Chapter 9: Allergies and Immunologic Diseases Flashcards

Clinical Features

localized variant
- involve one to several fungiform papillae
- mildly painful, elevated, red-yellow papules
- occur on anterior dorsal surface of tongue
generalized variant
- involves many fungiform papillae
- sensitive, enlarged, erythematous
- occur on tip and lateral dorsal surface of tongue
papulokeratotic variant
- diffuse involvement of fungiform papillae
- asymptomatic, parakeratotic white-yellow papules
- occur on tip and lateral dorsal surface of tongue

Histopathologic Features

focal areas of exocytosis or ulceration
proliferation of small vascular channels
mixed inflammatory cellular infiltrate
hyperparakeratosis with bacterial colonization

transient lingual papillitis

Tender, yellow-pink papule on the dorsum of the tongue.

transient lingual papillitis, localized

Multiple painful white papules on the lateral dorsum and tip of tongue.

transient lingual papillitis, generalized

Clusters of asymptomatic, elevated, yellow papules on the dorsolateral surface of the tongue.

transient lingual papillitis, papulokeratotic

What is the treatment and prognosis for transient lingual papillitis?

resolves without therapy
topical corticosteroids or anesthetics may be used to reduce pain or duration

Clinical Features

one of the most common oral mucosal pathoses (20%)
T cell–mediated immunologic reaction with production TNF-α
appear to be initiated by some antigenic stimulus
may be associated with systemic disorders
three clinical variations: mild, moderate, herpetaform
occur most in children and young adults (80% before 30 years)

Histopathological Features

central zone of ulceration covered by fibrinopurulent membrane
increased vascularity of connective tissue
mixed inflammatory cellular infiltrate

recurrent aphthous stomatitis

Clinical Features

fewest recurrences and shortest duration
arise on nonkeratinized mucosa, especially buccal and labial
yellow-white, fibrinopurulent membrane with erythematous halo
between 3 and 10 mm in diameter
heal in 7 to 14 days without scarring
one to five lesions at a time
disproportionately painful

minor aphthous ulceration

Clinical Features

largest lesions and longest duration
measure 1 to 3 cm in diameter
yellow-white ulceration with red halo
take from 2 to 6 weeks to heal and may cause scarring
occur most on labial mucosa, soft palate, tonsillar fauces
onset after puberty

major aphthous ulceration

Clinical Features

greatest number of lesions and most frequent recurrences
measure 1 to 3 mm in diameter
up to a hundred present at once
superficial resemblance to primary HSV infection
may coalesce into larger irregular ulcerations
heal within 7 to 10 days
occur on nonkeratinized, movable mucosa
female predominance, with onset in adulthood

herpetiform aphthous ulceration

Erythematous halo encircling a yellowish ulceration of the soft palate on the left side.

minor aphthous ulceration

Two ulcerations of different sizes located on the maxillary labial mucosa.

minor aphthous ulceration

Single ulceration of the anterior buccal mucosa.

minor aphthous ulceration

Large, deep, and irregular ulceration of the posterior buccal mucosa. Note extensive scarring of the anterior buccal mucosa from previous ulcerations.

major aphthous ulceration

Large, irregular ulceration of the soft palate.

major aphthous ulceration

Numerous pinhead ulcerations of the ventral surface of the tongue, several of which have coalesced into larger, more irregular areas of ulceration.

herpetiform aphthous ulceration

Aphthous ulcerations that heal within 1 to 2 weeks and recur infrequently.

simple aphthosis

Aphthous ulcerations that occur in multiples and develop continuously.

complex aphthosis

How is recurrent aphthous stomatitis diagnosed?

No laboratory procedure provides definitive diagnosis; the diagnosis is made from the clinical presentation and from exclusion of other diseases.

What is the treatment and prognosis for recurrent aphthous stomatitis?

topical corticosteroids (e.g. dexamethasone, fluocinonide) for mild disease
potent corticosteroids (e.g. triamcinolone, clobetasol) for major disease
in resistant cases, systemic corticosteroids may be required for control
complex aphthosis demands thorough evaluation for systemic disease

Large ulceration of the left anterior buccal mucosa.
Same lesion after 5 days of therapy with betamethasone syrup used in a swish-and-swallow method. The patient was free of pain by the second day of therapy. The ulceration healed completely during the next week.

major aphthous ulceration

Clinical Features

chronic ocular inflammation and orogenital ulcerations
systemic vasculitis caused by an abnormal immune process
usually arises in the third and fourth decades
increased prevalence and worse clinical course in men
oral lesions similar to aphthous ulcers often herald onset
genital lesions (papules, vesicles, pustules, etc.) in 75% of cases
positive skin “pathergy”
self-limiting and nondeforming arthritis
ocular involvement (uveitis, conjunctivitis, etc.) in 70% of cases
vascular disease often presents as thrombophlebitis
variable gastrointestinal disease (pain, anorexia, diarrhea, etc.)
CNS involvement (paralysis, dementia) in 10% to 25% of cases

Histopathological Features

leukocytoclastic vasculitis
similar to aphthous stomatitis

Behçet syndrome

Diffuse erythema surrounding numerous irregular ulcerations of the soft palate. Oral ulcerations often herald the onset of this disease.

Behçet syndrome

Numerous irregular ulcerations of the labia majora and perineum as part of a disease characterized by chronic ocular inflammation and orogenital ulcerations.

Behçet syndrome

Sterile pustule of the skin that developed 1 day after injection of saline. This reaction is termed cutaneous pathergy.

Behçet syndrome

From a diagnostic standpoint, one of the most important skin manifestations in Behçet syndrome is the presence of positive “pathergy.” What does this refer to?

One or 2 days after the oblique insertion of a needle under sterile conditions, a tuberculin-like skin reaction or sterile pustule develops.

No laboratory finding is diagnostic of Behçet syndrome. What In an attempt to standardize diagnoses, five definitive criteria have been developed. What are they?

recurrent oral ulceration, plus and two of the following:
recurrent genital ulcerations
eye lesions
skin lesions
positive pathergy test

What is the treatment and prognosis for Behçet syndrome?

most treatment is symptomatic until the disease goes into remission
old or female patients have a better prognosis than male or young
ocular lesions or CNS involvement mandate more aggressive therapy
systemic medications include azathioprine, colchicine, corticosteroids
orogenital ulcerations respond to topical or intralesional corticosteroids
relapsing and remitting pattern, with attacks lessening after 5 to 7 years

Clinical Features

arises prior to age 50, with predilection for females and blacks
acute cases exhibit fever, fatigue, anorexia, or weight loss
chronic cases exhibit pulmonary symptoms
affects lungs, lymph nodes, skin, eyes, and salivary glands
chronic, violaceous, indurated skin lesions ("lupus pernio")
scattered, tender erythematous nodules ("erythema nodosum")
ocular involvement (25%) often appears as anterior uveitis
salivary gland involvement results in enlargement and xerostomia
submucosal masses, isolated papules, granularity, or ulcerations
occur on buccal mucosa, gingiva, lips, tongue, and palate

Histopathological Features

granulomatous inflammation
aggregates of epithelioid histiocytes
surrounding rim of lymphocytes
scattered Langhans' or foreign body type giant cells
laminated, basophilic, calcified lysosomes ("Schaumann bodies")
stellate inclusions of trapped collegen ("asteroid bodies")

sarcoidosis

Violaceous indurated plaques of the right malar area and bridge of nose.

lupus pernio (sarcoidosis)

Multiple erythematous macules of the hard palate. Oral lesions are uncommon in this disease, but may be normal in color, brown-red, violaceous, or hyperkeratotic.

sarcoidosis

Erythematous macules with central hyperkeratosis of the lower labial mucosa. Oral lesions are uncommon in this disease.

sarcoidosis

Labial minor salivary gland demonstrating granulomatous inflammation characterized by circumscribed collections of histiocytes, lymphocytes, and multinucleated giant cells.

sarcoidosis

Multinucleated giant cell with intracytoplasmic asteroid body, a stellate inclusion consisting of entrapped fragments of collagen.

sarcoidosis

A clinical syndrome associated with acute sarcoidosis consisting of erythema nodosum, bilateral hilar lymphadenopathy, and arthralgia.

Löfgren syndrome

A clinical syndrome associated with acute sarcoidosis consisting of parotid enlargement, anterior uveitis of the eye, facial paralysis, and fever.

Heerfordt syndrome (uveoparotid fever)

How is sarcoidosis diagnosed?

The diagnosis is established by clinical and radiographic presentations, the histopathologic appearance, and negative tests for casative organisms.
Elevated serum angiotensin-converting enzyme (ACE) levels supports the diagnosis, but is reported in only 60% of patients with the disease.
In the past, the Kveim test, was performed by intradermal injection of a sterilized suspension of human sarcoid tissue.

What is the treatment and prognosis for sarcoidosis?

symptoms may resolve spontaneously within 2 years (60%)
intervention is recommended for progressive disease
corticosteroids remain first-line therapy
resistance and relapses are common
resolution may not occur even with treatment (10% to 20%)
patients may die of pulmonary, cardiac, or CNS complications (4% to 10%)

Clinical Features

primarily affects adults, but can occur at any age
nontender, persistent swelling involving lips
may be combined with facial paralysis and fissured tongue
intraoral lesions including edema, ulcers, and papules
tongue may develop fissures, edema, paresthesia, or erosions
gingiva can develop swelling, erythema, or pain
buccal mucosa often exhibits a cobblestone
linear hyperplastic folds may occur in the sulcus

Histopathological Features

edema in superficial lamina propria
dilation of lymphatic vessels
scattered lymphocytes
fibrosis in long-term lesions
noncaseating granulomatous inflammation
granulomas clustered around scattered vessels

orofacial granulomatosis

The variant of orofacial granulomatosis in which there is nontender, persistent swelling of the lips combined with facial paralysis and a fissured tongue.

Melkersson-Rosenthal syndrome

The variant of orofacial granulomatosis in which there is nontender, persistent swelling of the lips in isolation.

cheilitis granulomatosa (of Miescher)

Nontender, persistent enlargement of the upper lip. This patient did not present with facial paralysis nor a fissured tongue.

cheilitis granulomatosa (orofacial granulomatosis)

Persistent enlargement of the lower lip. This patient also presented with numerous furrows on the dorsal surface of the tongue.

Melkersson-Rosenthal syndrome (orofacial granulomatosis)

Note numerous furrows on the dorsal surface of the tongue. This patient also presented with persistent enlargement of the lower lip.

Melkersson-Rosenthal syndrome (orofacial granulomatosis)

Hyperplastic mucosa noted bilaterally in the mandibular mucobuccal fold with elongated ulcerations in the base of these folds.

orofacial granulomatosis

Clusters of granulomatous inflammation around scattered vessels. The inset illustrates the histiocytes and multinucleated giant cells within the granulomas.

orofacial granulomatosis

How is orofacial granulomatosis diagnosed?

Based on histopathologic demonstration of granulomatous inflammation that is associated with negative special stains for organisms and no foreign material.

What is the treatment and prognosis for orofacial granulomatosis?

first goal of management is discovery of initiating cause
intralesional delayed-release high-concentrate triamcinolone
prognosis is highly variable; some lesions resolve spontaneously

Diffuse enlargement of the upper lip.
Same patient after intralesional triamcinolone injections.

orofacial granulomatosis

Clinical appearance before local therapy.
Significant resolution after intralesional corticosteroid therapy.

orofacial granulomatosis

Clinical Features

wide age range (mean, 41 years), 90% in Caucasians
necrotizing granulomatous lesions of respiratory tract (limited)
may also exhibit necrotizing glomerulonephritis (generalized)
may exhibit lesions of the skin and mucosa (superficial)
nasal drainage, sinus pain, nasal ulceration (URT involvement)
dry cough, hemoptysis, dyspnea, chest pain (LRT involvement)
proteinuria and red blood cell casts (renal involvement)
florid and granular ginvival hyperplasia ("strawberry gingivitis")
oral ulcerations (usually diagnosed at a later stage)
salivary gland enlargement

Histopathological Features

mixed inflammation centered around blood vessels
heavy neutrophilic infiltration, necrosis, and nuclear dust
inflammatory cellular infiltrate
pseudoepitheliomatous hyperplasia and subepithelial abscesses
prominent vascularity with extensive red blood cell extravasation

Wegener granulomatosis

Florid and granular gingival hyperplasia with hemorrhagic and friable bulbous projections ("strawberry gingivitis").

Wegener granulomatosis

Hyperplastic and hemorrhagic mucosa of the facial mandibular gingiva on the left side. This red, bumpy surface is responsible for the strawberry-like appearance

Wegener granulomatosis

Deep, irregular ulceration of the hard palate on the left side. These represent late-stage disease; more than 60% of patients will have renal involvement.

Wegener granulomatosis

Connective tissue containing proliferation of numerous vascular channels and a heavy inflammatory infiltrate consisting of lymphocytes, neutrophils, eosinophils, and multinucleated giant cells.

Wegener granulomatosis

Gingival biopsy specimen showing a mixed inflammatory cellular infiltrate obscured by extensive extravasation of red blood cells.

Wegener granulomatosis

The American College of Rheumatology proposed four diagnostic criteria with a minimum of two required for a diagnosis of Wegener granulomatosis. What are these criteria?

oral ulcerations or nasal discharge
nodules, fixed infiltrates, or cavities on chest radiograph
abnormal urinary sediment (e.g. RBCs or casts
granulomatous inflammation upon biopsy

What marker is the most useful in the diagnosis of Wegener granulomatosis, seen in 90% to 95% of generalized cases and 60% of the early or localized cases?

antibodies against proteinase-3 (PR3-ANCA)

What is the treatment and prognosis for Wegener granulomatosis?

mean survival of untreated patients with generalized disease is 5 months
80% of the patients are dead at 1 year and 90% within 2 years
prognosis is better for the limited and superficial forms
first line therapy is oral prednisone and cyclophosphamide
prolonged remission is noted in up to 75% of affected patients
for maintenance, cyclophosphamide may be replaced with methotrexate
relapse rate up to 30%, maintenance therapy is necessary in many patients

The risk of an adverse reaction is approximately ___% with the use of two medications, ___% with five drugs, and almost ___% with eight or more.

6%, 50%, 100%

What is a Type A drug reaction?

An exaggerated but otherwise expected pharmacologic action of the prescribed medication (e.g. bleeding associated with warfarin).

What is a Type B drug reaction?

An idiosyncratic reaction that is not expected, usually arising from immune-mediated effects (e.g. hypersensitivity reactions).

A reaction of the oral mucosa to the systemic administration of a medication.

stomatitis medicamentosa

Several different patterns of stomatitis medicamentosa exist. What are the seven classes of mucosal reactions to systemic drug administration?

anaphylactic stomatitis
intraoral fixed drug eruptions
lichenoid drug reactions
pemphigoid-like drug reactions
pemphigus-like drug reactions
lupus erythematosus–like eruptions
nonspecific erosive, ulcerative, or aphthous-like lesions

Clinical Features

various patterns of mucosal alterations
erythema or aphthous-like ulcerations
localized areas of erythema and edema
vesiculoerosive lesions of the labial mucosa
lupus-, pemphigoid-, or pemphigus-like lesions
bilateral and symmetrical lesions are common

Histopathological Features

nonspecific pattern of subacute mucositis
mixed inflammatory cellular infiltrate
spongiosis and exocytosis of the epithelium
lupus-, pemphigoid-, or pemphigus-like findings
DIF for IgG shows annular pattern along basal cell layer ("sting of pearls")
may detect circulating antibody ("basal cell cytoplasmic antibody")

mucosal reactions to systemic drug administration

Bilateral erosions of lower labial mucosa with intermixed striae. Biopsy revealed lichenoid pattern of mucositis but with numerous plasma cells intermixed with the lymphocytes.
Same patient depicted in A after discontinuation of simvastatin.

allergic mucosal reaction to systemic drug administration

Irregular area of superficial erosion of the left buccal mucosa. Lesions were also present on the contralateral buccal mucosa and bilaterally on the lateral borders of the tongue. Lesions disappeared after discontinuing allopurinol.

lichenoid drug reaction

Large irregular erosion of the right ventral surface of the tongue. The lesion arose secondary to use of oxaprozin, a nonsteroidal antiinflammatory drug (NSAID).

allergic mucosal reaction to systemic drug administration

How are mucosal reactions to systemic drug administration diagnosed?

identify potentially offending medication through detailed medical history and establish a temporal relationship with the mucosal alteration
1. if more than one suspected, start with most recently added
2. if last-introduced drug is not responsible, do serial elimination
definitive diagnosis can be made if mucosal alterations resolve after discontinuation of medication and recur on reintroduction
presumptive diagnosis usually is sufficient and justified when the mucosal alterations clear after cessation of the offending medication
for lupus-like reactions, consider serum evaluation for ANAs dsDNA Ab

What is the treatment for mucosal reactions to systemic drug administration?

discontinue and replace causative drug and if possible
lesions can be resolved with topical corticosteroids
If discontinuation is contraindicated, palliative care can be provided

Clinical Features

can be acute or chronic
distinct female predominance
can be localized or diffuse
burning is the most frequent symptom
mucosa may be barely red to brilliantly erythematous
superficial ulcerations occasionally arise
muscosa may be white and hyperkeratotic
desquamation of the superficial layers of the epithelium
dryness, scaling, fissuring, or cracking of the vermilion border

allergic contact stomatitis

Mucosal erythema and vesicles of the lower labial mucosa caused by use of aluminum chloride on gingival retraction cord.

allergic contact stomatitis

Erythematous mucosa with superficial epithelial desquamation. This patient reported recently changing brands of toothepaste.

allergic contact stomatitis

How is allergic contact stomatitis diagnosed?

diagnosis of acute contact stomatitis is straightforward due to temporal relationship between agent and resultant eruption
diagnosis of chronic contact stomatitis is more difficult, requirring good oral health and elimination of all other possible causes

What is the treatment and prognosis for allergic contact stomatitis?

for mild acute cases, simply removal of suspected allergen
for severe acute cases, antihistamines and topical anesthetics
for chronic cases, topical corticosteroid gel or oral suspension
use of plain baking soda or flavor-free toothpaste
avoidance of mouthwash, gum, mints, chocolate, cinnamon products

Clinical Features

associated with use of potent corticosteroids on face
worsened by exposure to UV light, heat, and wind
persistent erythematous papules, vesicles, and pustules
occur on skin surrounding the vermilion border
may involve perinasal skin (40%)
zone of spared skin adjacent to vermilion border
most occurs in women between ages of 20 to 45 years

Histopathologic Findings

chronic lymphohistiocytic dermatitis with spongiosis of hair follicles
rosacea-like pattern with perifollicular granulomatous inflammation
may be misdiagnosed as sarcoidosis

perioral dermatitis

Multiple erythematous papules of the skin surrounding the vermilion border of the lips. Note similar involvement around the nasal orifices.

perioral dermatitis

What is the treatment for perioral dermatitis?

discontinue corticosteroids, cosmetics, facial creams (“zero therapy”)
oral tetracycline is "gold standard," except in childhood and pregnancy
responds well to topical pimecrolimus or topical erythromycin
improvement within weeks, resolution in months, recurrence uncommon

Clinical Features

associated with candy, chewing gum, and toothpaste
pain and burning are common in all cases
affects gingiva, buccal mucosa, lateral borders of tongue
may resemble plasma cell gingivitis
enlargement, edema, and erythema
hyperkeratosis of surface epithelium

Histopathologic Findings

acanthotic, often with elongated rete ridges
thinning of the suprapapillary plates
hyperkeratosis and extensive neutrophilic exocytosis
heavy inflammatory cell infiltrate