Causes for primary immunodeficiencies
· X linked agammaglobulinaemia
§ X linked hypogammaglobulinaemia
§ Immunoglobulin deficiency with increased IgM
§ Immunoglobulin heavy chain gene deletion
§ Kappa chain deficiency
§ Common variable immunodeficiency
§ IgA deficiency
§ Transient hypogammaglobulinaemia of infancy
§ Selective IgG subclass deficiency
· Combined immunodeficiency
§ Severe combined immunodeficiency
§ Adenosine deaminase deficiency
§ Purine nucleoside deficiency
§ Major histocompatibility complex (MHC)ii deficiency
§ Reticular disgenesis
· Well defined immunodeficiency syndromes
§ Wiskott-aldrich syndrome
§ Ataxia telengiectasia
· Other syndromes associated with immunodeficiency
§ Bloom syndrome
§ Fanconi anaemia
§ Down’s syndrome
· Multiple organ system abnormalities
§ Partial albinism
§ Short limb dwarfism
§ Cartilage hair hypoplasia
§ Chediak –Higashi syndrome
· Hereditary metabolic defects
§ Transcobalamine 2 deficiency
§ Acrodermatitis enteropathica
§ Biotin dependent carboxilase deficiency
· Hypercatabolism of immunoglobulin
§ Familial hypercatabolism of immunoglobulin
§ Intestinal lymphangiectasis
§ Hyper IgE syndrome
§ Chronic mucocutaneous candidosis
§ Epstein-Barr virus associated immunodeficiency
· Defects in phagocytic function and neutropenia
§ Chronic granulomatous diseases
§ Neutrophil G6PD deficiency
§ Myeloperoxidase deficiency
§ Lecocyte adhesion defects
§ compliment deficiency
Secondary Immunodeficiency Conditions
§ Acute severe viral infections
· Drug induced
§ Immunosuppressive drugs
§ Cytotoxic drugs
· Myeloproliferative disordes
§ Hodgkin’s and non Hodgkin’s lymphomas
· Metabolic disorders
§ Iron deficiency
§ Diabetes mellitus
· Autoimmune diseases
§ Sickle cell disease
§ Chronic renal failure
§ Severe burns
Primary immunodeficiency disorders and their related oral diseases
Severe combined immunodeficiency
This disease consists of profound deficiency of cell mediated and humoral immune systems. Oral conditions associated are candidal infections and recurrent oral ulcerations.
Common variable immunodeficiency
Failure in B differentiation and defective are the main features of this condition. Aphthous like ulceration, enamel hypoplasia and pseudomembranous candidosis are the possible oral complications.
Selective IgA deficiency
There is failure of terminal differentiation of IgA producing B-cells resulting in recurrent sinusitis and increased risk of oral infections. Tonsilar and adenoidal hypoplasia may also present.
Wiskott - Aldrich syndrome
This syndrome causes cell membrane defects affecting haemopoietic stem cell derivatives. Related oral conditions are herpetic and candidal infections, spontaneous gingival bleeding, perpura petechiae, and mucosal ulcers.
Chromosomal abnormality leading to reduced T-cells. Oral manifestations are severe ulcers, palatal non-Hodgkin’s lymphomas, palatal telengiectesia and facial hypotonia.
Di George syndrome
Main feature of this syndrome is embriopathy of thymic development. Related oral conditions are severe mucocutaneous cadidosis and enamel hypoplasia. Other clinical manifestations are prominent forhead, short philtrum and hypertelorism.
Main immunological impact is on phagocytic cells. Related oral diseases are ANUG and early severe periodontitis. Delayed eruption of teeth also possible,
Chediac Higashi syndrome
Cause phagosome lysosome adhesion abnormalities. Oral ulceration, severe periodontits and lymphadenopathy could be seen.
Neutrophil deficiency causes reduced immunity. Oral manifestations are recurrent oral ulcers on lips, tongue and buccal mucosa gingivitis and enamel hypoplasia. In cyclic neutropenea oral lesions may also appear cyclically.
Chronic granulomatous disease of childhood
Cause abnormal production of superoxide free radicals. Oral lesions are severe gingivitis and periodontitis, eczematous lesions in the face and lips, invariable lymph node enlargement.
`Leukocyte adhesion defects
Defects in mobility, chemotaxis, adhesion and endocytosis are present. In these patients recurrent bacterial infection of the mucosa and skin could be present. Gingivitis occur as soon as the primary teeth erupt.
Neutrophil G6PD deficiency
Recurrent infections are common in these kind of patients.
Hereditary myeloperoxidase deficiency
Recurrent infections and candidosis are common.
Secondary (acquired) immunodeficiency disorders and their related oral diseases
Drug induced immunodeficiency
Nowadays immunosuppressive drugs are used more frequently and extensively in medical practice (E.g. renal transplant, organ transplant, management of immune mediated diseases). Commonly used immunosuppressants include corticosteroids, such as prednisone and prednisolone, cytotoxic drugs, such as azathioprine, chlorambucil, cyclophosphamide, and methotrexate, and others such as antilymphocyte immunoglobulin and cyclosporine.
The most common complication is infection. In times infection can be fatal. Fungal and viral infections particularly candidal are the common oral conditions.
This is one modality of cancer treatment which causes immunodeficiency as a side effect. Myalosuppresion is the main effect. Oral complications are xerostomia and ulcerations. According to the site treated, late effects reflect both the loss of slowly proliferating and local endarteritis which produces ischemia to the related site leading to increased susceptibility to infections. Osteoradionecrosis is one such complication following radiotherapy for oral cancer.
HIV can be presented with variety of oral manifestations and oral diseases which sometimes first sign to be present. HIV is a retro virus which responsible for acquired immunodeficiency syndrome (AIDS). It attacks mainly CD4 cells. There is a progressive and profound reduction of CD8 cells and CD8 cells as well. Virus can attack monocytes, macrophages, dendritic cells and B cells also. This will result in reduced immunity of the patient. Oral disease related with AIDS can be classified into three groups
· Lesions strongly associated with HIV infections
· Lesions less commonly associated with HIV
· Lesions rarely associated with HIV
Group 1 – lesions (strongly associated with HIV)
v Candidosis – pseudomembraneous (most common)
v Hairy leukoplakia
v Kaposi’s sarcoma
v Non Hodgkin’s lymphoma
v Linear gingival erythema
v Necrotizing gingivitis
v Necrotizing periodontitis
Group 2 – lesions(less commonly associated)
v Bacterial infections - Mycobacterium intercellularae
v Viral infections – Herpes simplex
Human papilloma virus
Varicella zoster virus
v Salivary gland diseases – Xerostomia
Major gland diseases
v Miscellaneous – Melanotic pigmentation
Group 3 – lesions (rarely associated)
v Bacterial infections – A. Isrelii
v Viral infections – Klesiella pneumonia
CMV, Molluscum contagiosum
v Fungal infections – Cryptococcus neofomnas
v Neurological diseases – Facial palsy
v Due to drug therapy of AIDS - Ulcers, Erythema multiforme, Lichenoid reactions, Toxic epidermolysis, SCCA
Myeloma, leukaemias are the common disorders which result in reduction in immunity and give rise to oral symptoms.
This is a relatively rare disease with an incidence of about 10 per 100000 per year. Leukaemia classified as being acute or chronic and myeloid or lymphoid origin. More than ½ of patients present acutely. General classification is as follows.
o AML – Acute myeloid leukaemia
o ALL – Acute lymphoblastic leukaemia
o CML – Chronic lymphoblastic leukaemia
The disease has unknown aetiology but several factors such as radiation, chemicals, drugs, genetics, viruses, have been associated. The effect of leukemic overproduction of white cells is to suppress other cell lines of the marrow leading to immunodeficiency. Impairment of normal haemopoisesis resulting anaemia, granulocytopenia and thrombocytopenia and patient is having attenuated immunity. Oral effects of acute leukaemia are
§ Gingival swelling
§ Mucosal ulceration
§ Leukaemic deposits
o Acute myalocytic leukaemia –
§ Grossly swollen gingivae
§ Ulceration in palatal aspect of anterior teeth
Lymphomas are more common than leukaemias. Result in abnormal proliferation of lymphoid system. Hence can occur in any site where lymphoid tissue is found. According to the histopathological appearance can be classified into
v Hodgkin’s lymphoma – hall mark is Reed-Sternberg cell derived from germinal centre B-cell or rarely peripheral T-cell. Accounts for 25% of malignant lymphomas. Lymph node enlargement most often in cervical region. They are usually painless and rubbery in consistency.
v Non- Hodgkin’s lymphoma- more common and comprise rest of cases. Adults are predominantly affected. Lymphomas present inside the oral cavity usually soft, painless swellings which way become ulcerated by trauma. Infection is also common.
Neoplastic proliferations of lymphopoietic portion of reticulo endothelial system result in attenuated immunity
Conditions such as malnutrition, iron deficiency result in redused cell s mediated immunity. Diabetes mellitus is the other important and common condition which has oral complications due to reduced immunity.
One of the most common endocrine disorder that occur due to deficiency of insulin or due to impairment of insulin function which result in high blood sugar levels. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).
There are three main types of diabetes:
· Type 1 diabetes: results from the body's failure to produce insulin, and presently requires the person to inject insulin. (Also referred to as insulin-dependent diabetes mellitus, IDDM for short, and juvenile diabetes.)
· Type2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. (Formerly referred to as non-insulin-dependent diabetes mellitus, NIDDM for short, and adult-onset diabetes.)
· Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.
Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.
In DM defective phagocytosis is proboly the main cause for reduced immunity. The associated oral diseases are
· Susceptible for infections (candidosis)
· Complications due to Xerostomia (due to polyuria and dehydration)
· Periodontal disease (exaggerated response to plaque)
· Lichenoid reactions due to antidiabetic drugs
Chronic autoimmune hepatitis, SLE like diseases are autoimmune disease related with T- cell defects. These patients have increased risk for oral infections.
Systemic lupus erythematosus
SLE is inflammatory multisystem disorder with arthralgia and rashes as the most common clinical features. This condition is 9 times more common in women than in men with a peak age of onset between 20-40 years. Loss of self tolerance has several consequences there is impaired T-cell regulation on immune system leading to immune deficiency. Oral manifestation is oral ulceration.
Neutropenia is defined as circulatory neutrophil count below 1.5 ×109 /L. Acquired causes may be viral infections, severe bacterial infections, immune nurtopenia (autoimmune neonatal netropenia) inherited causes are ethnic (common in black races), cyclic neutropenia(genetic defect with neutropenia every 2-3 weeks)
Frequent infections, often serious, characteristic glazed mucositis and oral ulcerations are common.
Is a multisystemic disorder of unknown aetiology characterised by non-caseating granulomas in many tissues and organs. It is commonly affects young adults and usually presenting with bilateral hilar lymphadenopathy, pulmonary infiltration and skin or eye lesions. There is depresses cell mediated reactivity and overall lymphopenia. Circulating T lymphocytes are low but B cells are slightly raised.
Lip swelling, gingival and palatal nodules can occur. Unilateral or bilateral parotitis with painful enlargement occur in less than 10% of patients and some go on to develop xerostomia. Combined uveoparotid involvement is described as Mikulicz syndrome.
Sickle cell disease is an autosomal dominant condition. Hb S result from a single base mutation of adenine to thymine which produces a substitution of valine for glutamate at sixth cordon of the β globulin chain. Sickling off cell under low O2 concentration , resulting a short red cell survival. Ther is increased blood viscosity and reduced blood flow result in thrombosis and infarction with chronic haemostasis. There is reduced immunity and low Hb levels. Infections are common in tissues susceptible to vaso occlusion.
E.g. bones, lungs, kidney
Oral manifestations are
· Pallor of mucosa with jaundice
· Delayed eruption
· More prone to osteomyalitis
· Parasthesia of mental nerve
· Bimaxillary proclination , high cheek bones
Some of the important immunodeficiency conditions which were discussed above with related oral disease conditions are important in several ways for the dental practitioner. Early diagnosis, appropriate referrals and management of oral complications of these conditions are the important duties that dental practitioner must deal with.