soft_tissue disease

SOFT-TISSUE DISEASE
BEHCET S DISEASE
BehQet s syndrome was originally defined as a triad of oral
aphthae, genital ulceration and uveitis. However, it is a multisystem
disorder with varied manifestations and termed
Behget s disease. It is rare in the UK and USA but is relatively
common in countries bordering the Mediterranean (BehQet was
a Turk) and very common in Japan. The aetiology is unknown
but is thought to be either an infection or an immunological
reaction to an infectious agent.
Patients are usually young adult males between 20 and 40
years old. Patients suffer one of four patterns of disease, namely:
1. Mucocutaneous (oral and genital ulceration)
2. Arthritic (joint involvement with or without
mucocutaneous involvement)
3. Neurological (with or without other features) or
4. Ocular (with or without other features).
The oral aphthae of Beh£et s disease are not distinguishable
from common aphthae. They are the most consistently found
feature and frequently the first manifestation. Bel^et s disease
should therefore be considered in the differential diagnosis of
aphthous stomatitis particularly in patients in an at-risk racial
group, and the medical history should be checked for the
features shown in Table 13.6. The frequency of other manifestations
is highly variable. As a result there are no absolute
criteria or reliable tests for the diagnosis, but aphthous
stomatitis in combination with any two of the other major
features can be regarded as adequate.
Special tests are not helpful in diagnosis, apart from the
pathergy test. The test is positive if there is an exaggerated
Table 13.6 Diagnostic criteria for Behcet s disease
Major criteria Minor criteria
196
Recurrent oral aphthae
Genital ulceration
Eye lesions
(Recurrent hypopyon, iritis
or iridocyclitis; chorioretinitis)
Skin lesions
(Erythema nodosum,
subcutaneous
thrombophlebitis,
hyperirritability of the skin)
• Arthralgia or arthritis
• Gastrointestinal lesions
• Vascular lesions (mainly
thrombotic) (Fig. 13.6)
• Central nervous system
LICHEN PLANUS

Lichen planus is a common chronic inflammatory disease of
skin and mucous membranes. It mainly affects patients of middle
age or over. Oral lesions have characteristic appearances and
distribution.
Aetiology
In spite of histological changes which can be diagnostic, the
aetiology of lichen planus remains problematical. The predominantly
T-lymphocyte infiltrate suggests cell-mediated
immunological damage to the epithelium and a plethora of
immunological abnormalities has been reported. Though it has
not been possible to demonstrate humoral or lymphocytotoxic
mechanisms, the inflammatory infiltrate consists mainly of T
lymphocytes. Both CD4 and CDS cells are present but numbers
of CDS cells may rise with disease progression and they are
more numerous in relation to the epithelium. Precise trigger
mechanisms remain unclear but lichen planus undoubtedly
appears to be a T-lymphocyte mediated disorder.
Disease indistinguishable from lichen planus, induced by
drugs (notably gold and anti-malarial agents), also suggests
involvement of immunological mechanisms. Oral lichen planus
is also a virtually invariable feature and an early sign of graftversus-
host disease (Ch. 23) but this does not clarify any
immunological mechanisms.
Skin lesions
Lichen planus is a common skin disease but skin lesions are
uncommon in those who complain of oral symptoms. Skin
lesions typically form purplish papules, 2-3 mm across with a
glistening surface marked by minute fine striae and are usually
itchy. Typical sites are the flexor surface of the forearms and
especially the wrists (Fig. 13.12). Skin lesions help, but are not
essential, to confirm the diagnosis of oral lichen planus.
Pathology
Corresponding with their clinical features, lesions fall into
three distinct histological types (Table 13.8).
Typical histological features of atrophic lesions are
summarised in Table 13.9.
Erosions merely show destruction of the epithelium, leaving
only the fibrin-covered, granulating connective tissue floor of
the lesion. Diagnosis depends on seeing atropic lesions or striae
nearby.
Diagnosis
The diagnosis of lichen planus can usually be made on the
history, the appearance of the lesions and their distribution.
However, dysplastic leukoplakias occasionally have a streaky
whitish appearance. A biopsy should be taken, particularly
when striae are ill-defined, plaques are present or the lesions are
in any other ways unusual.
Potent corticosteroids used topically may occasionally
promote thrush as a side-effect. Triamcinolone dental paste
applied to the lesions is an alternative but less effective form of
treatment. Gingival lichen planus is the most difficult to treat.
The first essential is to maintain rigorous oral hygiene.

Corticosteroids should also be used, as already described, and
in this situation triamcinolone dental paste may be useful as it
can readily be applied to the affected gingivae. In unresponsive
cases, tactolimus mouth-rinses may be effective. In exceptionally
severe cases, if topical treatment fails, treatment with
systemic corticosteroids is effective.
Lichenoid reactions
This term is given to lichen planus-like lesions caused by either
systemic drug treatment or those where the histological picture
is not completely diagnostic.
A very wide range of drugs can cause lichenoid reactions of
the skin, mucous membranes or both (Table 13.10). The clinical
features are often indistinguishable from true lichen planus
and usually consist only of white striae. When there is severe
atrophy or ulceration, detecting a possible causative drug may
aid management and a complete drug history is mandatory in
all patients thought to suffer from lichen planus. Some features
which suggest a drug reaction are shown in Table 13.11.
Management
Patients are sometimes concerned that lichen planus is infectious
and should be reassured that this is not so.
Topical application of potent anti-inflammatory corticosteroids
is usually effective but monitoring is required and these
preparations are suitable only for hospital use. Possible
alternatives are to use similar corticosteroids (such as
beclomethasone) from aerosol inhalers used for asthma.
Approximately six puffs from an inhaler can be used to deliver
enough of the corticosteroid to an ulcer. Table 13.10 Some drugs capable of causing lichenoid reactions
These are only the more common causes:
Colloidal gold
Beta-blockers
Oral hypoglycaemics
Allopurinol
Non-steroidal anti-inflammatory drugs
Antimalarials
Methyldopa
Penicillamine
Some tricyclic antidepressants
Thiazide diuretics
Captopril
Check list for management of lichen planus
200
Always check for drugs which might cause a lichenoid reaction.
This is indistinguishable clinically but may respond to a change of
medication
When inflammation worsens or symptoms become more severe
consider the possibility of superinfection with Candida
Biopsy lesions which appear unusual, form homogeneous plaques
or are in unusual sites
Check for skin lesions which may aid diagnosis
Reassure patients that the condition is not usually of great
consequence despite the fact that it can cause constant irritating
soreness. Tell patients that the severity waxes and wanes
unpredictably and the condition may persist for many years
Be aware that squamous carcinoma may develop in lesions,
although very rarely. Follow up lesions associated with reddening,
and any unusual in site, appearance or severity

Onset associated with starting a drug
Unilateral lesions or unusual distributions
Unusual severity
Widespread skin lesions
Localised lesion in contact with restoration
In practice it can be difficult or impossible to differentiate
lichenoid reactions from lichen planus. Many patients are
taking potentially causative drugs, sometimes more than one.
However, these may not be responsible as lichen planus is so
common a disease that its presence may be coincidental. Also,
the drugs often cannot be stopped because of possible medical
adverse effects. Changing to another drug may not be helpful as
the alternative may also cause a reaction
Malignant change in lichen planus
The risk of and possible frequency of malignant change in
lichen planus has long been controversial. Reportedly 1-4% of
patients suffer this complication after 10 years, but there is
growing controversy about such figures. Doubts about the
validity of the diagnosis of lichen planus, in reports of
malignant change, have been expressed — dysplastic lesions,
for example, may have a streaky appearance that has been
mistaken for striae. Also, because lichen planus is so common
a disease, the quoted rates for malignant change would greatly
exceed the actual incidence of oral cancer.
Specific risk factors have also not been identified with
certainty.
CHRONIC ULCERATIVE STOMATITIS
This uncommon mucosal disease is associated with IgG antibodies
to squamous epithelium nuclear protein.
Clinically, females over 40 years are mainly affected. Lesions
are usually erosions, but sometimes lichen planus-like. Some
examples have in fact, been mistaken for lichen planus clinically,
so that it seems possible that antinuclear antibody chronic
ulcerative stomatitis may be more common than is appreciated.
Skin involvement is uncommon.
Histologically, the appearances may be similar to erosive
lichen planus. However, immunofluorescence shows speckled
antinuclear antibodies in the perilesional mucosa and shaggy
deposits of fibrinogen in the basement membrane zone. Serum
shows antinuclear antibody in high litre that reacts with guinea
pig oesophagus substrate but the litre does not correspond wilh
clinical severity. The largel antigen is an epithelial nuclear
protein, which has been shown to be homologous to Ihe p53
lumour suppressor gene.
The mosl effective trealmenl appears to be with chloroquine
or hydroxychloroquine, supplemenled if necessary wilh
prednisolone. However, complete clearance is nol always
achieved or resolution may be followed by relapses. Immunological
changes also persisl after clearance of the lesions. Doses
of chloroquine phosphate or hydroxychloroquine sulphate
should be kepi below 4 mg/kg or 6.5 mg/kg respectively to
minimise Ihe risk of ocular damage. Key features of chronic
ulcerative stomatitis are summarized

PEMPHIGUS VULGARIS
Pemphigus is an uncommon autoimmune disease causing
vesicles or bullae on skin and mucous membranes. Il is usually
falal if untreated. Females usually aged 40-60 years are
predominanlly affected. Lesions often first appear in the moulh


DISEASES OF THE ORAL MUCOSA: NON-INFECTIVE STOMATITIS
but spread widely on the skin. Vesicles are fragile and
infrequently seen intact in the mouth. Residual erosions often
have ragged edges and are superficial, painful and tender Gently stroking the mucosa can cause a vesicle or bulla
to appear (Nikolsky s sign).
Progress of the disease is very variable. It may sometimes be
fulminating with rapid development of widespread oral ulceration,
spread to other sites such as the eyes within a few days,
and very soon afterwards to the skin.
Skin lesions consist of vesicles or bullae varying from a few
millimetres to a centimetre or so across .The bullae
at first contain clear fluid which may then become purulent
Pemphigus vulgaris. Typical oral presentation with erythema,
erosions and persistent ulcers. The surrounding epithelium is friable and
disintegrates on gentle stroking.
or haemorrhagic. Rupture of vesicles leaves painful ragged
erosions. Protein, fluid and electrolytes are lost from the raw
areas and they readily become secondarily infected. Without
treatment, death usually follows, but immunosuppressive treatment
is usually life-saving.
Pathology
An immunopathogenesis can be more convincingly demonstrated
in pemphigus vulgaris than in any other oral disease and
the histological findings are summarised in Table 13.13.
The epithelial cells which lose their attachments become
rounded in shape and the cytoplasm contracts around the nucleus.
Small groups of these rounded-up acantholytic (Tzanck) cells
can often be seen histologically in the contents of a vesicle or
in a smear from a recently ruptured vesicle.
Pemphigus antibodies are tissue-specific and react only to
the epithelial cell surface antigen, an intercellular adhesion
molecule (ICAM), desmoglein 3 . The mechanism
of breakdown of intercellular attachments appears to result
from synthesis of proteases by the epithelial cells.
MUCOUS MEMBRANE (CICATRICIAL) PEMPHIGOID
Mucous membrane pemphigoid is an uncommon chronic disease
causing bullae and painful erosions , Skin involvement
is uncommon and often trivial. The term cicatricial
pemphigoid is sometimes used for this group of diseases, but
particularly applies to ocular involvement where scarring is
prominent and impairs sight.
Lesions . are rarely widespread and progress is
very slow. Desquamative gingivitis can be a manifestation
Nikolsky s sign is typically positive and a striking
clinical finding is sometimes that the epithelium slides away
underneath the edge of a sharp scalpel when a biopsy is attempted.
In the mouth, bleeding into bullae can cause them to appear as
blood blisters. Rupture of erosions leaves raw areas with welldefined
margins. Individual erosions persist for some weeks then
slowly heal. Further erosions may develop nearby and this process
may persist for a year or more. Lesions may remain localised to the
mouth for very long periods and may never involve other sites.

Written by:
Mushtag t. mohammed
4th stage