OROFACIAL

GRANULOMATOSIS
(OFG) & SARCOIDOSIS
D R T M T L A D I N YA N E
 CONTENTS
1. Types of Granulomas
i. Foreign body granuloma
ii. Immune Granuloma
2. Type IV hypersensitivity reactions in the mouth
i. Lichenoid reaction to amalgam
ii. Chronic mucosal drug reaction
3. Infectious diseases associated with Granulomas
i. Oral tuberculosis
4. Systemic diseases associated with granulomas
i. Crohn’s disease
ii. Sarcoidosis
iii. Orofacial granulomatosis

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 GRANULOMATOUS INFLAMMATION
•Granulomatous inflammation is a form of chronic inflammation characterised by collections of
activated macrophages often with T lymphocytes , and sometimes associated with central
necrosis.
•Granuloma formation is a cellular attempt to contain an offending agent that is difficult to
eradicate .
•In this attempt there is often strong activation of T lymphocytes leading to macrophage
activation which can cause injury to normal tissue.
•The activated macrophages may develop abundant cytoplasm and begin to resemble epithelial
cells and are called epithelioid cells
•Some activated macrophages may fuse forming multinucleate giant cells

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 2 TYPES OF GRANULOMAS
•They differ in their pathogenesis.
•Foreign body granulomas are incited by relatively inert foreign bodies, in the
absence of T cell-mediated immune responses.
• Typically, foreign body granulomas form around materials such as talc
(associated with intravenous drug abuse) , sutures, or other fibre's that are
large enough to preclude phagocytosis by a macrophage and do not incite any
specific inflammatory or immune response.
• Epithelioid cells and giant cells are apposed to the surface of the foreign
body. The foreign material can usually be identified in the centre of the
granuloma, particularly if viewed with polarized light, in which it appears
refractile.

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 2 TYPES OF GRANULOMAS CONTINUED
•Immune Granulomas are caused by a variety of agents that are capable of
inducing a persistent T cell-mediated immune response.
• This type of immune response produces granulomas usually when the inciting
agent is difficult to eradicate such as a persistent microbe or a self antigen
• Macrophages activate T cells to produce cytokines such as IL-2, which
activates other T cells , perpetuating the response and IFN-ϒ which activates
the macrophages.
• Activated macrophages transform into epithelioid cells and multinucleate
giant cells called granuloma.

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 Type IV Hypersensitivity reactions in the
mouth (Aetiology)
•Primary aetiologies of orofacial granulomas include:
• foreign material including amalgam, cosmetic fillers, and suture material.
• Delayed hypersensitivity to flavouring agents and ingredients in oral hygiene
products and dental restorations have been associated with granulomas

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 Type 4 Hypersensitivity reactions
(Mechanism)
•The cell-mediated type of hypersensitivity is caused by inflammation resulting
from cytokines produced by CD4+ T cells and cell killing by CD8+ T cells.
•CD4+ T cell-mediated hypersensitivity induced by environmental and self
antigens is the cause of many chronic inflammatory diseases, including
autoimmune diseases
•In CD4+ T cell-mediated hypersensitivity reactions, cytokines produced by the T
cells induce inflammation that may be chronic and destructive.

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 TYPE 4 HYPERSENSITIVITY REACTIONS
(MECHANISM)
•The prototype of T cell-mediated inflammation is delayed-type hypersensitivity
(DTH).
•(DTH) is a tissue reaction to antigens given to immune individuals.
•In this reaction, an antigen administered into the skin of a previously immunized
individual results in a detectable cutaneous reaction within 24 to 48 hours
(hence
• the term delayed, in contrast to immediate hypersensitivity

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MECHANISMS OF T CELL MEDIATED IMMUNE
REACTIONS

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MECHANISMS OF T CELL MEDIATED IMMUNE REACTIONS

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GRANULOMATOUS INFLAMMATION
• A section of a lymph node shows several
granulomas, each made up of an aggregate of
epithelioid cells and surrounded by lymphocytes.
• The granuloma in the centre shows several
multinucleate giant cells.
• The events that give rise to the formation of
granulomas in type IV hypersensitivity reactions,
illustrating the role of TH 1

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LICHENOID REACTION TO AMALGAM

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CHRONIC MUCOSAL DRUG REACTIONS

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CONTACT STOMATITIS TO CINNAMON
ALDEHYDE

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Treatment
Reactions to dietary components should be sought and possible provoking substances avoided
Elimination diets may be warranted and many patients respond.

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Oral Tuberculosis
•Tuberculosis is the prototype of a granulomatous disease caused by infection
and should always be excluded as the cause when granulomas are identified. In
this disease the granuloma is referred to as a tubercle. (clinical manifestations
and management as in HIV oral lesions)

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 ORAL TUBERCULOSIS
•With certain persistent or nondegradable antigens, such as tubercle bacilli
colonizing the lungs or other tissues, the infiltrate is dominated by macrophages
over a period of 2 or 3 weeks. With sustained activation, macrophages often
undergo a morphologic transformation into epithelioid cells.
• Large epithelium-like cells with abundant cytoplasm. A microscopic aggregation
of epithelioid cells, usually surrounded by a collar of lymphocytes, is referred to
as a granuloma.
•This pattern of inflammation, called granulomatous inflammation

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 OROFACIAL GRANULOMATOSIS
•The term orofacial granulomatosis(OFG) was introduced by Wiesenfeld et. al in
1985 to describe a variety of clinical presentations that on biopsy show non-
necrotising granulomatous inflammation.

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 OROFACIAL GRANULOMATOSIS
•OFG refers to orofacial swellings created by granulomatous inflammation in the
absence of a previously diagnosed local or systemic disease ( Neville et al, 2019).
•The disorder should not be considered a final diagnosis but potential sign of an
underlying and not yet discovered from an adverse reaction to various
• foods or additives which include cinnamon, benzoates,
• butylated hydroxyinosole or dodecyl gallate (in
•menthol or in peppermint oil).
•A delayed type of hypersensitivity reaction appears to be involved, although the
exact antigen inducing the immunological reaction appears to vary in individual
patients.

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Orofacial
Granulomatosis
The most common clinical
presentation is painless swelling
which may be asymmetrical and
involve one or both lips
Initially the lips are soft and
doughy
Become firm, indurated and
persists with recurrence
Isolated lip involvement is
termed granulomatous cheilitis

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Orofacial
Granulomatosis
When enlarged lips are seen
with facial paralysis and
fissured tongue the triad has
been termed Melkersson-
Rosenthal syndrome

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 OROFACIAL GRANULOMATOSIS
•Orofacial granulomatosis also may be associated with gingival enlargement,
cobblestone buccal mucosa, and vestibular linear hyperplastic folds, often with
associated ulceration.
•Primary therapy should be directed at discovering and appropriately managing
any underlying associated disorder.
•If thorough local and systemic evaluations fail to identify an underlying
causation, intralesional triamsolone injections or systemic corticosteroids may
be administered

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OROFACIAL GRANULOMATOSIS

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OROFACIAL GRANULOMATOSIS

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 CROHN’S DISEASE
•Crohn Disease (CD) is a chronic idiopathic inflammatory disease that can involve
any portion of the alimentary tract characterized by discontinuous skip lesions
which occur from the mouth to the anus. The exact aetiology of CD is unknown
but studies link alterations in gut microbiome, defects in intestinal epithelial
barrier function and genetics.
•Oral involvement of CD has been reported in up to 80% of paediatric patients
with gastrointestinal diseases. In some studies more than 30-60 % of patient’s
oral manifestations precedes gastrointestinal involvement.

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 CROHN’S DISEASE
•The clinical features include intermittent swelling of the lips, swelling and
erythema of the gingiva, and linear ulceration with hyperplastic margins often in
the vestibules
•Cobblestoning of the buccal mucosa and mucosal tags are often present. Patient
symptoms range from complaints of tenderness on palpation to chronic pain.
Other oral manifestations included ulcers, gingival swelling, and cobblestoning

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CROHN’S DISEASE

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Management of crohn’s disease
•Management is to treat recalcitrant lesions medically.
•Conservative management usually includes topical corticosteroids, intralesional corticosteroid
injections (such as low-volume, high-concentrate, extended-release triamcinolone) or topical
tacrolimus.
• Oral clofazimine 100–200 mg daily for 3–6 months (hyperpigmentation and raised liver enzymes
are adverse effects) may be helpful.
•Other therapies include NSAIDs, sulfasalazine, antibiotics such as metronidazole, antimalarials
such as hydroxychloroquine, mast cell stabilizers, or low-dose methotrexate.
•Rarely, cheiloplasty is indicated.

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Oral sarcoidosis
Systemic disease that is characterised by
non caseating granulomatous inflammation

The disorder is known to be idiopathic

Abnormal immune response to infectious or

environmental agents in genetically
predisposed individuals

The most commonly affected anatomic sites

are the lungs, skin, lymph nodes and eyes

Oral manifestations are uncommon and if

present may lead to the initial diagnosis

Any mucosal site may be affected,

presenting as brownish-red, or normal
coloured macule, papule or submucosal
mass.

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Oral manifestation of Sarcoidosis
Any oral mucosal site can be affected.
Most often appearing as a submucosal mass, isolated papule an area of
granularity or ulceration.
The mucosal lesions may be normal in colour, brown red or hyperkeratotic.
Most commonly affected sites
Buccal mucosa, followed by the gingiva, lips, tongue and palate.
Other orofacial sites that are commonly affected by sarcoidosis includes, lymph
nodes and salivary glands

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Oral sarcoidosis
Intraosseous lesions may be seen and
present as ill defined radiolucency that
may be associated with loosening of
teeth.

Majority of oral sarcoidosis cases resolve

spontaneously

Severe progressive cases are treated with

corticosteroids

Corticosteroids are first line of therapy

Followed by other immunosuppressive

medications or antimalarial

Oral mucosal lesions can be excised

surgically when localised

Osseous lesions should receive enough 31

curettage
Disease Cause Tissue reaction
Type 4 hypersensitivity in the mouth Food( Dairy, Eggs, Nuts) Food Variable depending on the causative
additives(benzoic acid, cinnamon agent and individual immune reaction
Foreign bodies
Oral Tuberculosis Mycobacterium Caseating granuloma (tubercle):
tuberculosis tuberculosis focus of activated
macrophages
(epithelioid cells), rimmed by
fibroblasts, lymphocytes,
histiocytes, occasional Langhans
giant cells; central necrosis with
amorphous granular debris;
acid-fast bacilli

Crohn’s Disease Immune reaction against intestinal Occasional noncaseating

bacteria possibly self antigens granulomas in the wall of the
bowel intestinal intestine, with dense
chronic inflammatory infiltrate

Sarcoidosis Unknown aetiology Granulomas of sarcoidosis show a

collection of epithelioid
histiocytes, along with multinucleated
cells. Typically sarcoidal granulomas lack
the associated lymphocytic infiltrate
32 seen
 REFERENCES
1. Chi AC, Damm DD, Neville BW, Allen CM and bouquet J. Colour Atlas and
Maxillofacial diseases. 2019, pp 205-222
2. Kumar V, Abbas AK, Aster JC, Robins and Cotran pathologic basis of
disease.2015
3. Muller S.(2018) Non-infectious Granulomatous Lesions of the Orofacial
Region. Head and Neck pathology.
4. Scully C. Oral and Maxillofacial Medicine. The basis of Diagnosis and
treatment.2013, pages 298-301

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