Immune Deficiency and Oral Diseases
Immunity
The protection against infectious
disease conferred either by the immune response generated by immunization or
previous infection or by other nonimmunologic factors.
·
Immune system consist of 2
components
1. Non specific immunity
2. Specific immunity
·
Cell mediated
·
Humoral
Immunodeficiency
Immunodeficiency
disorders are a group of disorders in which part of the immune system is
missing or defective. Therefore, the body's ability to fight infections is
impaired. As a result, the person with an immunodeficiency disorder will have
frequent infections that are generally more severe and last longer than usual.
Symptoms
The symptoms vary with the specific disorder.
Signs
- Persistent, recurrent infections
- Severe infection by microorganisms that do not usually
cause severe infection
other signs include:
- Poor response to treatment for infections
- Delayed or incomplete recovery from illness
- Certain types of cancers (such as Kaposi's sarcoma or
non-Hodgkin's lymphoma)
- Certain infections (including some forms of pneumonia
or recurrent yeast infections)
Tests used to help diagnose an immunodeficiency disorder may include:
·
Complement levels in the blood, or other tests to
measure substances released by the immune system
·
Immunoglobulin levels in the blood
·
Protein electrophoresis (blood or urine)
·
T (thymus derived) lymphocyte count
·
White blood cell count
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
·
Other
§ 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
·
Infections
§ HIV
§ Acute severe viral infections
·
Drug induced
§ Immunosuppressive drugs
§ Cytotoxic drugs
§ Radiotherapy
·
Myeloproliferative
disordes
§ Myeloma
§ Leukaemias
§ Hodgkin’s and non Hodgkin’s lymphomas
·
Metabolic disorders
§ Malnutrition
§ Iron deficiency
§ Diabetes mellitus
·
Autoimmune diseases
·
miscellaneous
§ Neutropenia
§ Sarcoidosis
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.
Ataxia telengectasia
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.
Down’s
syndrome
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.
Neurtopenia
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 occurs as soon as the primary teeth erupt.
Neutrophil
G6PD deficiency
Recurrent infections are common in this kind of patient.
Hereditary myeloperoxidase
deficiency
Recurrent
infections and candidosis are common.
Secondary
(acquired) immunodeficiency disorders and their related oral diseases
Drug induced
immunodeficiency
Immunosuppressive Drugs
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.
Radiotherapy
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.
Infections
HIV infection
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)
Erythematous
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
Mycobacterium
tuberculosis
v
Viral infections – Herpes
simplex
Human papilloma virus
Varicella zoster virus
v
Salivary gland diseases – Xerostomia
Major
gland diseases
v
Miscellaneous –
Melanotic pigmentation Thrombocytopenic purpura
Necrotising stomatitis
Group 3 – lesions (rarely associated)
v
Bacterial infections – A.
Isrelii
E-
Coli
v
Viral infections – Klesiella
pneumonia
CMV, Molluscum contagiosum
v
Fungal infections – Cryptococcus
neofomnas
Mucormycosis
Zygomycosus
Aspergillosis
v
Neurological diseases – Facial palsy
Trigeminal neuralgia
v
Due to drug therapy of AIDS - Ulcers, Erythema multiforme, Lichenoid
reactions, Toxic epidermolysis, SCCA
Myaloproliferative Disorders
Myeloma, leukaemias are the common disorders which
result in reduction in immunity and give rise to oral symptoms.
Leukaemia
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
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
Metabolic Disorders
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.
Diabetes
mellitus
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)
·
Sialadinosis
·
Complications due to Xerostomia (due to polyuria and
dehydration)
·
Periodontal disease (exaggerated response to plaque)
·
Lichenoid reactions due to antidiabetic drugs
Autoimmune diseases
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.
Miscellaneous Causes
Neutropenia
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)
Clinical features
Frequent
infections, often serious, characteristic glazed mucositis and oral ulcerations
are common.
Sarcoidosis
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 occurs in less than 10% of patients and some go on to
develop xerostomia. Combined uveoparotid involvement is described as Mikulicz
syndrome.
Sickle cell disease
Sickle cell disease
is an autosomal dominant condition. Hb S results 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.