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Oral Candidiasis in Pediatric HIV Patients

Posted on: Sunday, 24 April 2005, 03:00 CDT

Abstract

Oral candidiasis can be an early sign of illness or disease progression in HIV/AIDS and other immuno-compromised states. Oral lesions associated with fungal infections present in a variety of forms, including a few of previously unknown etiology. Diagnosing these variants of disease can be challenging because of their atypical clinical presentation. Moreover, the emergence of new Candida species, drug resistance and immature immune systems add to the complexity of this condition, especially in children.

Candida species reside as part of the normal flora of the oral cavity in about 40% of the general population known as carriers.1 In the event of immune suppression, there is a shift from commensalisms to an exponential increase in colonization, which eventually leads to clinical signs and symptoms of oral candidiasis (OC).

OC in children has been less well studied, with only limited numbers of individuals examined. However, between 20% and 70% of children with HlV infection or AIDS have been reported to show clinical signs of oral candidiasis.'~ It is also the first infection to appear in approximately half of all HIV-infected children. Esophageal candidiasis, an AIDS-defining illness, according to the CDC, is reported to develop in approximately 20% of children. The combination of an immature immune system and suppressed cellular immunity provides optimal conditions for rapid disease progression. As a result, pediatrie AIDS and associated infections have become a major challenge.

Oral Manifestations

Oral candidiasis may be present as clinically distinct forms, including pseudomembranous, erythematous and hyperplastic variants. Other lesions, such as linear gingival erythema, median rhomboid glossitis and angular cheilitis, are now also believed to be associated with candidiasis.3'4

The pseudomembranous type (thrush) is characterized by the presence of creamy plaques on any part of the oral mucosa (Figure 1). The white plaques can be removed easily, and may reveal a superficially hemorrhaging surface at times. Common locations for infection include the palate, gingiva, buccal mucosa and dorsum of the tongue.

Chronic hyperplastic candidiasis, or candidal leukoplakia, presents as white patches on the buccal mucosa that do not rub off. This condition is least common and somewhat controversial, as it is believed to be a combination of candidiasis superimposed on a leukoplakic lesion. The diagnosis is confirmed by the presence of pseudo-hyphae upon microscopic smear examination and resolution of the lesion after anti-fungal therapy (Figure 2).

When the tongue is affected, patchy depapillated areas appear on the dorsal surface (Figure 3). The palate can also be affected secondarily because of its close proximity to the tongue lesion.

Median rhomboid glossitis, or central papillary atrophy, a condition with a previously uncertain etiology, has now been associated with candidiasis.4 It is seen exclusively on the midline of the posterior dorsal aspect of the tongue and is asymptomatic. The erythematous mucosal changes are due to the loss of the filliform papillae, and the condition usually resolves following topical antifungal therapy.

Angular or labial cheilitis, characterized by fissuring at the corners of the mouth or lips, has also been implicated with a fungal origin and may appear either alone or in conjunction with any of the other forms4 (Figure 4). Chronic oral habits in children may spread this infection to adjacent sites, resulting in exfoliative lesions of the vermilion zone and perioral skin, creating a clinical pattern known as cheilocandidiasis.

Figure 1. Pseudomembranous candidiasis. Characterized by presence of white, creamy patches of plaque on oral mucosal surfaces.

(From New York Department of Health AIDS Institute's Clinical Guidelines Development Program Web site, www.hivguidelines.org.)

Figure 2. Hyperplastic candidiasis. Seen here as speckled white and erythematous areas that do not rub off.

Figure 3. Candida) glossitis. Characterized by central papillary atrophy of tongue.

Printed with permission: Neville BW, Damm DD, Allen CM, Bouquot JE. Oral & Maxillofacial Pathology, 2nd Edition, Philadelphia:W.B. Saunders, 2002.

Figure 4. Angular cheilltis. Seen as fissuring or hypo- pigmentation at angles of mouth. Fissuring can occur on lip as well (labial chelitis) and resembles "chapped lips."

(From New York Department of Health AIDS Institute's Clinical Guidelines Development Program Web site, www.hivguidelines.org.)

Figure 5. Atypical erythematous candidiasis. seen here as mild inflammation of maxillary anterior gingiva. Characterized by loss of stippling, mildly edematous and closely mimicking gingivitis.

Figure 6. Linear gingival erythema (LGE). seen as erythematous band 2-3mm in width along free gingival margin.

(From New York Department of Health AIDS Institute's Clinical Guidelines Development Program Web site, www.hivguidelines.org.)

Atropic or erythematous candidiasis (EC) appears clinically as a red lesion. The color intensity may vary from fiery red to a hardly discernable pink spot and is usually without clinical symptoms. It often presents as mild, localized inflammation of the gums and can be easily mistaken for gingivitis (Figure 5). An accurate diagnosis in such cases is difficult and can be further complicated in the presence of plaque and poor oral hygiene. Recent studies utilizing microscopic examination of mucosal swabs of such lesions report an overall increase in the prevalence of erythematous candidiasis.5 This is a shift from previous literature that suggests that pseudomembranous candidiasis is the most commonly occurring variant of oral fungal infections.6 It is unclear whether EC has been misdiagnosed in the past or simply underreported in children.3 There is also the possibility that perhaps EC lesions have a different clinical presentation in children than in adults.

HIV-associated gingivitis (HIV-G), a condition thought to be exclusive to HIV, has also been reported in other immunocompromised patients. It has since been renamed linear gingival erythema (LGE). As the name suggests, LGE is characterized by a linear erythematous band 2-3mm in width along the free gingival margin (Figure 6). Data from recent studies seem to suggest a fungal involvement that responds positively to anti-fungal therapy.3 Thus, the term "HIV- associated gingivitis" may yet be renamed "HIV- associated candidiasis." Regardless, the result is there may be a significant number of children with an undiagnosed variant of oral candidiasis.

The big question is, what are the long-term effects of undiagnosed (therefore untreated) oral fungal infections on the course of HIV/AIDS itself? Would treating the oral infection offer the body a better chance to deal with the HIV? The answers to these questions are largely unknown, although logic dictates that treating these infections may provide the body with a better chance of coping with the HIV. After all, morbidity and mortality from HIV infection are not because of the virus per se but result from the ensuing opportunistic and secondary infections.

Speciation

The majority of candidal infections in children and adults are caused by C. albicans; however, reports of the emergence of other novel species of Candida have begun to appear.7,8

Masia Canute, et al. recently evaluated 153 HIV-positive patients and found that 21% of these patients had non-C. albicans species. Similarly, Morace found that 25% of yeast species isolated from individuals with AIDS were non-C. albicans species, the most common being C. dubliensis, C. glabrata and C. krusei. Recent studies in children show that some species, exclusive to HIV/AIDS, have the ability to develop stable resistance to fluconazole in vitro and have significantly higher levels proteinase activity, a property considered a virulence factor in fungi.8

Management

When signs and symptoms of candidiasis are atypical, diagnosis is confirmed by exfoliative cytology, culture of the specimen obtained from the lesion and by a positive response to anti-fungal therapy.

Treatment of oral candidiasis in children involves the use of antifungal drugs, such as 1:500,000 nystatin suspension rinse. Clotrimazole oral troches may be prescribed for older children; the tablets are sucked five times a day. Candida can be resistant to all these forms of therapy, and even when responsive, may reappear soon after therapy is completed.7,9

TABLE 1

Candidal esophagitis usually requires hospitalization and intravenous therapy with amphotericin B. Drug resistance is often an undesirable outcome of therapy, and the goal of the dentist should be to develop preventive strategies, such as periodic regimens of chlorhexidine and fluoride rinses. Chlorhexidine has been shown to diminish the mucosal adherence of fungi, thereby eliminating the onset of infection.10 In addition, an aggressive recall/monitoring system should be developed for individual patients based on oral findings and the use of immunological markers to identify patients at risk.

The need for anticipatory guidance and communicating closely with the child's guardian and physician is paramount. Based on the immune status, pediatric HIV/AIDS can be classified into three categories. An immunological profile for each category has been adapted from the CDC and is presented in Table 1.

Discussion

Increased oral carr\iage of C. albicans is a common finding in HIVinfected patients. In a study done by Korting, "the microbiological recoveries of oral C. albicans from 62 HIV-infected adults were 57.5% for CDC stage I patients, 76.5% for stage II patients and 87.5% for stage III patients.11,12 Similarly, Fong, et al. found yeast carriage rates in HIV-positive individuals to be 67% for those with CD4-cell counts above 500 cells/l, 86% for patients with counts of 200 to 500 cells/l and 82% for patients with CD4- cell counts below 200 cells/l.11,13

Investigators have also demonstrated an increase in the intensity of candidal carriage in immunocompromised patients. The intensity of carriage is a quantitative measure of candidal species in the oral cavity. Its sensitivity can allow for early detection of infection even prior to the onset of mucosal changes. Normal values range from 350 to 400 colony forming units (CFU) per ml of saliva and show an increase with disease progression.11 Therefore, there has been considerable interest in recent years in using candidal carriage and intensity of carriage as early markers for disease progression in immunocompromised patients.

Although the basic pathogenesis of HIV infection is the same for adults and children, some laboratory findings are unique to children. For example, a CD4 count alone is not as reliable a marker of disease status because children tend to have higher and less consistent CD4 levels compared to adults, and a low CD4 count is often a late finding.14,15 There also are profound alterations in T- cell assays, hence, susceptibility to infections cannot always be correlated with immunological markers.

Because oral fungal colonization remains one of the most common opportunistic infections observed in both adult and pediatric HIV patients and is usually the first to appear, it can have a prognostic value16 independent of CD4 status or other more commonly used immunological markers. Interestingly, two AIDS-defining conditions of pneumocystis carinii pneumonia and intestinal lymphoma were associated with pseudomembranous oral candidiasis in two case reports."

Significance

Standard antibody testing is now available to determine an individual's HIV status at an early age. However, because of the expense of complex technology, health workers in developing countries, "where 95% of the world's pediatric AIDS cases are found," must rely on simple, inexpensive and early clinical tests for HIV infection.3 The monitoring of candidal carriage and colonization by dentists and other trained clinicians can lead to early diagnosis of HIV infection in both child and mother, or serve as a marker for disease progression.

Furthermore, prevention or early treatment of opportunistic oral infections may provide a better prognosis for the HIV infection, leading to an overall sense of well-being for these children with very special needs.

The authors thank Derek Park for his assistance with this article.

REFERENCES

1. Williams D, Lewis M. Isolation and identification of Candida from the oral cavity. Oral Diseases 2000;6:3-11.

2. Kline M. Oral manifestations of pediatric human immunodeficiency virus infection: a review of the literature. Pediatrics 1996;97(3):380-387.

3. Velegraki A, Nicolatou O, Theodoridou M, Mostrou G, Legakis NJ. Pediatric AIDS - related linear gingival erythema: a form of erythematous candidiasis? J.Oral Pathol. Med 1999;28:178-92. Munksgaard, 1999.

4. Neville BW, Damm DD, Alien CM, Bouquot JE. Oral & maxillofadal pathology, 2nd Edition. Philadelphia:W.B. Saunders Co., 2002.

5. Chen JW, Flaitz C, Wullbrandt B, Sexton J. Association of dental health parameters with oral lesion prevalence in human immunodeficiency virus-infected Romanian children. Pediatric Dentistry 2003;25(5):479-484.

6. McCarthy G. Host factors associated with HIV-related oral candidiasis. Oral Surg. Oral Med. Oral Pathol 1992:73:181-6.

7. Hicks MJ. Detection of fungal organisms in saliva from HIV- infected children: a preliminary cytologic analysis. Pediatric Dentistry 1998;20:3.

8. Brown D, et al. Identification of Candida dubliniensis in a study of HIV-seropositive pediatric dental patients. Pediatric Dentistry 2000;22:3.

9. Hauman, CHJ, et al. Oral carriage of Candida in healthy and HIV-seropositive persons. Oral Surg. Oral Med. Oral Pathol.l993;76:570-2.

10. Barasch A, Safford MM, Dapkute-Marcus I, Fine DH. Efficacy of chlorhexidine gluconate rinse for treatment and prevention of oral candidiasis in HIV-infected children: a pilot study. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Oral Endod 2004;97(2):204-7.

11. Vargas K, JoIy S. Carriage frequency, intensity of carriage, and strains of oral yeast species vary in the progression to oral candidiasis in human immunodeficiency viruspositive individuals. JCM 2002;40(2):341-350.

12. Korting HC. Clinical spectrum of oral candidosis and its role in HIV-infected patients. Mycoses 1989;32(Suppl.2):23-29.

13. Fong IW, Laurel M, Burford-Mason A. Asymptomatic oral carriage of Candida albicans in patients with HIV infection. Clin.Investig.Med 1997:20:85-93.

14. Leggott P. Oral manifestations of HIV infection in children. Oral Surg. Oral Med Oral Pathol 1992:73:187-92.

15. Pizzo PA, Wilfert CM. Markers and determinants of disease progression in children with HIV infection. The Pediatric AIDS Sena Workshop II. Journal of Acquired Immunodeficiency Syndrome and Human Retrovirology 1995;8:30-44.

16. Nicolatou O, Theodoridou M, Mostrou G, Velegraki A, Legakis NJ. Oral lesions in children with perinatally acquired human immunodeficiency virus infection. J.Oral Pathol.Med 1999:28:49-53. Munksgaard, 1999.

Shantanu Lal, B.D.S.; Steven Chussid, D.D.S.

Copyright Dental Society of the State of New York Mar 2005

Source: New York State Dental Journal

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