B.Chanaram First year M.D.S Dept.

of pedodontics and preventive dentistry 18th August 2011

Autoimmunity Vs immunodeficiency
Autoimmunity

system loses its sense of self

Immunodeficiency

the system errs by failing to protect the host

Immunodeficiency diseases
Primary immunodeficiencies Deficiency in adaptive immunity

Combined T and B cell deficiency Severe combined immunodeficiency Wiskott-Aldrich syndrome Ataxia-telangiectasia T cell deficiency DiGeorge syndrome Defects in the MHC B cell deficiency Brutons X-linked Agammaglobulinemia Decrease in certain classes of Ig
Common variable immunodeficiency Selective immunoglobulin deficiency Hyperimmunoglobinemia E syndrome

Deficiency in innate immunity Cehdiak-higashi syndrome

 Secondary Immunodeficiency
Infections

HIV Acute severe viral infections Immunosuppressive drugs Cytotoxic drugs Radiotherapy

Drug induced

 Primary or congenital immunodeficiency

Secondary or acquired immunodeficiency,

Severe combined immunodeficiency

Children born with SCID are profoundly immuno

compromised With out treatment most die of infection before the age of 1 year Few or No circulating B and T cells leaving them susceptible to infection Oral complications include

Aphthous like ulcerations Candidiasis Herpetic infections

WISKOTT-ALDRICH SYNDROME (WAS)

is an X-linked disorder characterized by lymphocytes

and platelets that are faulty due to an altered cell surface glycoprotein they share The T cells have a uniquely abnormal appearance due to a cytoskeletal defect The classic clinical features include a
microcytic thrombocytopenia,

severe eczema, and

pyogenic and opportunistic infections

WISKOTT-ALDRICH SYNDROME (WAS)

WISKOTT-ALDRICH SYNDROME (WAS)

 Clinical manifestations shortly after birth include

petechiae,bruisihg and bloody diarrhea Complications such as otitis media . Pneumonia from bacteria and skin infections are frequent problems

Ataxia -telangiectasia

Ataxia-telangiectasia
The ataxia usually begins in infancy and is progressive.
Telangiectasias of the skin and eyes become apparent

between 3 and 6 years of age clinically manifested by recurrent and chronic sinopulmonary infections

 the patients are extremely sensitive to ionizing

radiation Hence, radiographic examinations should not be performed

T cell deficiency

DiGeorge syndrome

DiGeorge syndrome
The thymus dependent areas of lymph nodes and

spleen are depleted of the lymph nodes Circulating T cells are reduced in number Delayed hypersensitivity and graft rejection are depressed The humoral immune mechanism is largely unaffected

DiGeorge syndrome
The severity of the disease is dependent on the degree

of thymic hypoplasia

DiGeorge syndrome
Craniofacial features include Cleft palate Bifid uvula Oral candidiasis Microstomia Prominent forehead Short palpebral fissures

Defects in the MHC

Genes encoding for MHC is mutated
Lack adequate presentation of antigenic peptides to

CD8T cells leading to inadequate activation of cytotoxic T cells Opportunistic pathogens that infect oral cavity include
Candida albicans Herpes simplex viruses

B cell deficiency

Brutons X-linked Agammaglobulinemia

Patients with this disease have a profound defect in B

lymphocyte development resulting in severe hypogammaglobulinemia, an absence of circulating B cells, small to absent tonsils, and no palpable lymph nodes

Clinical manifestations
Most boys afflicted with XLA remain well during the

first 6-9 mo of life Thereafter, they acquire infections with extracellular pyogenic organisms

Streptococcus pneumoniae and Haemophilus influenzae

Normal response to viral infections

Diagnosis of XLA
All classes of immunoglobulins are grossly depleted in

the serum, Tonsils and adenoids are atrophic Lymph node biopsy reveals depletion of cells of bursa dependent areas Plasma cells and germinal centres are absent even after antigenic stimulation Decrease in proportion of B cell in circulation

Treatment of XLA
Initial administration of 300mg of gammaglobulin per

kg of body weight in three doses Followed by monthly injection of 100mg per kg body weight

Common variable immunodeficiency

characterized by hypogammaglobulinemia with

phenotypically normal B cells Late onset hypogammaglobulinemia It is characterised by recurrent pyogenic infection and increased incidence of autoimmune disease Malabsorbtion and giardiasis are common

Common variable immunodeficiency

The total immonoglobulin level is usually less than

300 mg per 100 ml IgG less than 250mg per 100 ml B cells may be present in circulation in normal numbers but they are defective in their inability to differentiate into plasma cells and secrete immunoglobulins Treatment is by administration of gammaglobulins

SELECTIVE Ig DEFICIENCY
An isolated absence or near absence (<10 mg/dL) of

serum and secretory IgA is the most common Pt with IgA deficiency has Increased susceptibility to respiratory infections IgM deficiency has been found to be associated with septicemia IgG deficiency is observed in relation to progressive bronchiectasis

HYPER IgM SYNDROME

In this group there is low IgA, and IgG level with

elevated IgM The IgM has normal structure and posses antibiotic activity Pt shows enhanced susceptibility to infections oral manifestations
Candidiasis

Midline defects of tongue

Delayed resorption and exfoliation of primary teeth

 multiple skin abscesses and coarse facial features

Facial features include greater inter-alar width, longer outer canthal distance prominent brows. Broad nasal bridge Prominent forehead

Cehdiak-higashi syndrome
Defective chemotaxis and defective intracellular killing

of bacteria can be observed clinical manifestations

partial oculocutaneous albinism associated with

photophobia and various neurological symptoms Hypopigmentation of skin and hair Neuropathy and ataxia Recurrent bacterial infection of skin And respiratory tract

Secondary immunodeficiency AIDS

Caused by HIV
Cells susceptible to HIV infection
CD4+T cells Monocytes and Macrophages Course of infection Mean latency period is 10 years Only 30% of HIV infected pt develop symptoms Persistent generalized lymphadenopathy

>3 months Collapse of immune system leads to numerous symptoms

Oral Disease in Patients with HIV Infection

Oral infections and neoplasms occur with

immunosuppression 90% of HIV + patients have at least one oral manifestation Oral disease is rarely self-limiting Untreated oral disease may lead to systemic infection, weight loss, dehydration, and malnutrition

Oral Manifestations of HIV/AIDS:

9 times higher prevalence when CD4+ T-cell count is

less than 200 cells/mm3 Microorganisms

Fungal Viral Bacterial

Neoplasms

 Fungal infections Candidiasis

Histoplasmosis Cryptococcosis

Viral infections Oral hairy leukoplakia Verruca vulgaris Herpes simplex virus Cytomegalo virus

Bacterial Infections

Actinomyces Enterobacter Mycobacterium (Tuberculosis

Neoplasm Kaposis sarcoma Lymphoma

Fungal
Pseudomembranous Candidiasis Opportunistic fungal infection caused most frequently by Candida albicans Primary locations include the tongue, buccal mucosa, hard and soft palate Considered asymtomatic; some may experience burning, pain, and altered taste Multi-focal, ill-defined, irregular white plaques that can be rubbed off

Pseudomembranous Candidiasis

Erythematous Candidiasis Opportunistic fungal infection caused most frequently by Candida albicans Primary locations include the tongue and hard palate Burning sensation and dry mouth Multi-focal, ill-defined, irregular red patches (median rhomboid glossitis)

Linear Gingival Erythema

Linear gingival erythema (LGE)- gingival disease of

fungal origin Diagnosis should be considered when plaque control, scaling and root planing fail to alleviate. Topical antimicrobial rinses such as 0.12% chlorhexidine may be helpful

 Angular cheilitis

Ulcerative, crusting lesions with erythema at the commissures. Multi-focal, hair-like projections on the cheek mucosa along the linea alba.

Hyperplastic candidiasis

When T count < 100 can develop into esophageal

candidiasis

Topical Treatment of Oral Candidiasis

Clotrimazole 10 mg troches dissolved in the mouth 5x

/day for 7-14 days Nystatin rinse, 100,000units/ml. Hold 1 tsp in mouth for 2 min and swallow or spit 4x/day Clotrimazole 1% cream- for angular cheilitis

Systemic Treatment of Oral Candidiasis

(consider when CD4 count is lower than 150)

Fluconazole 100 mg daily for 14 days

Ketoconazole 200 mg daily for 14 days

Viral Lesions
Oral Hairy Leukoplakia Epstein-Barr (EBV) virus Regarded as a marker of mmunosuppression Predictive of disease progression to AIDS Affects the lateral borders of the tongue, ventral tongue and buccal vestibule Usually asymptomatic Usually treatment not indicated

Oral warts Human papillomaviruses (HPV) Appears as smooth-surfaced, flesh-colored or white papules Oral verruca vulgaris is a papillary or pedunculated form of HPV Occur mostly on keratinized mucosa Treatment is excision when indicated On the rise- concern with HPV/CA link

Oral Herpes Simplex/ Herpes Labialis(fever blisters)

Herpes Simplex Virus (HSV) Generally more widespread, aggressive, prolonged,

and atypically distributed than in nonimmunosuppressed patients Typical sites include the hard palate and the attached gingiva but oral mucosal surfaces may be involved Appear as small vesicles that coalesce with weeping crusts or yellow border

 Lesions are painful and may interfere with nutrition

Treatment options

Acyclovir (Zovirax) 400-800 mg 3x/day for 7 days Valacyclovir 500 mg twice daily for 7 days Palliative support- mouthrinse

Topical acyclovir ointment for recurrent herpes

questionable effectiveness

Cytomegalovirus (CMV)
Painful, large, sharply demarcated, nonspecific

ulcerations, usually represented by dissemination of CMV Occurs on both keratinized and nonkeratinized mucosa and clinically cannot be distinguished from major aphthous ulcerations Diagnosis only rendered by deep biopsy CMV causes retinitis in AIDS patients Rx Ganciclovir, especially when retinitis

Periodontal Diseases
Most common oral bacterial infection among HIV

infected persons Contributing factors include poor diet, poor oral hygiene, and xerostomia Regular cleanings and good oral hygiene needed Greater prevalence with increased viral load and presence of Candida and herpesviruses Necrotizing periodontal diseases

Necrotizing ulcerative gingivitis (NUG) Necrotizing ulcerative periodontitis

 Necrotizing ulcerative gingivitis (NUG)

Characterized by ulceration and necrosis of the interproximal gingiva with mucosal sloughing Often responsible for rapid tissue destruction When extends into the adjacent tissues and bone

Necrotizing ulcerative periodontitis (NUP)

Necrotizing Periodontal Diseases

Treatment of NUG/NUP involves the use of aggressive

tissue debridement to remove pathogens and the administration of systemic antibiotics Povidone-iodine as irrigant during debridement Flagyl (metronidazole) 250 mg 3 x/day x 5days Amoxicillin 500mg with Flagyl 3X/day x 5days Antimicrobial rinses (0.12% Chlorhexidine)

Other Ulcerative Lesions

Recurrent Aphthous Stomatitis (canker sores)

Idiopathic problem that affects 40% of the general population

Occurs with increased frequency with HIV infection Minor are small ulcerations ( < 1 cm) Major are large ulcerations ( > 1 cm)

Recurrent Aphthous Stomatitis

Topical steroids such as dexamethasone 0.5mg/5ml-

swish 30 secs then spit 4x/day OTCs to cauterize or cover smaller lesions Systemic steroids in severe cases and major apthous prednisone 20mg 3X/day X4 days then reduce 5mg each day.

Kaposis Sarcoma (KS)

Most common malignancy associated with HIV
Human Herpesvirus 8 (HH-8) has been implicated as

a possible co-factor for KS Oral cavity may be the initial site in 50% of cases Early lesions appear as asymptomatic reddishpurple macules

 Lesions progress to painful papules and nodules that

may ulcerate and bleed Presence of KS always associated with immunodeficiency Also seen in kidney transplant recipients Treat with localized injection of
chemotherapeutic agents or surgical removal.

Non-Hodgkins lymphoma
second most common malignancy in AIDS
can be painful tumors present intraorally as soft tissue masses,

frequently with secondary ulcerations, and may resemble KS most commonly occurs on the palate, retromolar area, and gingiva