The document discusses immunologic disorders including primary immunodeficiencies like T-cell deficiencies, B-cell deficiencies, and complement deficiencies as well as secondary immunodeficiencies caused by drugs, infections, or other conditions. It describes common oral complications seen in specific immunodeficiencies such as oral candidiasis, recurrent herpes infections, and necrotizing gingival ulcerations. Guidelines are provided for managing dental procedures and risks in patients with immunodeficiencies or autoimmune disorders like systemic lupus erythematosus.

1. Immunologic Disorders
RESOURCE FACULTY
Dr. Jyotsna Rimal
Additional professor and HOD
Dr. Iccha kumar Maharjan
Associate professor
DEPARTMENT OF ORAL
MEDICINE AND RADIOLOGY PRESENTER
Nabin Chaudhary
BDS 2011

2. Contents
 Immunodeficiency
 Primary immunodeficiencies
Deficiencies in innate immunity:phagocyte deficiencies
Deficiencies in adaptive immunity
T-cell deficiencies
B-cell deficiencies
 Secondary immunodeficiencies
Innate immune system
 Autoimmune disease
SLE
Scleroderma

3. Immunity
Acquired(specific) Innate(natural)
active passive
Natural:
Follows clinical
or subclinical infection
Artificial:
Induced by vaccination Natural:
Transplacental
passage
of maternal IgG
Artificial:
Injection of
preformed
antibody(e.g ATS)
Birds immune to tetanus;
Algerian sheeps immune
to anthrax

4. INNATE IMMUNITY
Barriers
 Physical
 skin
 hair
 mucous
 Chemical
 sweat
 tears
 saliva
 stomach acid
 urine

5. Cells of innate immunity
Cells Location Function
Monocytes Blood Phagocytosis
Macrophages Tissue Phagocytosis, inflamation, Antigen
presentation
Neutrophils Blood Phagocytosis
Eosinophils Tissue/blood Cytolysis
Basophils Blood Inflammation
Mast cells Tissue Inflammation
Natural killer cells Blood/Tissue Cytolysis
Dendritic cells Tissue Antigen presentation

6. Adaptive immune response
 Third line of defense
 Precisely adapted to each specific microorganism encountered by an individual
 Memory
 Mounts rapid and efficient response in the next encounter
 Consists of
 Cells:
 B lymphocytes
 T lymphocytes
 Molecules:
 Antibodies,
 Cytokines
Primary:
Thymus
Bone marrow
Secondary:
Payer’s patch
Spleen
Lymph node
ORGANS

7. Antibody
Two light chains (κ or λ)
Two heavy chains (γ, α, μ,δ, ε)
V: variable segment
C: constant segment
IgG
Major defence against bacteria and their toxin

8. % of total
immuno-globulin
Functions
IgG 80 Complement activation, Major
defence against bacteria and their
toxin
IgA 13 Localized protection in external
secretions (tears, intestinal
secretions, etc)
IgM 6 Complement activation, Antigen
recognition by B cells
IgD 0.1 Antigen recognition by B cells
IgE 0.002 Major defence against helminths;
mediates allergic reation, releases
histamine from basophils and mast
cells

9. Immunity in Oral Cavity
Homeostasis in oral cavity is maintained by innate and acquired system
in conjunction with normal oral flora and an intact oral mucosa.
Components contributing for oral defence:
 Mucosal integrity
 Major and minor salivary gland saliva
 Salivary innate microbial proteins
 Gingival crevicular fluid
 Transudating plasma proteins
 Circulating white blood cells
 Oral mucosal keratinocyte
products
 Protein from microbial flora

10. IMMUNODEFICIES
PRIMARY
IMMUNODEFECIENCY(<10%)
• TCELL DEFECT
• B CELL DEFECT
• COMPLEMENT DEFECT
• PHAGOCYTIC DEFECT
SECONDARY
IMMUNODEFECIENCY(90%)
.DRUGS
.INFECTIONS
Congenital
Manifests since early age
Acquired
Manifests at any age
Result either from production or
destruction of immune cells or
loss of components of humoral immunity

11. Immunodeficiency
T-cell deficiencies B-cell deficiencies
 in T-cell number e.g.DiGeorge
Syndrome(Velocardiofacial
syndrome)
Qualitative T-cell defects
e.g.Defects in MHC
 in B-cell number e.g.Bruton’s X-linked
Agammaglobulinemia and Non Bruton’s
Agammaglobulinemia
 in certain classes of immunoglobulins e.g.
common variable immunodeficiency;
selective immunoblobulin deficiency
Severe combined immunodeficiency(SCID)
Wiskott Aldrich syndrome
Ataxia Telangiectasia

12. Oral complication with specific
immunodeficiencies
Immune defect Disease example Common
infectious
susceptibility
Oral complications
Severe in
neutrophil no.
Kostmann’s
syndrome,
Severe congenital
neutropenia
Bacterial and
Fungal infections
Aggressive periodontitis,
Recurrent oral ulcerations,
Delayed wound healing,
Candidiasis
Defective
chemotaxis of
neutrophils
Leukocyte
adhesion
deficiency
Bacterial and
Fungal infections
Aggressive periodontitis,
Recurrent oral ulcerations,
Delayed wound healing,
candidiasis

13. Unknown Job’s syndrome Recurrent skin and
mucous membrane
infections
Delayed exfoliation of
primary teeth,midline
defects of tongue,oral
candidiasis,characteristic
face with broad nasal bridge
Severely T-
and B-cell no.
SCID Infections of all
types
Oral candidiasis,herpes,
recurrent oral ulcerations,
severe necrotizing gingival
ulcerations
in T-cell no. DiGeorge
syndrome
Recurrent viral and
fungal infections
candidiasis,recurrent
herpetic infections

14. Abnormal T-cell
function
MHC class I deficiency
of CD8 T-cell
MHC class II deficiency
of CD4 T-cell
Recurrent viral
and fungal
infections
candidiasis,recurrent
herpetic infections
Severly B-cell
no.
Bruton’s X-linked
agammaglobulinemia
Recurrent
respiratory and
sinus infections
Possible sepsis from
odontogenic
infections
Solitary
immunoglobulin
class deficiency
Selective IgA deficiency
Selective IgG deficiency
Varied from no
symptoms to
recurrent
respiratory and
sinus infections
Candidiasis,oral
ulcerations,possible
sepsis from
odontogenic
infections

15. Severe combined immunodeficiency
 Immunocompromised;most die of infection before age of
1 year
 Types
1 adenosine deaminase deficiency
2 Mutation in Υc subunit of cytokine receptors
3 mutation in RAG1 or RAG2
4 mutation in CD3δ and CD3ε chains
 Treatment
Hematoietic stem cell transplantation(standard treatment)
Ex-vivo gene therapy
 Aphthous like ulcerations
 Candidiasis
 Herpetic infections
 Severe necrotizing gingival
ulceration
Oral complication

16. Wiskott Aldrich Syndrome
Prof Ariyanto Harsono MD PhD SpA(K) 16
Oral manifestations
 Purpura
 Candidiasis
 Herpetic
infections
Characterised by triad of symptoms
 Microthrombocytopenia
 Eczema
 Immunodeficiency
Defect in WAS gene,which affects both T and B cells as well as
platelets
C/F
Petechie
Bruising
Bloody diarrhea
Otitis media
Pneumonia
Skin infections

17. 17
 Ocular and facial telangictases
 Sinopulmonary infections
 impaired organ maturation
 x-ray hypersensitivity
 predisposition to malignancy.
Ataxia-Telangictasia
C/F
Mutation of ATM gene
Degenerative disorder characterized by cerebellar degeneration
Treatment
Intravenous pooled immunoglobulin

18. DiGeorge Syndrome
18
Craniofacial features:
Cleft palate
Bifid uvula
Oral candidiasis
Short palpebral fissures
Small mouth
Prominent forehead
Enamel hypoplasia
Anterior glottic webs
Result from deletion of chromosome
22q11.2;leading to failure of complete
development of thymus
Treatment
Thymic transplantation

19. X-linked agammaglobulinemia(bruton’s Disease)
Mutation in the gene called bruton thyroid kinase(BTK)
Virtual absence of B-cells
Very low level of all immunoglobulins( IgG, IgA, IgM, IgD and IgE)
Treatment
Aggressive antibiotic treatment and intravenous pooled
immunoglobulin transfusions

20. Secondary immunodeficiencies
 Cellular(primarily neutrophils)
 Neutropenia results during cancer chemotherapy, stem cell transplantation,aplastic
anemia and autoimmune neutropenia
 If ANC<1000cells/mm3 risk of nfection.Thus antibiotic prophylaxis should be given
prior to invasive dental procedures
 Complement
 Acquired deficiency seen in advanced liver disease
 Associted with increased incidence of bacterial infections and malignancies(CLL)
Innate immune system

21. Adaptive immune system
 Decrease in T-cell no eg HIV and/or function eg chronic GVH
disease,treatment with anti tumor necrosis(TNF-α)
Agents
 Infections with intracellular bacteria and fungi(pneumocystis
carinii),viruses(herpes family,papilloma virus) and parasites(Toxoplasma
and cryptosporidium) are typical of T-cell-deficient states
 Oral candidiasis(advanced HIV)
 Herpes zoster(CLL)
Homoral(antibodies)
• Associated with increased loss of immunoglobulin eg nephrotic syndrome
• And decreased production of immunoglobulin eg multiple myeloma, CLL
Cell mediated

22. Case study  Immunological investigations
 Quantitative serum immunoglobulins (g/L):
 IgG 0.17 (5.5–10.0)
 IgA Not detected (0.3–0.8)
 IgM 0.07 (0.4–1.8)
 Antibody activity
 Immunization responses – no detectable IgG antibodies to:
 Tetanus toxoid (post Imx)
 Haemophilus type b polysaccharides (post Imx)
 Polio (post Imx)
 Measles (post Imx)
 Rubella (post Imx)
 Isohaemagglutinins (IgM) not detected (blood group A Rh+)
 Blood lymphocyte subpopulations (×109/L):
 Total lymphocyte count 3.5 NR* (2.5–5.0)
 T lymphocytes (CD3) 3.02 NR (1.5–3.0)
 B lymphocytes (CD19) <0.1 NR (0.3–1.0)
Peter was born after an uneventful pregnancy.
 At 3 months, he developed otitis media
 At the ages of 5 months and 11 months, he was
admitted to hospital with untypable Haemophilus
influenzae pneumonia.
 He is the fourth child of unrelated parents;his
three sisters showed no predisposition to
infection.
 All immunizations were uneventful.
 severe reduction in all three classes of serum
immunoglobulins and no specific antibody
production
 mutation in the Btk gene was detected

23. Diagnosis???
 Bruton’s disease(X-linked agammaglobulinaemia)
 Treated by 2-weekly intravenous infusions of human
normal IgG in a dose of 400 mg/kg body weight/month.

24. McQ
 Which of the following Ig is involved in mediating allergic reactions
 a) IgG
 b) IgM
 c) IgE
 d) IgA
 All of the following are autoimmune disorders except
 a) Graves disease
 b) SCID
 c) Rheumatoid arthritis
 d) Addison’s disease
(b)
(c)

25. Systemic lupus erythematosus
Autoimmune disorder characterized by multisystem microvascular
inflammation with the generation of autoantibodies
When the skin is involved- lupus dermatitis or cutaneous lupus
erythematosus.
isolated to the skin, without internal disease- discoid lupus.
internal organs are involved-systemic lupus erythematosus (SLE)

26. Etiology and pathogenesis ____________________
Genetic Environmental
Though etiology is unknown
Progressive loss of tolerance
Production of autoantibodies

27. Manifestations
CVS
Lung
Kidney(Renal)
Musculoskeletal
CNS
others

28. American college of Rheumatology criteria
MALAR RASH
DISCOID RASH
PHOTOSENSITIVITY
ORAL ULCERS
ARTHRITIS
SEROSITIS
RENAL DISORDER
NEUROLOGIC DISORDER
HEMATOLOGICAL DISORDER
IMMUNOLOGIC DISORDER
ANTINUCLEAR ANTIBODY
If ≥4 of these criteria,are present diagnosis likely to
be SLE ;sensentivity=70-96%;specificity=90-100%

29. Antibody Prevalence(%) Clinical utility
Antinuclear antibodies 98 Best screening test; repeated negative tests make
SLE unlikely
Anti-dsDNA 50-60 Highly specific
Anti-Sm 25 Specific for SLE
Anti-RNP 40 Not specific for SLE
Anti-Ro (SS-A) 25-40 Not specific for SLE;associated with sjogren’s
Syndrome,linked to subacute cutaneous lupus and
neonatal attack
Anti-La (SS-B) 10-15 Not specific for SLE;associated with sjogren’s syndrome
Laboratory investigations

30. Antihistone 70 More frequent in drug-induced lupus than in SLE
Antiphospholipid 50
Three tests available— ELISA s for cardiolipin and 2G1,
sensitive prothrombin time (DRVVT); predisposes to
clotting, fetal loss, thrombocytopenia
Antierythrocyte 60 Measured as direct Coombs' test; a small proportion
develops overt hemolysis
Antiplatelet 30 Associated with thrombocytopenia but sensitivity and
specificity are not good; this is not a useful clinical test
Antineuronal (includes
anti-glutamate
receptor)
60 In some series a positive test in CSF correlates with active
CNS lupus
Antiribosomal P 20 correlates with
depression or psychosis due to CNS lupus

31.  Immunohistology:
Direct Immunofluorescence
Lupus band test:
-Deposition of IgG;IgM and C3 in a band
like pattern at the dermo-epidermal
junction.

32. Oral manifestations
 Site:buccal mucosa,lip,palate,gingiva
 Symptoms:complains of burning
Sensation,xerostomia,soreness of mouth
 Characteristically painless
 Whitish striae radiating from central erythematous area,giving so
called ‘brush border’
 Lip lesion: central atrophic & occasionally ulcerated area with small
white dots surrounded by keratinized border composed of small
radiating white striae.
 INTRA ORAL LESION: composed of a central depressed red
atrophic area surrounded by 2-4 mm elevated keratotic zone that
dissolve into a white line.

33. Dental Management
 Risk of infection:
• Complete blood count
• If ANC<1000 cells/mm3;elective oral surgical procedures with potential for bacteremia should be
delayed
• Antibiotic prophylaxis often recommended
 Risk of bleeding
 Platelet transfusions recommended in surgical patients with platelet count<50,000/mm3
 controlled by local measures such as pressure and application of hemostatic agents,
 platelet transfusion can be performed postoperatively if bleeding occurs despite local measures
 Oral surgical procedures are safe with INR=2-3.5 and do not require discontinuation of anticoagulants
 Adrenal suppression
 Any patients with supraphysiologic corticosteroids intake for 2 weeks or longer in 2years time is at risk of
adrenal suppression

34. Adrenal insufficiency:corticosteroid supplementation
Dental surgical procedures Previous systemic steroid use Current systemic steroid use
Minor oral surgery lasting <1 hr
with local anesthetic only
Consider supplementation with
25mg of hydrocortisone
equivalent before surgery;esp. if
patient is infected
Consider supplementation with
25mg of hydrocortisone
equivalent before surgery;esp. if
patient is infected.No need to
supplement if the patient is
taking over 50mg
hydrocortisone equivalent daily
Oral surgery with or without GA
lasting >1 hr
Major oral surgery with GA
lasting >1 hr and having
significant blood loss,such as
cancer or orthognathic surgery
50-100mg of hydrocortisone equivalent the day of surgery,with
continuation of the dose for an additional day on the amount of
blood loss,presence of infection and length of surgery
Usual daily dose before surgery and hydrocortisone equivalent of
5o mg hydrocortisone IV during surgey and every 8hr after initial
dose for upto 72hr

35. Treatment
Medications Dose
NSAIDS Doses toward upper limit of recommended
range
Topical glucocorticoids 0.05%betamethasone dipropionate bd local
application x 2weeks followed by 2weeks
rest period
Topical sunscreens SPF 15 at least;30+preferred
hydroxychloroquine 200-400 mg/day
DHEA(dehydroepiandrosterone) 200mg/day
Methotrexate b(for dermatitis,arthritis) 10-25 mg once a week,po or sc with folic
acid;decrease dose if CrCl<60mL/min

36. Glucocorticoids oral Prednisolone:
0.5-1 mg/kg per day for severe SLE
0.07-0.3 mg/kg per day or qod for mild
SLE
Methylprednisolone sodium succinate iv For severe dz;1g iv/day x 3days
cyclophosphamide IV 7-25 mg/kg /month x 6month;consider
mesna administration with dose;
1.5-3 mg/kg per day(decrease dose for
CrCl<25ml/min)
Mycophenolate mofetil 2-3g/d PO(decrease dose if
CrCl<25mL/min)
Azathioprine 2-3mg/kg per day PO(decrease frequency
of dose if CrCl<50mL/min)

37. Scleroderma
 Chronic disease characterised by
- thickening and fibrosis of skin
 Systemic sclerosis:fibrosis extends to internal organs
including heart,lungs,kidney,and GI tract
 Types
A) localized form
i) linear
ii) morphea
B) progressive systemic sclerosis
i) limited cutaneous scleroderma
ii) diffuse cutaneous scleroderma
En coup de sabre
Morphea

38. Etiology and pathogenesis
 Etiology is unclear
 Genetic predisposition
 Environmental exposure to pesticides,benzene derivatives,silica
 Viral triggers such as parvovirus B19
 Pathogenesis is characterized by vascular damage
 Unregulated collagen deposition is a hallmark of disease

39. Clinical features
 Raynaud’s phenomenon
 Cutaneous manifestations
 Musculoskeletal manifestations
 GI manifestations
 Cardiac manifestations
 Pulmonary manifestations
 Renal manifestations
Lab investigations
• ANA(>90%patients)
• Anticentromere(ACA)
• AntitopoisomeraseI(Anti topo I)
• Anti RNA polymerase I/III
• Anti Th/To2-36

41. Oral manifestations
 Difficulty in opening mouth and loss of
tongue movement due to perioral and
lingual fibrosis
 Lips become thin, rigid & fixed
producing microstomia
 Maxillary anterior teeth are exposed
due to retraction of lips
 Masklike appearace to face
 Tongue becomes hard and rigid
causing difficulty in speaking and
swallowing.

42.  Reduce salivary flow rate(due to medications)
 Gingival hyperplasia(due to CCB)
 Loss of taste, pemphigus,bood dyscrasias
lichenoid reaction(due to penicillamine)
 Classic radiographic finding is generalized
uniform widening of periodontal ligament
space(2-4 times)
 Bone resorption at the angle of
mandible,condylar heads,coronoid process or
digastric region(when fibrosis involves muscles of
mastication)

43. Dental aspect
 Physical limitation caused by narrowing of oral aperture and rigidity
of tongue
 Poor oral hygiene;caries and plaque associated with decreasing
dexterity
 Dental procedures(molar endodontics,prosthetics,restoration in
posterior regions)become difficult
 Dental treatment altered due to physical problem of access
 Mouth stretch exercises
 No. of tongue blades increased between posterior teeth to stretch
facial muscles
 B/L commissurotomy

44. management
 Non-pharmacological:
- Take warm water bath
- Avoid cold contact ( Especially in winters)
- Wear woolen gloves and socks
- Smoking and drugs like B-blocker inducing vasospasm
is strictly prohibited

45. Pharmacological
 CCB, Nifedipine(30-90mg/day), non responsive once can use
Nicardipine(30-60mgbid)
 Combination of Pentoxifylline(400mg bid) and low dose aspirin(75 mg/day).
Pentoxifylline improves digital perfusion by increasing the deformability of RBC
plasma membrane
 Immunomodulators: cyclosporine, methotrexate.
 Antifibrotic therapy: D-PENICILLAMINE(start with 125-250mg OD then 250mg BD)
INFά & INFγ.

46. Case study
A 26-year-old woman presented
with fatigue and painful, stiff
knees of 4 weeks’ duration.
 She had a 6-year history of
raynaud’s phenomenon,
frequent mouth ulcers and
had had a blotchy rash
 Bilateral effusions in both
knee joints, but all other
joints were normal.
 She had no skin lesions,
muscle tenderness,
proteinuria or fever.
 Full blood count showed mild
thrombocytopenia and
lymphopenia
Investigations
C-reactive protein 8 mg/l (normal)
Rheumatoid factor Negative
Antinuclear antibody Positive
Anti dsDNA-antibodies 80 (<25)
Serum complement levels
C3 0.35 g/l (NR 0.65–1.30)
C4 0.05 g/l (NR 0.20–0.50)
Serum immunoglobulins
IgG 22.0 g/l (NR 7.2–19.0)
IgA 3.8 g/l (NR 2.0–5.0)
IgM1.2 g/l (NR 0.5–2.0)
Biopsy of normal, sun-exposed skin (lupus band
test) Granular deposits of IgG and complement
at dermo–epidermal junction
Lupus band test
Well-demarcated digital ischaemia due to Raynaud’s phenomenon
Blotchy erythema on the dorsum of the hands

47. Diagnosis???
 SLE
 treated with aspirin for her painful knees
 Following treatment with hydroxychloroquine, the skin
manifestations gradually disappeared

48. Revision
 American college of rheumatology criteria for SLE
 Corticosteroids supplementation
 Most sensitive diagnostic test for SLE=
 CREST syndrome
 Most common problem associated with scleroderma for
dental procedures=
 Longest life which immunoglobulin=
 Immunoglobulin in secretions=
ANA
Trismus
IgG
IgA

49. McQ
 In severe combined immune deficiency (SCID), the patients are
deficient in
a) B cells
b) T cells
c) both a and b
d) IgA
 SCID can occur due to the absence of an enzyme
a) adenosine deaminase
b) guanosine deaminase
c) phosphorylase
d) thymidine deaminase
(c)
(a)

50.  All of the following are immunodeficiency diseases except
a) Graves disease
b) SCID
c) DiGeorge’s syndrome
d) Hyper IgE syndrome
 Some defects or mutations in components of innate or
adaptive immunity may lead to
a) hypersensitivity
b) auto-immune diseases
c) immunodeficiency
d) tolerance
(c)
(a)

51. References
 Burkit’s Oral Medicine 11th edition
 Textbook of oral medicine,2nd edition,Anil Ghom
 A textbook of microbiology p. Chakraborty
 Understanding medical physiology RL Bijlani 4th edition
 McGraw-Hill’s access medicine
 Essentials of Clinical Immunology, Sixth Edition. Helen Chapel, Mansel Haeney, Siraj
Misbah, and Neil Snowden.© 2014 John Wiley & Sons, Ltd. Published 2014 by John
Wiley & Sons, Ltd.
 Google