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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5210_Библиотеки_им_академика_М_И_Перельмана
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11.3.2.1.3 Testing for HIV Infection
The screening test for HIV infection is an enzyme- linked immunosorbent assay (ELISA) to detect
HIV p24 antibodies. This screening test is confirmed with the Western blot test, which detects
antibodies to several viral proteins. Alternatively, HIV DNA sequences may also be detected using
polymerase chain reaction (PCR).
11.3.2.1.4 Treatment
Anti- retroviral therapy must be initiated for effective control when CD4+ T- helper cell counts reach
3
350 cells/mm
or when the viral load is 100,000 copies/ml. The therapy calls for a cocktail of drugs.
Anti- HIV drugs are classified according to their mechanisms of action into nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, cell fusion
inhibitors, CCR5 inhibitors and integrase inhibitors. Three synergistic drugs from two different
classes are used, known as Highly Active Antiretroviral Therapy (HAART). HAART therapy reduces
viremia and normalises CD4+ T- cell counts with a resultant reduction in mortality. They do require
lifelong administration as HIV is not eliminated. In addition, opportunistic and other infections will
require management as well. Increased incidence of drug- related allergic reactions and immune
reconstitution inflammatory syndrome (IRIS) have been noted in patients receiving HAART
therapy. An effective vaccine has eluded researchers due to frequent mutations by HIV(8).
11.4 Autoimmune Erosive andVesiculobullous Disorders
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Many autoimmune erosive and vesiculobullous disorders manifest in the oral cavity. In some, the
oral presentation is first. The range of oral lesions can be from asymptomatic crisscrossing white
lines to short- lasting vesicles, bullae and painful erosions and ulcers. While any oral mucosa may
be affected, gingival involvement is common. Disorders include pemphigus vulgaris, mucous
membrane pemphigoid (MMP), lichen planus, lichen planus pemphigoides (LPP) and chronic
ulcerative stomatitis (CUS). Lupus erythematosus is also included among such lesions and has
been discussed earlier. Other infrequent conditions include paraneoplastic pemphigus, bullous
pemphigoid and linear IgA disease. Also, while diseases such as erythema multiforme and graft
versus host disease present as oral ulcerations and erosions, they are immune system mediated but
not autoimmune in etiopathogenesis.
11.4.1 Pemphigus
Pemphigus is a group of autoimmune disorders that include conditions such as pemphigus vulgaris, pemphigus vegetans, pemphigus erythematosus, pemphigus foliaceous, pemphigus herpetiformis, IgA pemphigus and IgA/IgG pemphigus.
11.4.1.1 Oral Pemphigus
Pemphigus vulgaris is the most common type with oral manifestations. Often, oral lesions are the
first to show. Women aged 40– 60 years are predominantly affected. People of Jewish and Indian
origin are predisposed. Oral blisters occur on the buccal mucosa, ventral tongue and floor of the
mouth in over 60% of cases. Skin lesions usually follow oral lesions. Blisters are filled with clear
fluid. Blisters rupture quickly, leaving painful erosions/shallow ulcers. Lateral sliding force or
gentle stroking on the uninvolved skin or mucosa can produce a surface slough or induce vesicle
formation (Nikolsky’s sign).
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Patients with pemphigus demonstrate serum immunoglobulin IgG against epithelial cell surface
glycoproteins desmoglein one and desmoglein 3, integral components of the intercellular adhesion
complex desmosomes. While desmoglein one and desmoglein three are expressed in the epidermis
and oral epithelium, expression of desmoglein 1in the oral epithelium is limited. The resultant
antigen- antibody reaction causes cells to separate (acantholysis) (Figure 11.14). Free- floating
acantholytic cells are called Tzanck cells (Figure11.15)– the cytosol of acantholytic cells pools to
cause intraepithelial blisters. Acantholysis is seen in biopsies of perilesional tissue. Direct immunofluorescence studies show IgG (Figure11.16) and complement three (Figure11.17) at the epithelial cell membranes of the spinous layer. Indirect immunofluorescence is also positive in about
80% of cases. The intraepithelial acantholytic process results in desquamation of the superficial
layers of the epithelium. This finding can be elicited upon applying gentle oblique pressure over
Figure11.14 Acantholysis and intraepithelial clefting in pemphigus vulgaris.
Figure11.15 Acantholytic Tzanck cells in pemphigus vulgaris.
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Figure11.16 Direct immunofluorescence demonstrating IgG at cell membrane of individual epithelial
cells in pemphigus vulgaris.
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Figure11.17 Direct immunofluorescence demonstrating C3 at cell membrane of individual epithelial cells
in pemphigus vulgaris.
perilesional unaffected mucosa. This is known as the Nikolsky sign. Acantholysis and desquamation result in superficial ragged erosions of the buccal mucosa, soft palate, labial mucosa, floor of
mouth, gingiva and lateroventral tongue. Vesicles form but rupture early. Bleeding, pain, soreness
and inability to perform oral functions, including eating, are presenting symptoms. In about 50%
of cases, oral lesions may be the only manifestation of the disease. Skin lesions present as flaccid
bullae that rupture quickly to leave denuded skin erosions. Conjunctivitis is rare. Management of
pemphigus vulgaris includes induction with systemic prednisone followed by maintenance and
long- term control with rituximab and mycophenolate mofetil(9, 10).
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11.4.2 Mucous Membrane Pemphigoid
MMP, also known as cicatricial pemphigoid, is a group of autoimmune blistering, desquamating,
and erosive conditions that affect mucous membranes predominantly. The blistering and desquamation result from antibodies directed against the basement membrane zone’s antigens. The antigens represented include BP180, BP230, laminin- 332 (epiligrin), laminin- γ1 and α6β4integrin.
Although the antigens are heterogeneous, the ensuing clinical features are identical. MMP is more
common in women and affects those in their fifth or sixth decades. While oral lesions are the
most prevalent manifestation of MMP, lesions of the conjunctiva, nasal, oesophageal, laryngeal
and genital mucosa may be seen. Gingival involvement in desquamative gingivitis is common
(Figure11.18). Other oral sites may be affected, too. Blistering with vesicle formation may be seen
in the oral mucosa occasionally. As the vesicles rupture, large irregular ulcers develop. Symptoms
include pain, burning, bleeding and inability to chew and maintain oral hygiene. Patients with
extensive lesions involving the horopharynx and surrounding tissue experience sore throat, hoarseness, nasal stuffiness, epistaxis and a postnasal drip. Conjunctival disease results in entropion of
eyelashes and symblepharon formation (Figure 11.19), with progressive scarring resulting in
Figure11.18 Early lesions of desquamative gingivitis in a patient with mucous membrane pemphigoid.
Figure11.19 Symblepharon formation in a patient with ocular mucous membrane pemphigoid.
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blindness. A biopsy of perilesional tissue shows a subepithelial clefting process (Figures11.20
and11.21). Direct immunofluorescence studies indicate the presence of IgG (Figure11.22), IgA
and C3 (Figure11.23) at the basement membrane zone. The mainstay of management of MMP is
topical corticosteroid application. Gingival lesions may benefit from a custom- fabricated tray to
hold the steroid against affected tissue. A combination of tetracycline and niacinamide in systemic
divided doses of 0.5– 2.0 g each is used in milder cases. Other drugs and therapies include dapsone,
mycophenolate mofetil, azathioprine, methotrexate and rituximab. Patients with oral MMP must
be referred to an ophthalmologist for evaluation for ocular disease(9, 10).
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Figure11.20 Biopsy of perilesional tissue shows a subepithelial clefting process in mucous membrane
pemphigoid.
Figure11.21 The subepithelial clefting process results in separation of the entire epithelium from the
underlying connective tissue.
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Figure11.22 Direct immunofluorescence shows a linear patern of reactivity of IgG at the basement
membrane in mucous membrane pemphigoid.
Figure11.23 Direct immunofluorescence shows basement membrane deposits of complement 3in
mucous membrane pemphigoid.
11.4.3 Lichen Planus
Lichen planus is considered an autoimmune disorder, although the target antigen remains elusive,
and direct immunofluorescence studies only demonstrate antibodies to human fibrinogen at the
basement membrane. The immune response in LP involves CD4+ and CD8+ T- lymphocytes, NK
cells, mast cells and dendritic cells. B- lymphocytes and antibodies do not play a pathogenetic role as
in other autoimmune mucocutaneous vesiculoerosive blistering diseases like MMP or PV. Cutaneous
LP presents as multiple, purple, polygonal papules that cluster at the wrist, skin over the shin and
the small of the back. The lesions show fine, lacelike, white striae known as Wickham striae. The
lesions are intensely pruritic. Genital lesions and nail dystrophy may also be seen.
11.4.3.1 Oral Lichen Planus
Up to 60% of patients with cutaneous LP may show oral lichen planus (OLP). OLP may present by
itself. Only 15% of OLP cases demonstrate cutaneous lesions. OLP occurs more commonly in
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women between the ages of 30 and 80 years. Persons of colour may show post- inflammatory melanosis underlying lesions of OLP. Patterns of OLP described include reticular (annular), atrophic/
erosive, popular, plaque types and bullous types. Reticular OLP is by far the most common oral
presentation. Lesions are widespread and bilateral and present as crisscrossing white lines
(Wickham striae) that intersect and create patterns such as a net (reticular) or rings (annular)
(Figure11.24). Lesions of reticular OLP are primarily asymptomatic. Rarely patients may complain of a feeling of roughness and reduced flexibility. Gingival disease is almost always erosive
(Figures11.25 and11.26), with symptoms including pain, soreness, bleeding, intolerance to spicy
and acidic foodstuffs and inability to maintain oral hygiene. Lesions of erosive OLP may extend to
involve other oral surfaces. Erosive lesions show fine white striae at the periphery. Erosive gingival
lesions may result in desquamation. This presentation is often called a bullous OLP. Dorsum
tongue lesions appear as white plaques and patches with fine striae noted at the peripheries. Plaque
type mimics oral leukoplakia. Superficial mucoceles may also accompany OLP. Lesions of OLP
may need to be differentiated from other conditions such as chronic graft- versus- host disease,
lichenoid drug reactions, lichenoid contact metal and hypersensitivity (non- metal dental materials
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Figure11.24 Annular lesions of lichen planus on the buccal mucosa.
Figure11.25 Erosive lichen planus on the gingiva.
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Figure11.26 Lesions of erosive lichen planus on the palatal gingiva. Note the fine white striae at the
periphery of the erosive lesions.
Figure11.27 Lesions of lichen planus may show hyperkeratosis with variable degree of epithelial
hyperplasia. The superficial lamina propria shows chronic inflammation consisting predominantly of
lymphocytes.
and artificial flavouring agents) reactions, lupus erythematosus, CUS and MMP. Histopathological
features of OLP include hyperkeratosis without a verrucoid surface architecture, variable degree of
epithelial hyperplasia (Figure11.27) saw- tooth- like epithelial rete ridges, liquefaction degeneration of basal cells with colloid/Civatte body formation in the basal layer of epithelium or the superficial lamina propria (Figures11.28 and11.29), a band of eosinophilic material at the basement
membrane region, a band- like zone of cellular infiltrate consisting of lymphocytes in the superficial lamina propria, and absence of epithelial dysplasia. Direct immunofluorescence studies show
a fuzzy fibrinogen band at the basement membrane (Figure11.30). Management of OLP is directed
towards symptomatic lesions. Therapy includes Class I and II potent topical corticosteroids in gel
formulations, including fluocinonide, triamcinolone, clobetasol propionate and betamethasone.
Other drugs include systemic steroids, hydroxychloroquine, azathioprine, systemic retinoids, phototherapy using psoralen UV A light (PUVA), and calcineurin inhibitors such as cyclosporin,
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Figure11.28 Basal cell degeneration gives the epithelial rete ridges a sawtooth- like appearance.
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Figure11.29 Eosinophilic colloid/Civatte bodies are seen in the basal epithelium and in the superficial
lamina propria in lichen planus.
tacrolimus and pimecrolimus. There is controversy about the malignant transformation of OLP;
therefore, any case demonstrating histopathological evidence of dysplasia must be treated as dysplasia, not lichen planus(11, 12).
11.4.4 Lichen Planus Pemphigoides
LPP is a rare autoimmune blistering disease that happens in the setting of lichen planus. While it
primarily affects the skin, cases involving the oral mucosa alone have been reported(13). Vesicles
and bullae resembling MMP or bullous pemphigoid form and in the oral cavity progress to erosions
and ulcerations. These lesions arise over or in the proximity of lesions of lichen planus.
Histopathological examination of biopsied perilesional tissue exhibits features of lichen planus
and pemphigoid (Figures11.31– 11.33). Direct immunofluorescence study shows linear IgG, C3
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Figure11.30 Direct immunofluorescence shows shaggy deposits of fibrinogen at the basement
membrane in lichen planus.
Figure11.31 Histopathology of a case of lichen planus pemphigoides showing features of lichen planus
(also see Figures11.32 and 11.33).
Figure11.32 Frozen section stained with haemotoxylin and eosin stains shows features of lichen planus
(see Figure11.33).
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