HIV infection. acter infections of orl tissues Panodontal diseases ‘Necrotizing ulcerative gingivitis Necrotang ulcerative peredonttis Necrotizing stomatitis Sebormec dermattis Vial afectons. Cytomegalovirus Human pasitomavirus Molusctm comagiosin Varicella oat0" virus Herpes-zoster Varicella Group 3: Lesions svongly associated with HIV infection but rare in chien Neoplasms ‘Kapos’s sarcoma and non-Hodgkin’ lymphoma ral hay teukoplania Tuberevosie rested ulcers ies of vital load in HIV-infected children during the first year of life, most patients had normal (high) CD4 ‘counts and were symptom free for the first 3-6 months despite high levels of viral replication as demonstrated by PCR.’ Early diagnosis of perinatally exposed infants and children is especially important because the inter: vals between infection, development of AIDS, and death are compressed in pediatric patients" Prior to the widespread use of combination drug therapy, approximately one-half of HIV-infected children became clinically symptomatic within the first year of life." Current estimates have decreased to one-quar ter, and the rest remain asymptomatic for an unknown number of years. Early diagnosis allows prompt institu tion of both multi-drug therapy (anti-retrovirals and protease inhibitors), which appears to be most effective when instituted early, and prophylactic therapy to fore- stall life-threatening opportunistic infections. ‘New advances in the development of antiviral drugs and multi-drug therapy with pediatric applications have been dramatic. However, to date, of the eleven drugs currently approved for the treatment of HIVIAIDS, only six are approved for pediatric use— 86 ‘The Journal of Cnical Pediatie Dentistry AZT (zidovudine), ddl (didanosine), d4T (stavudine), 37C (lamivudine), ritonavir, and nelfinavir. No other protease inhibitor has been approved for infants under the age of 2 years. Several studies have demonstrated that combination therapy including the use of a pro- tease inhibitor is associated with a substantial immuno- logic and virologic response." A retrospective review of 28 charts of children who received multi-drug com bination therapy containing a protease inhibitor showed marked reductions in viral load that correlated with improvement in CD4 cell counts, improved delayed hypersensitivity skin reactions, and clinical outcomes (weight gain). Larger studies are needed to define the optimal protease-inhibitor-containing drug combinations for children. Orofacial manifestations are among the earliest and ‘most common clinical signs of pediatric HIV disease. In March 1994 and May 1995, the Collaborative Work group on the Oral Manifestations of Pediattic HIV Infection met to develop guidelines for the diagnosis and management of HIV-related oral diseases in chil dren. The framework was adapted from the classifica tion system of the European Collaborative Clearing: house on Oral Problems Related to HIV Infection and the World Health Organization (WHO) Collaborating Centre on Oral Manifestations of the Human Immun. deficiency Virus!" The proposed guidelines, itis hoped, will facilitate early diagnosis of pediatric HIV infection and effective intervention by dental and med: ical professionals worldwide. CLASSIFICATION OF HIV-ASSOCIATED OROFACIAL LESIONS IN CHILDREN The classification of HIV-associated orofacial lesions in children is organized into three groups based on clini- cal experience and clinical studies limited to the pedi atric age group and on the frequency of association of these lesions with HIV infection (Table 1). Group 1 comprises those lesions commonly associated with pediatric HIV infection; Group 2 includes lesions less commonly associated with pediatric HIV infection; and Group 3 consists of those lesions strongly associated with HIV infection but rare in children. Both presump- tive and definitive criteria for diagnosis of those lesions are presented. By definition, presumptive cr diagnostic features applied during the clinical assess- ment of a patient, including the clinical characteristics of a lesion, stch as its appearance, color, texture, loca: tion, size, and reported symptomatology. Definitive cri teria include the application of presumptive criteria and a reasonable differential diagnosis, as well as inva: sive ot investigative laboratory tests to confirm the diagnosis, In general, it is recommended that a defini tive diagnosis be obtained for many of these orofacial manifestations, especially when the HIV status of a child is not known. Volume 23, Number 2/1999y Fig 1 Pseudomembranous candidiasis Fig, 2 Enythematous candidiasis The criteria, listed below, represent the consensus opinion of the Collaborative Workgroup on the Oral Manifestations of Pediatric HIV Infection. Further studies are required to evaluate the validity and relia bility of this classification system and the approach to sement. Group 1: Orofacial lesions commonly associated with HIV infection in children Candidiasis: Oral candidiasis is the most common oral lesion in children infected with HTV and is the first clinically observable manifestation of the disease. Studies! indicate that oral candidiasis occurs in up to 72% of all cases of pediatric HIV infection. Furthermore, candid asis may be of significant value in predicting the devel: ‘opment of AIDS in infected children." Three presen: tations of oral candidiasis have been documented in HIV-infected pediatric patients and are described below, Pseudomembranous candidiasis Presumptive criteria, Multifocal, nonadherent, ‘The Journal of Cinical Peatric Dentistry creamy white papules or plaques that can be wiped off with minimal pressure, leaving an erythematous surface (Figure 1). Pinpoint or petechial bleeding may be observed occasionally after removal of the superficial white coating. In general. these lesions are widespread and may be located anywhere in the oropharyn Defi al therapy is the principal defining nosis. However, cytologic smear or culture tests for the presence of Candida spp. may be helpful, particularly if the patient does not respond to antifungal treatment «due to potential resistance ive criteria. The patient’s response to antifun- riterion for di Exythemarous candidiasis Presumptive criteria. Multiple, flat, red patches of varying intensity, most commonly located on the palate and the dorsum of the tongue (Figure 2). Nonadherent, filmy white-to-creamy plaques may be seen concur rently with this form of candidiasis. Median shomboid slossitis, which is usually a red, smooth, depapillated patch on the mid-dorsal tongue, isa variant of this form of candidiasis. Tenderness or a burning sensation may be experienced. ‘Volume 29, Number 2/7999 87Orofacial manifestations in HIV-infected children Fig, § Heraes simplex virus infection Def assisted by detection of Candida spp. in culture or cyto- logic smear or by the patient’s response to antifungal treatment, five criteria, Definitive diagnosis may be Angular chelitis Presumptive criteria, Linear red or ulcerated fis- sures radiating from the corners of the mouth (Figure 3). Typically the lesions are bilateral, and multiple red papules may be found when the adjacent perioral skin is involved. Concurrent intraoral candidal involvement is a common clinical finding. These lesions are usually tender and slow to heal because of repeated manipula: tion from opening the mouth. Definitive criteria. Definitive diagnosis may be assisted by detection of intraoral Candida spp. in cul ture or cytologic smear or by the patient's response to antifungal therapies. A staphylococcal or streptococcal co-infection may be present in some cases. Herpes Simplex Virus infection Herpes simplex virus (HSV) infection is a common dhood infection that is not specifically related to HIY status. Both the primary disease, referred to as pri mary gingivostomatitis, and the secondary disease, referred to as recurrent HSV infection, may develop in children with HIV infection. Most studies do not dis. tinguish between the two forms of the disease. The reported prevalence for HSV infections in HIV-infect ed children ranges from 1.7% to 24%, Presumptive eriteria. Patients will exhibit fever and malaise, swollen and tender cervical lymph nodes, and intraoral and perioral lesions on the gingiva, hard palate, and vermilion border of the lips (Figures 4, 5). However, any mucosal site may be involved. Initially present as vesicles, these lesions rupture to become painful, irregular ulcers. Definitive criteria, Confirmation of a diagnosis of herpetic infection by laboratory methods is available but rarely used, The virus may be isolated in tissue cul 88 ‘The Journal of Ginical Pedatic Dentistry Fig. 6 Linear gingival enihema ture, Intact intraoral vesicles are rare. Cytologic exami nation reveals ballooning degeneration of infected epithelial cells and nuclear inclusion bodies, but it does not permit viral identification. Therefore, DNA hybridization is detinitiv diagnosis Note, Although non-HIV-infected children usually recover swiftly and completely from herpes simplex infection, HIV-infected children frequently have severe intraoral and extraoral lesions that may require hospi talization. Hospitalization is not routine for HSV infec tions in children, Moreover, the lesions tend tor the oral mucosa and on adjacent facial areas over pro- longed periods. Recurrent cases ate characterized by extensive lesions and marked crust formations on the vermilion border -ar gingival erythema Linear gingival erythema, which was formerly referred to as HIV gingivitis, is the most common form of HIV-associated periodontal disease in HTV- infected children, ‘The prevalence of this type of gin aivitis varies widely in different studies, ranging from (0% to 48%." The frequency of this particular lesion in children is not known but appears to differ among study populations Presumptive criteria. A fiery red, linear band 2 to 3 mm wide on the marginal gingiva accompanied by petechiae-like or diffuse red lesions on the attached tingiva and oral mucosa (Figure 6). The amount of ery thema is disproportionately intense given the amount of plaque present.” The erythema may be accompanied by bleeding during brushing and, in severe cases, by spontaneous bleeding, It is most notable on the buccal surfaces from cuspid to cuspid. Pain is rarely associated with linear gingival erythema, Definitive criteria. There are currently no known cri teria for obtaining a definitive diagnosis of linear gingi- val erythema. However. linear gingival erythema resists conventional plaque-removal therapies and oral Volume 23, Number 2/1998Fig, 7 Parotid enlargement hygiene measures, A similar clinical presentation ‘occurs in neutropenia, Thus, clinicians should review results of a recent complete blood count and differen: tial analysis of the white blood cells Note. The microbiology of linear gingival erythema is as yet unidentified. Based on adult population research studies, it is suspected that Candida spp. may be etiologically involved in linear gingival erythema in pediatric populations as well, but research on this pos sibility in children remains inconclusive Parotid enlargement Parotid swelling occurs in 10% to 30% of HIV infected children, although a study" of 9 infected chil dren found the condition in nearly half of all subjects. The condition generally occurs late in the course of HIV disease, HIV testing is recommended for pediatric patients with parotid swelling who are not known to be HIV positive. Parotid swelling has been associated with slower progression to AIDS; the median time to death has been reported as 3.4 years among patients with oral candidiasis and 5.4 years among those with parotid swelling Presumptive criteria. Unilateral or bilateral diffuse soft-tissue swelling resulting in facial disfigurement (Figure 7). May be accompanied by pain, and may be associated with lymphoid interstitial pneumonitis. Det criteria, No criteria have been established for the definitive diagnosis of parotid swelling, Recurrent aphth Recurrent aphthous ulcers occur in approximately 2% 0 6% of the adult HIV-infected population and are ‘The Journal of Cinical Pesiaric Dentistry Volu Orofacial manifestations in HIV-infected children ig. @ Major aphinous ulcer with permanent deformation of the tongue more common among HIV-infected children, especial: ly due to drugs such as ddl that may induce lesions. Recurrent aphthous ulcers occur in several different clinical forms, usually described as minor, major, and herpetiform, based on the size, lesions present umber, and duration of Minor recurrent aphthous ulcers Presumptive criteria. A small ulcer less than 5 mm in diameter covered with a pseudomembrane and sur rounded by an erythematous halo (Figure 8). Definitive criteria, A prompt response to steroid treatment confirms the diagnosis of recurrent aphthous ulcers. Note. Although aphthous ulcers may resemble some forms of candidiasis, they will respond to steroid treat ‘ment, unlike fungal infections. Major recurrent aphthous ulcers Presumptive criteria. Similar to those for minor recurrent aphthous ulceration; however, the mucosal lesions are much larger—sometimes 1 to 2.em in diam: eter —and may persist for weeks at a time, Major recur 3, Number 2/1989 89Fig, 10 Necrotizing ulcerative gingivitis rent aphtbous uleers are painful and may interfere with ‘cation and swallowing, They tend to occur on the soft palate, buccal mucosa, tonsillar area, and tongue (Figure 9), Definitive eri steroid agents, Note. Major recurrent aphthous ulcers have recent ly been associated with the use of HIV antiviral drug therapies such as ddC (zalcitabine), sia, Response to treatment with Herpetiform recurrent aphthous ulcers Presumptive criteria. Herpetiform lesions appear a clustets or erops of tiny recurrent aphthous ulcers, 1 to 2 mm in diameter, which may coalesce. Like major recurrent aphthous ulcers, herpetiform lesions tend to ‘occur in locations where they hinder eating and speak ing, such as the soft palate, buccal mucosa, tonsillar area, and tongue. Defini steroid agents Wve criteria. Response to treatment with Group 2: Orofacial lesions less com with HIV infection in children ly associated Bacterial infections of oral tissues Periodontal diseases HIV-infected children are more susceptible than adults to bacterial infections, especially those involving polysaccharide-encapsulated organisms (e.g.. Sirepto- eoccus pneumoniae). Bacterial infections in immuno: compromised children are frequently severe, deep: seated, and difficult to treat. Sinusitis and otitis media occur in children almost universally. Moreover. although HIV-associated periodontal diseases have been thought to appear less frequently in children than in adults, recent studies indicate that this assessment may be premature. A study of one cohort of 67 HIV- infected children in Newark, New Jersey, showed @ periodontal disease prevalence of 37%." and a study of 84 HIV-infected children in Rwanda reported peri ‘odontal disease as the most common oral manifesta 90 ‘The Journal of Clinical Padiaric Dentsty Fig. 14 Necrotizing ulcerative perodortiis tion.” Periodontal diseases are observed frequently in HIV-infected individuals in developing countries, and in children they seem to be associated both with immunodeficiency and with malnutrition, Necrotizing ulcerative gingivitis (NUG) Presumptive criteria The destruction of one or more interdental papillae accompanied by necrosis, uleera tion, and/or sloughing (Figure 10). Destruction is limit- ed to the marginal gingival tissues. In the acute stage (ie., acute necrotizing ulcerative gingivitis. or ANUG). the gingival tissues appear fiery-red and swollen, and are accompanied by yellowish-gray necrotic tissue that bleeds easily. Patients experience symptoms such as bleeding while brushing, pain, and a characteristic hal tosis, Definitive criteria. There are at present no definitive criteria for either NUG or ANUG. Diagnosis must be determined clinically. Responds to systemic antibiotic treatment and local debridement. Note. Symptoms may subside gradually over 3-4 weeks, but recurrences are common. NUG may repre: sent an initial stage of necrotizing ulcerative periodon: tits, Necrotizing ulcerative periodontitis (NUP) Presumptive criteria. Severe soft-tissue necrosis along with destruction of the periodontal attachment and bone over a short period of time. Paticnts often experience spontaneous gingival bleeding or bleeding when brushing, and severe, deep, aching pain in the jaw bone, In the most severe exposed. The final stage of necrotizing ulcerative peri ‘odontitis is marked by severe gingival recession result- ing from rapid bone loss and soft-tissue necrosis, (Figure 11). Definitive criteria, There are at present no definitive criteria for the diagnosis of necrotizing ulcerative peri codontitis, Note. Pocketing may be minimal because of simulta ‘eases, the jawbone may be Volume 23, Number 2/1900Fig, 12 Necoiiing siomatie| cous loss of both hard and soft tissues Tissuc destruc: tion may extend across the muco-gingival junction. NUP is chronic; ulceration will be seen during active periods but may be absent during dormant periods Necrotizing stomatitis (NS) Presumptive Acute and painful ulecronecrotic lesion on the oral mucosa (Figure 12). Underlying, bone may be exposed, or the lesion may penettate or extend into adjoining tissues. Definitive criteria, Histologic examination reveals the features of nonspecific ulceration. No specific microbial organism has been identified as the cause of necrotizing stomatitis, Note. NUG, ANUG, and NS each represents a dif ferent stage of what appears (0 be a single disease Necrotizing stomatitis occurs only in the most severe Seborrheic dermati Presumptive criteria, Erythema and scaling of the scalp, skin behind the cars, and nasolabial folds are par ticularly characteristic. Definitive criteria, No definitive criteria Note. HIV-infected children experience a wide vari ely of mucocutaneous manifestations. Some skin dis cases are duc 10 exacerbation of childhood dermatoses (c.g. atopic or sebortheic dermatitis) or are reactions to medications. Viral, bacterial, and fungal infections fare most common, Cutaneous Kaposi's sarcoma is extremely uncommon in children, Viral infections Cytomegalovirus Presumptive criteria. Lesions associated with cytomegalovirus may mimic a number of persistent oral ulcers, including aphthous ulcers, recurrent herpes simplex virus infection, necrotizing stomatitis, and ulceration NOS. Occasionally this infection may pre sent as a brightly erythematous gingivitis. ‘The Journal of Cineal Pesiatic Dertisry Volume 29, Number 2/1909 9 Orofacial manifestations in HIV-infected children oS Fig. 18 Human papliomavirusinfocton| Definitive criteria. A definitive diagnosis can be made through culture and biopsy Human papillomavirus (HPV) Presumptive criteria. Raised, irregular, flesh-colored lesions (warts) Definitive criteria. Excisional biopsy: However, diag nosis is generally based on clinical appearance Note, Children with HPV infection may develop verruca vulgaris, widespread flat warts, and condyloma ta acuminata (Figure 13). The presence of condylomata ina child should alert the clinician to the possibility of sexual abuse Molluscum contagiosum Presumptive criteria. A virally induced lesion of the skin, mucus membranes, and, rarely, the oral cavity Lesions are small, discrete and dome-shaped. Their color ranges fom pearly white to skin color (Figure In HIV-infected patients, the lesions may number in the hundreds Definitive criteria. When the core of the lesion is expressed and stained, molluscum bodies, which are virally transformed epithelial cells, can be seen. Varicella zoster virus Herpes zoster Presumptive criteria. Secondary disease or reactive tion of latent varicella-zoster virus. Herpes zoster is pri matily a condition that affects older adults and those who are immunocompromised. Pain or paresthesia is @ prodromal symptom. A well-delineated unilat tulopapular rash that becomes pustular and ulcerated follows Defi . Cytologic examination reveals virus-infected epithelial cells, Commonly confused with recurrent herpes simplex virus infections, herpes zoster can be definitively diagnosed through virus antigen typing with laboratory immunologic testsOrofacial manifestations in HIV-infected children Varicella Presumptive criteria. Primary infection with the varicella-zoster virus, one of the herpes viruses. A rash involving the head, neck and trunk may be accompa: nied by fever, chills, malaise and headache. The rash becomes vesicular, pustular and, finally, ulcerated. With successive waves of viremia, successive crops of new lesions appear. When the oral mucus membranes are involved, evanescent vesicles precede multiple shallow ulcers. Definitive criteria. Careful attention to history of exposure and type and distribution of lesions usually leads to clinical diagnosis, Xerostor Presumptive criteri reduced salivary flow rate: Definitive criteria, No definitive criteria exist for xerostomia. Note, Xctostomia is far more common in HIV. infected children than in HIV-infected adults. It may present not only as a result of HIV infection, but also as ‘a result of some medications, such as intravenous gamma globulin and antiviral drugs such as didanosine (adl). However, no discernible difference in the aver Dry mouth and severely age salivary flow rates has been found between HIV- infected and noninfected paticnts. Xerostomia may appear with or without parotid swelling Neoplasms ‘Kaposi's sarcoma and non-Hodgkin's lymphoma HIV-associated cancers such as Kaposi’s sarcoma and non-Hodgkin's lymphoma are far less common in children than in adults. The incidence of HIV-associat- ed cancers in symptomatic children is less than 2%. Recent research indicates that Kaposi’s sarcoma m: be caused by a herpes virus: however, the signif icance of this finding for HIV-infected pediatric patients has yet to be determined. (Oral hairy leukoplakia Presumptive eriteria, White, nonremovable lesions with corrugated surface appearing bilaterally on the lateral border of the tongue. These lesions may appear on the ventral and dorsal surfaces of the tongue and. ‘more rarely, on the buccal mucosa. Definitive eriteria. Presence of Epstein-Barr virus in the lesions, to be determined by laboratory histopathol- ogy and in situ DNA hybridization. If these studies can: not be performed, the lack of response to antifungal therapy may reinforce a presumptive diagnosis of hairy leukoplakia. ‘Note, Because other pathologies may present histo- 92 ‘The Journal of Clnical Pediatric Dentistry logical changes similar to those seen in hairy leuko plakia, the histological analysis alone is considered insufficient to establish a definitive diagnosis. The dif- ferential diagnosis of hairy leukoplakia must include number of other white lesions of the tongue and oral mucosa, such as idiopathic leukoplakia, hyperplastic candidiasis, white sponge nevis, geographic tongue, and lesions due to biting habits or trauma, ‘Tuberculosis-related uleers Co.infection with HIV and Mycobacterium tubercu- losis is common in underdeveloped countries.” In the United States, the association between HIV infection and tuberculosis (TB) was first described in areas with a high prevalence of HIV infection, ie, New York and Florida.” Secondary and primary TB lesions of the oral cavity are rare.” Presumptive criteria, Painless, non-healing wleera tion of the buccal mucosa, hard palate, gingivae and/or tongue. Occasionally TB may present with tongue involvement manifested as macroglossia or a mass in the cheeks." In most cases the mucosal lesions are dif ficult to recognize, but enlarged regional lymph nodes ‘may call attention to the process." Definitive criteria, A chest X-ray and a PPD test «with appropriate controls should be obtained when the disease is suspected. The diagnosis is usually confirmed ‘with acid-fast stains and cultures obtained from suspi: cious lesions and other sources (sputum, tracheal aspi: rates, broncheoalveolar lavages, gastric aspirates, lymph nodes, or tissue biopsies).™” Note. Children at risk are those living with adults who are at increased risk of exposure to and infection with TB, Because TB is rare in the United States, the clinician must consider this disease in the appropriate clinical setting. The PPD testis relatively insensitive in adults with HIV infection." No data are available for children, TREATMENT AND MANAGEMENT OF THE, MOST COMMON ORAL LESIONS IN HIV- INFECTED CHILDRE! Oral candidiasis Candidiasis should be treated promptly and thor- oughly with topical antifungal agents such as nystatin and clotrimazole (Table 2). Both oral and esophageal candidiasis have a high propensity to recur unless a fungal therapy is continued. Therapy is indicated to prevent the symptoms of pain, burning sensation, sore: ness, and dysgeusia that may occur. Topical antifungal treatment for oral candidiasis includes the use of nys tatin oral pastilles or clotrimazole oral troches; for both topical antifungals the recommended dosage is one 10- mg tablet dissolved in the mouth 3-5 times a day. If patient compliance is good, either of these regimens will effectively clear most oral lesions. However, Volume 28, Number 2/1999Orofacial manifestations in HIV-infected children Table 2. Agents for treatment of mucosal and systemic orfaesal infections recommended by Chicren's Hospital Oakland and the UCSF Ora [AIDS Center" OO (Group / Agent Usual daily dosage Frequency ‘Comments ‘Antifungals Nystatin 110.5 ml suspension Five tes/day Orally acministored agent 100,000 Limi vaginal tabiets 1 in ipple TID Topica! only Efieacy is varie Glotimnazole 101mg trecnes Five tmesiday Preferred intial therapy 100,000 Limi vaginal tablets t innippie TID For botte-ed infants Fiuconazole 2-5 moka Once daly Will absorbed and offactve in esophageal condiasis cases Ketoconazole 46 mang Once or twice daily Not absorbed in the presence of antacise Antivirals Reyeiovie 200-400 mg tabs oer Low dose recommended for HSV 400-800 mg tabs eit High dose for varicla zoster vis (VEN) Foseatnet 24-40 maka sh Very severe cases ony Antibiotics Amoxeilinsclaywanate 40 mala ost May cause dares ‘candamyein 20-30 markg Po ash For anaerobic infections 20-40 maka NIM c6-8H4 Metronidazole Somers wos For anaerobic infections 15.35 maiko PO ask ‘Augmentin because of the unpleasant flavor of some preparations and the number of times the tablets must be dissolved in the mouth, some patients may tend toward noncom: pliance, Clotrimazole is available as an oral suspension with dextrose content, and nystatin is available as an coral suspension with high sucrose content; howevet their cariogenic potential makes the advisability of these oral suspensions questionable. Topical fluoride should be used if these medications are administered for long periods, In children, systemic therapy has the advantage of cone daily dose (fluconazole). Fluconazole and keto- conazole are systemic antifungal medications, usually used for pharyngeal lesions, for lesions that do not respond to topical agents, or for esophageal candidiasis, which may develop in patients already receiving nys- tatin or clotrimazole for oral candidiasis (Table 2) Periodontal disease HiV-related periodontal diseases (NUG, ANUG NUP, and NS) should be treated with plaque removal scaling, and root planing. Irrigation with 10% povi- done-iodine is also recommended when the disease is, in its acute stage. Patients should rinse daily with chlorhexidine mouth rinse as an adjunct to good oral hygiene. The therapeutic response may vary, and ‘Te Journal of Clnial Pediatric Dentistry relapses are common. It is recommended that patient with pain and severe acute lesions (generally ANUG. ‘and NS) be treated with antibiotics, such as metronida ole, amoxicillin/clavulanate potassium, or clindamycin (Table 2). Herpes Simplex ‘Most herpetic lesions, even in HIV-infected children, are self limiting. When lesions do persist, however, they can be treated with systemic antiviral agents such as acyclovir. Oral acyclovir may be indicated for treat ment of intraoral lesions and herpes labialis. Foscarnct, (trisodium phosphonoformate hexahydrate) has proven to be an effective treatment for resistant her petic lesions in adults and children (Table 2) Parotid swelling Parotid swelling is usually left untreated. In extreme cases, however, parotid swelling may be treated with anti-inflammatory agents, analgesics, antibiotics or, ‘occasionally, steroids. Xerostomi Xerostomia may be treated with a variety of salivary stimulants, such as sugarless gum or candy, to relieve symptoms. Artificial saliva rarely offers significant Volume 23, Number 2/1989 93Orofacial manifestations in HIV-infected children relief, but pilocarpine may be effective if treatment is managed in collaboration with the patient’s pediatri cian. Children with decreased salivary flow should be advised to use fluoride rinses or gels to prevent caries and should also be monitored for Candida spp. Recurrent aphthous ulcers ‘The severity and location of recurrent aphthous ulcers will dictate appropriate treatment. Topical steroid therapy should be the first choice: an applica tion of fluocinonide (0.05% ointment mixed 1:1 with plain Orabase) or, if fluocinonide proves ineffective, clobetasol propionate (0.05% ointment mixed 1:1 with plain Orabase). Dexamethasone elixir used as a mouth: wash or gargle can prove an effective alternative, ‘Thalidomide has also been used in adults with HTV to treat aphthous ulcers, and has been linked to a decrease in their viral load, However, this drug has not been test- cd in children. Reinforcement of good oral hygiene is useful, and in some cases recurrent aphthous ulcers can go untreated Oral hairy leukoplakia Because hairy leukoplakia lesions are usually asymptomatic, treatment may be considered elective. ‘The lesion might change in appearance, and a few patients complain of discomfort, Lesions respond to treatment with acyclovir, but they tend to recur when tweatment is discontinued SUMMARY In the last few years, the implementation of new and different drug protocols has allowed HIV-infected chil dren to be maintained alive and asymptomatic, From the AZT guidelines for pregnant women, which have reduced vertical transmission to 8%, to the new multi drug combination therapy for children, which has increased their CD4 counts and reduced viral loads to undetectable levels, improvements abound. Antiretro- viral therapy is constantly developing and changing, and recent advances have prolonged wellness and fed ‘optimism for children and adolescents, Orofacial manifestations should be considered the earliest clinical sign of HIV infection and a good indi- cator of disease progression in children, Since the mouth is easily examined, certain oral signs may be used to increase early detection and provide a basis for more aggressive and appropriate treatment of HIV infection, improving the overall health outcome of this vulnerable population, Unlike most infections, HIV produces a chronic infection requiring treatment for an indefinite period, possibly the entire life of the individual. Multiple fac- tors will dictate the most appropriate therapeutic reg. imen for an individual and influence that regimen’s ong-term impact on drug resistance and effectiveness. Clearly, more clinical trials are needed, both to learn 96 ‘Tre Journal of Cinicl Pediatric Dentisry how to control HIV infection and to test the pharma. cokinetics and toxicity of drugs in children and ado- lescents, ACKNOWLEDGMENTS Workgroup members: Francisco J. Ramos-Gomez, DDS, MSc, MPH, Chair and Coordinator, Assistant Professor, Department ‘of Growth and Development, Division of Pediatrics, School of Dentistry, University of California, San Francisco. Peter Catapano, DDS, Director of Pediatric Dentistry. Bellevue Hospital, New York Alejandro Dorenbaum, MD, Assistant Profs Department of Immunology, Division of Pediatrics, University of California, San Francisco. Fred S. Ferguson, DDS, Department of Children’s Den- tistry, School of Dental Medicine, SUNY Stony Brook, Catherine M. Flaitz, DDS, MS, Associate Professor Department of Stomatology, Division of Oral Pathology, University of Texas Houston Dental Branch, Franklin Garcia-Godoy, DDS, MS, Professor, Depart ment of Pediatrie Dentistry, University of Texas, San Antonio. John J. Jandinski, DMD, Associate Professor, Depart ‘ment of Oral Pathology, Biology and Diagnostic Sci ences, UMDNJ Dental School, Newark. Masakazu Ikeda, DDS, Director, Department of Den: tistry, Kanagawa Children’s Medical Center, Yoko: ama, Japan, Tatyana Trova, MD, PhD, Senior Research Associate. Russia AIDS Center, Moscow. Daniel Johnson, MD, Director, Pediatrie HIV Program, Department of Pediatrics, University of Chicago. Penelope J. Leggott, BDS, MSc, Chait of Pediatric Den- tistry and Associate Dean of Students, Health Sci ences Center, University of Washington, Seattle ‘Ann Madigan, DDS, Pediatric Dentist, West Harrison, New York. Alan R. Milnes, DDS, Dip Paed, PhD, FRCD, former Department of Paediatric Dentistry, University of Toronto, Ontario, Canada. (Practicing in Vancou ver). Patricia Murray, DMD, PhD, Associate Professor, Department of Periodontics, UMDNJ Dental School, Newark, Ann Petru, MD, Assistant Clinical Professor, Depart ment of Pediatrics, Children’s Hospital, Oakland, CA, Vadim Pokrovsky, MD, Professor and Chief, Russia AIDS Center, Moscow. Graham Roberts, Reader, Department of Children’s Dentistry, Guys Tower, London. Grace Sampaio-Teles, DDS, Department of Pediatric Dentistry, UFRJ Brasil, Rio de Janeiro. Volume 23, Number 2/1999Orofacial manifestations in HIV-infected children Evelyn Shechy, DDS, Department of Pediatrie Den- tistry, Guys University, London, England. George Thomas, DDS, Chair, Department Pediatr Dentistry, Howard University, Washington, DC. Nilza Toledo, DMD, FAAPD. 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