PEDIATRIC DENTISTRY/Copyright © 1987 by The American Academy of Pediatric Dentistry Volume 9 Number 2 SCIENTIFIC Oral manifestations of primary and acquired immunodeficiency diseases in children Penelope J. Leggott, BDSPaul B. Robertson, DDS Deborah Greenspan, BDS Diane W. Wara, MD John S. Greenspan, BDS, PhD Abstract nodeficiency, Nezelof’s syndrome, ataxia-telangiec- Immunodeficiencydiseases in children can have significant tasia, Wiskott-Aldrich syndrome) and phagocytic cell oral manifestations.Oral changesappear to dependon the nature defects. Immunological and clinical features of these of the host defect. Childrenwith IgA deficiency and hypogam- diseases have been reviewed in detail by Ammann maglobulinemiado not demonstratesevere oral pathologyor ab- (1984), Ammannand Wara (1975), and Buckley (1986). normalitiesin craniofacial development.Phagocytic cell defects Immune disorders are separated by system for pur- are associatedwith mucosallesions or rapidly progressiveforms of periodontaldisease. Candidiasis,recurrent aphthous ulceration, poses of discussion; however, defects in one immune and herpessimplex infections are reportedfrequently in children system may have major consequences for other sys- with T-cell and combinedimmunodeficiency disorders. Oralchanges tems. in pediatric acquiredimmunodeficiency syndrome are similar to Selective IgA deficiency is the most commondis- those seen in patients with primaryphagocytic cell and T-cell order of the immune system, and estimates of prev- defects, and can also includeparotitis and severe gingivitis. In alence range from 1 in 200 to 1 in 800. IgA levels are addition, humanimmunodeficiency virus infection in utero can less than 5 mg/dL, but other immunoglobulins are producean embryopathywith craniofacial abnormalities. usually normal or may be increased, and cell-me- diated immunity is normal. These patients show an increased incidence of sinopulmonary infection and may have an associated immunoglobulin subclass de- Immune defects in children, whether caused by ficiency in IgG2 and/or IgG4. Treatment is primarily primary immunodeficiency, by human immunode- symptomatic, and gamma-globulin therapy generally ficiency virus (HIV) infection, or by immunosup- is contraindicated. Patients with X-linked hypogam- pressive therapy, have profound effects on the oral maglobulinemia show symptoms of recurrent infec- tissues. In general, infection is the major cause of tions at an early age, an absence of B cells in periph- morbidity and mortality in these patients. Oral in- eral blood, IgG levels less than 200 mg/dL, and low fections are caused by organisms that normally are to absent levels of IgM, IgA, IgD, and IgE. The clinical either nonpathogens or are a minor component of the features of acquired hypogammaglobulinemia (common, oral microflora. Moreover, septicemia from an oral variable immunodeficiency) are similar to those of focus can cause a life-threatening infection in the X-linked hypogammaglobulinemia; however, B-cell immunocompromised host. This review will examine numbers usually are normal. Total immunoglobulins the oral features and dental management of children are less than 250 mg/dL. Both X-linked and acquired and young adults with primary and acquired im- hypogammaglobulinemia respond well to gamma- munodeficiency diseases. globulin treatment. Chronic mucocutaneouscandidiasis is a syndrome of Primary Immunodeficiencies skin and mucous membrane infection which may be Primary immune disorders considered here in- associated with absent lymphocyte proliferation to clude B-cell defects (selective IgA deficiency, hypo- Candida antigens, absent or delayed hypersensitivity gammaglobulinemia), T-cell defects (mucocutaneous skin test response to Candida antigens, impaired mac- candidiasis, DiGeorge’s syndrome), combined im- rophage function and, in some studies, neutrophil munodeficiency diseases (severe combined immu- chemotactic defects. Multiple endocrinopathies also 98 IMMUNODEFICIENCY DISEASES IN CHILDREN: Leggott et aL maybe present. The infecting agent is usually Candida A number of phagocytic dysfunction diseases albicans. B-cell function and antibody response to C. have been described. Clinical effects of phagocytic albicans typically are normal. Oral candidiasis and oth- cell defects range from mild skin infections to life- er oral mucosal lesions are a consistent feature of the threatening systemic infections. X-linked chronic gran- disease. Candidiasis also can be a feature of DiGeorge’s ulomatous disease is a severe form of phagocytic dys- syndrome (congenital thymic aplasia). This syndrome function. It usually is detected before 2 years of age, includes abnormal facies, hypoparathyroidism, con- based on marked lymphadenopathy, hepatospleno- genital heart disease, aplasia or hypoplasia of the thy- megaly, chronic draining lymph nodes, and suscep- mus, decreased numbers of T cells, and absent T-cell tibility to infections caused particularly by organisms function in peripheral blood. Thymus transplanta- normally of low virulence which have in common tion and/or thymic factor therapy have been suc- catalase positivity. Nonspecific references to oral sto- cessful in prolonging survival. matitis are commonto most case reports. Other symp- Severe combined immunodeficiency disease is inher- toms include rhinitis, osteomyelitis, and chronic diar- ited in X-linked recessive or autosomal recessive forms rhea. Mothers and sisters of affected boys may also and may be characterized by absence of both T-cell show abnormal neutrophil metabolism. However, the and B-cell function, resulting in susceptibility to in- neutrophil defect of female carriers is muchless pro- fection by any opportunistic organisms. Combined found, in vitro, than that of boys with chronic gran- immunodeficiency associated with the absence of the ulomatous disease, and unusual susceptibility to in- purine pathway enzymes adenosine deaminase and fections is uncommon. nucleoside phosphorylase is usually less severe, both clinically and immunologically. In the past, com- Acquired Immunodeficiency Syndrome bined-immunodeficient patients rarely survived more (AIDS) in Children than 1 year of age. Bone marrow transplantation has Human immunodeficiency virus infection has been successful in establishing some immunocom- been identified in increasing numbers of children petence and offers promise for an improved prog- with otherwise unexplained immune deficiency and nosis. Nezelof’s syndrome includes a diverse group of opportunistic infections of the type found in adults immunodeficient patients who exhibit the sequelae with AIDS.~ For the limited purposes of epidemio- of a variety of viral, bacterial, fungal, and protozoal logic surveillance, the Centers for Disease Control infections but do not show the specific clinical symp- (CDC)characterize a case of pediatric HIV infection toms or enzyme defects characteristic of other com- as a reliably diagnosed disease in children that is at bined immunodeficiency diseases. These patients have least moderately indicative of underlying cellular im- depressed T-cell function, but serum levels and func- munodeficiency, and with which no known cause of tion of the immunoglobulin classes are highly vari- underlying cellular immunodeficiency or any other able. Manypatients formerly classified in this cate- reduced resistance is reported to be associated. gory have adenosine deaminase or nucleoside A recent CDCreport (1986) described 231 AIDS phosphorylase deficiencies. patients under 13 years old, 59% of whomhad died. Immunodeficiencywith ataxia-telangiectasia is an au- Nineteen per cent were white, 60% black, and 20% tosomal recessive disorder associated with progres- Hispanic. Fifty-five per cent were male. Fifty-eight sive cerebellar dysfunction resulting in ataxia, slurred per cent were diagnosed with Pneumocystis carinii speech and nystagmus; telangiectasia involving the pneumonia; 19% with disseminated cytomegalovirus; bulbar conjunctivae, nose, ears, perioral area, and oth- 15%with candidal esophagitis; 6%with cryptosporid- er skin surfaces; recurrent sinopulmonary infections; iosis; 4% with Kaposi’s sarcoma; and 22% with other and, in about 70%of cases, selective IgA deficiency, opportunistic diseases. One hundred seventy-four which may be associated with IgG2 deficiency. In- (75%) pediatric patients came from families in which creased chromosomal breakage as well as abnormal 1 or both parents had AIDSor were at increased risk DNArepair following irradiation may be associated for developing AIDS; 33 (14%) had received trans- with the observed incidence of lymphoma in these fusions of blood or blood components before onset patients. Although careful supportive treatment has of illness, and 11 (5%) had hemophilia. Risk-factor prolonged survival, definitive therapy has not been information on the parents of the 13 (6%) remaining established. Wiskott-Aldrich syndrome is an X-linked patients is incomplete. recessive immunodeficiency consisting of eczema, The risk factors for pediatric HIVinfection vary thrombocytopenia, and recurrent infections. Serum depending on the age group. Most children with AIDS antibody patterns show low IgM levels and elevated are under 5 years of age. The primary risk factors are levels of IgA and IgE. Bone marrow transplantation perinatal. Infants born to womenwho are intrave- is under study in the management of these patients, but treatment approaches are not well defined. ’ Amrnann 1985; Oleske et al. 1983; Shannon and Ammann 1985. PEDIATRIC