leziuni veziculo-buloase

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Bullous pemphigoid pathology Bullous pemphigoid is the most common autoimmune dermatosis presenting with crops of tense pruritic blisters, often in older adults. Mucosal involvement may occur and a number of clinical subtypes exist. Autoantibodies are directed to components of the basement membrane, particularly the BP antigens BP180 and BP230. Histology of bullous pemphigoid Early lesions during the urticarial phase may be non-specific and show mild upper dermal oedema with perivascular infiltrate (figure 1). There are often conspicuous eosinophils. Immunofluorescence is very helpful in this early phase. Established blister: The blister is subepidermal and contains fibrin and large numbers of inflammatory cells including eosinophils (figures 2, 3). The eosinophils may be very dense in areas and form small abscesses in the superficial dermis. Bullous pemphigoid pathology Figure 1 Figure 2 Figure 3 Figure 4 Special studies of bullous pemphigoid Direct immunofluorescence shows linear deposition of IgG (most often IgG4 subtype) and C3 along the basement membrane (figure 4). Split skin indirect immunofluorescence studies are generally not needed, but may be useful in rare cases when epidermolysis bullosa aquisita is suspected. Differential diagnosis of bullous pemphigoid Dermatitis herpetiformis : Neutrophil dermal papillary microabscesses seen in dermatitis herpetiformis are not usually present in bullous pemphigoid but may be present in some variants. Direct immunofluorescence shows granular deposition of IgA. Linear IgA disease: Subepidermal blister formation with linear basement membrane IgA deposition on direct immunofluorescence. Epidermolysis bullosa aquisita shows subepidermal bullae with linear IgG/C3 deposition however indirect immunofluorescence in these condition reveals positivity on the floor of split skin whereas bullous pemphigoid has positivity on the epidermal side. Other causes of subepidermal blistering include epidermolysis bullosa, porphyria cutanea tarda and bullous amyloidosis .

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Page 1: leziuni veziculo-buloase

Bullous pemphigoid pathologyBullous pemphigoid is the most common autoimmune dermatosis presenting with crops of tense pruritic blisters, often in older adults. Mucosal involvement may occur and a number of clinical subtypes exist. Autoantibodies are directed to components of the basement membrane, particularly the BP antigens BP180 and BP230.

Histology of bullous pemphigoid

Early lesions during the urticarial phase may be non-specific and show mild upper dermal oedema with perivascular infiltrate (figure 1). There are often conspicuous eosinophils. Immunofluorescence is very helpful in this early phase.

Established blister: The blister is subepidermal and contains fibrin and large numbers of inflammatory cells including eosinophils (figures 2, 3). The eosinophils may be very dense in areas and form small abscesses in the superficial dermis.

Bullous pemphigoid pathology

 

Figure 1

 

Figure 2

 

Figure 3

 

Figure 4

Special studies of bullous pemphigoid

Direct immunofluorescence shows linear deposition of IgG (most often IgG4 subtype) and C3 along the basement membrane (figure 4). Split skin indirect immunofluorescence studies are generally not needed, but may be useful in rare cases when epidermolysis bullosa aquisita is suspected.

Differential diagnosis of bullous pemphigoid

Dermatitis herpetiformis: Neutrophil dermal papillary microabscesses seen in dermatitis herpetiformis are not usually present in bullous pemphigoid but may be present in some variants. Direct immunofluorescence shows granular deposition of IgA.

Linear IgA disease: Subepidermal blister formation with linear basement membrane IgA deposition on direct immunofluorescence.

Epidermolysis bullosa aquisita shows subepidermal bullae with linear IgG/C3 deposition however indirect immunofluorescence in these condition reveals positivity on the floor of split skin whereas bullous pemphigoid has positivity on the epidermal side.

Other causes of subepidermal blistering include epidermolysis bullosa, porphyria cutanea tarda and bullous amyloidosis.

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Erythema multiformeFrom Wikipedia, the free encyclopedia

Erythema multiforme

Classification and external resources

Erythema multiforme minor of the hands ( note the blanching centers of

the lesion )

Erythema multiforme is a skin condition of unknown cause, possibly mediated by deposition of immune complex (mostly IgM) in the superficial microvasculature of the skin and oral mucous membrane that usually follows an infection or drug exposure. It is an uncommon disorder, with peak incidence in the second and third decades of life.

Presentation[edit]

The condition varies from a mild, self-limited rash (E. multiforme minor)[1] to a severe, life-threatening form known as erythema multiforme major (or erythema multiforme majus) that also involves mucous membranes.

Consensus classification:

Erythema multiforme minor - Typical targets or raised, edematous papules distributed acrally Erythema multiforme major - Typical targets or raised, edematous papules distributed acrally

with involvement of one or more mucous membranes; epidermal detachment involves less than 10% of total body surface area (TBSA)

SJS/TEN - Widespread blisters predominant on the trunk and face, presenting with erythematous or pruritic macules and one or more mucous membrane erosions; epidermal detachment is less than 10% TBSA for Steven-Johnson syndrome and 30% or more for toxic epidermal necrolysis.

[2]

The mild form usually presents with mildly itchy (but itching can be very severe), pink-red blotches, symmetrically arranged and starting on the extremities. It often takes on the classical "target lesion" appearance,[3] with a pink-red ring around a pale center. Resolution within 7–10 days is the norm.

Individuals with persistent (chronic) erythema multiforme will often have a lesion form at an injury site, e.g. a minor scratch or abrasion, within a week. Irritation or even pressure from clothing will cause the erythema sore to continue to expand along its margins for weeks or months, long after the original sore at the center heals.

Symptoms

Fever

General ill feeling

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Itching  of the skin

Joint aches

Multiple skin lesions that:o Start quickly and may return

o May spread

o May appear as a nodule, papule, or macule and may look like hives

o Have a central sore surrounded by pale red rings, also called a "target", "iris", or

"bulls-eye"o May have vesicles and blisters of various sizes (bullae)

o Are located on the upper body, legs, arms, palms, hands, or feet

o May involve the face or lips

o Are usually even on both sides (symmetrical)

Other symptoms may include:

Bloodshot eyes

Dry eyes

Eye burning, itching, and discharge

Eye pain

Mouth sores

Vision problems

Exams and Tests

You doctor will look at your skin to diagnose this problem and ask if you have a history of risk factors

or related diseases.

Tests may include:

Nikolsky's sign

Skin lesion biopsy

Examination of skin tissue undera microscope

Causes[edit]

See also: List of human leukocyte antigen alleles associated with cutaneous conditions

Many suspected aetiologic factors have been reported to cause EM.[4]

Infections: Bacterial (including Bacillus Calmette-Guérin (BCG) vaccination, haemolytic Streptococci, legionellosis, leprosy, Neisseria meningitidis, Mycobacterium,Pneumococcus, Salmonella species, Staphylococcus species, Mycoplasma pneumoniae), Chlamydial.

Fungal Parasitic (Trichomonas species, Toxoplasma gondii), Viral (especially Herpes simplex) Drug reactions , most commonly to: Antibiotics (including, sulphonamides, penicillin),

anticonvulsants (phenytoin, barbiturates), aspirin, antituberculoids, and allopurinol and many others.

Physical factors - Radiotherapy, cold, sunlight Others - Collagen diseases, vasculitides, non-Hodgkin lymphoma, leukaemia, multiple

myeloma, myeloid metaplasia, polycythemia

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EM minor is regarded as being triggered by HSV in almost all cases.[5] A herpetic aetiology also accounts for 55% of cases of EM major.[6] Among the other infections,Mycoplasma infection appears to be a common cause.

Herpes simplex virus suppression and even prophylaxis (with acyclovir) has been shown to prevent recurrent erythema multiforme eruption.[7] The human form of orf can also cause erythema multiforme.[citation needed]

Treatment[edit]

Erythema multiforme is frequently self-limiting and requires no treatment. The appropriateness of glucocorticoid therapy can be uncertain, because it is difficult to determine if the course will be a resolving one.[8]

Histology of erythema multiforme

Skin biopsy of erythema multiforme may show in the epidermis/epithelium:

apoptotic individual keratinocytes (cellular self-destructuion, earliest histological change)

hydropic degeneration of basal keratinocytes (swollen degenerating cells at the base of the

epidermis)

intercellular oedema (spongiosis)

blisters within and under the epidermis/epithelium

epithelial/epidermal necrosis – but there are no large sheets of epidermal necrosis as seen

in Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN).

Dermal changes may include:

moderate/dense perivascular lymphocytic infiltrate (inflammation) in the papillary (upper)

dermis and along the dermo-epidermal junction (DEJ)

superficial dermal oedema (swelling)

eosinophilic infiltrates (inflammation with specific allergy cells called eosinophils).

Direct immunofluorescence of erythema multiforme

Direct immunofluorescence is not specific. It may show deposition of immune proteins C3 and fibrin along the DEJ and IgM, C3 and fibrin around blood vessels.

Proposed mechanisms

Herpes simplex(HSV)-associated EM is a delayed type hypersensitivity (DTH) reaction that develops in response to infection in predisposed individuals. The process has been well studied and involves a number of steps:

1. HSV infection of keratinocytes, which may or may not result in signs of clinical infection.

2. CD34+ cells (Langerhans precursor cells) transport HSV DNA fragments to distant

keratinocytes.

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3. HSV gene fragments are expressed in these distant keratinocytes. HSV DNA and HSV-

encoded proteins can be detected in EM-affected epidermis. However HSV virus cannot be

cultured.

4. HSV-encoded proteins recruit HSV-specific CD4+ T helper cells.

5. CD4+ T cells react to the HSV antigens by producing gamma-interferon.

6. Gamma-interferon initiates an inflammatory cascade resulting in the skin eruption of EM.

Drug-induced EM involves a different mechanism with elevated tumour necrosis factor alpha rather than gamma-interferon and CD8+ cells and not CD4+ T helper cells.

Why is EM major now considered to be distinct from SJS/TEN?

EM major can usually be distinguished from SJS/TEN on a number of clinical criteria:.

1. Type of skin lesion – the predominant skin lesion of EM is the typical and atypical target

papules and plaques and not macules which develop into sheets of skin detachment as

seen in SJS/TEN. Skin detachment of more than 1% of the body surface area is common in

SJS/TEN but uncommon in EM.

2. Distribution of the skin lesions – in EM the lesions are predominantly acrally distributed, i.e.,

begin on hands and feet. In SJS/TEN the eruption begins on the trunk.

3. Mucosal involvement – although in EM major more than two mucous membranes can be

affected, this is less common in EM and is milder (lesser severity and extent) compared to

SJS/TEN.

4. Systemic symptoms, e.g. fever, are absent or mild in EM but are prominent in SJS/TEN,

especially in the prodromal period. Fever, when present in EM, is mild (<38.5C) compared

to high fevers with SJS/TEN. Patients with SJS/TEN are systemically ill.

5. Outcome and prognosis – virtually all patients with EM recover with no sequelae. SJS/TEN

has significant morbidity and mortality.

6. Recurrences – EM can recur frequently whereas recurrence is rare in SJS/TEN.

In addition, EM is predominantly a disease of young adults (median age 24 years), especially males, whereas SJS/TEN typically affects an older population (median age 45 years).

Other points of distinction.

1. Skin biopsy histology – in EM there is more dermal inflammation and individual keratinocyte

necrosis compared to SJS/TEN which shows minimal inflammation and sheets of epidermal

necrosis.

2. Triggers – EM is triggered by an infection in the majority of cases compared to SJS/TEN

which is predominantly caused by drugs.

3. Associations – EM is not associated with HIV, cancer and collagen vascular disease as

reported with SJS/TEN. Tissue type marker associations are different.

4. Mechanisms – EM involves CD4+ T cells and gamma-interferon whereas SJS/TEN involves

Fas ligand, tumour necrosis factor alpha and CD8+ cells.

In the majority of cases, EM can be diagnosed as a distinct entity from SJS/TEN although there remain some patients in whom the distinction is not so clearcut.

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Herpes simplexFrom Wikipedia, the free encyclopedia

"Herpes" redirects here. For the virus that causes herpes simplex, see Herpes simplex virus. For all types of herpes viruses, see Herpesviridae.

Herpes simplex

Classification and external resources

Herpes labialis of the lower lip. Note the blisters in a group marked by

an arrow.

Herpes simplex (Greek: ἕρπης herpēs, "creeping" or "latent") is a viral disease from the herpesviridae family caused by bothHerpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever blisters, is an infection of the face or mouth. Oral herpes is the most common form of infection. Genital herpes, known simply as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes, cerebral herpes infection encephalitis, Mollaret's meningitis, neonatal herpes, and possibly Bell's palsy are all caused by herpes simplex viruses.

Herpes viruses cycle between periods of active disease—presenting as blisters containing infectious virus particles—that last 2–21 days, followed by a remission period. Genital herpes, however, is often asymptomatic, though viral shedding may still occur. After initial infection, the viruses are transported along sensory nerves to the sensory nerve cell bodies, where they become latent and reside lifelong. Causes of recurrence are uncertain, though some potential triggers have been identified, including immunosuppressant drugs. The previously latent virus then multiplies new virus particles in the nerve cell and these are transported along the axon of each neuron to the nerve terminals in the skin, where they are released. Over time, episodes of active disease reduce in frequency and severity.

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Herpes simplex is most easily transmitted by direct contact with a lesion or the body fluid of an infected individual.[1] Transmission may also occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are the most reliable method of preventing transmission of herpes, but they merely reduce rather than eliminate risk. Oral herpes is easily diagnosed if the patient presents with visible sores or ulcers. Early stages of orofacial herpes and genital herpes are harder to diagnose; laboratory testing is usually required.

A cure for herpes has not yet been developed. Once infected, the virus remains in the body for life. Recurrent infections (outbreaks) may occur from time to time, especially in times of immune impairment such as HIV and cancer-related immune suppression.[2] However, after several years, outbreaks become less severe and more sporadic, and some people will become perpetually asymptomatic and will no longer experience outbreaks, though they may still be contagious to others. Treatments with antivirals can reduce viral shedding and alleviate the severity of symptomatic episodes. It should not be confused with conditions caused by other viruses in the herpesviridae family such as herpes zoster, which is caused by varicella zoster virus. The differential diagnosis includes hand, foot and mouth disease due to similar lesions on the skin.

ClassificationHerpes simplex is divided into two types: HSV type 1 and HSV type 2. HSV1 causes primarily mouth, throat, face, eye, and central nervous system infections, whereas HSV2 causes primarily anogenital infections. However, each may cause infections in all areas.[3]

Signs and symptomsHSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect the face and mouth (orofacial herpes), genitalia (genital herpes), or hands (herpetic whitlow). More serious disorders occur when the virus infects and damages the eye (herpes keratitis), or invades the central nervous system, damaging the brain (herpes encephalitis). People with immature or suppressed immune systems, such as newborns, transplant recipients, or people with AIDS are prone to severe complications from HSV infections. HSV infection has also been associated with cognitive deficits of bipolar disorder,[4] and Alzheimer's disease, although this is often dependent on the genetics of the infected person.

In all cases HSV is never removed from the body by the immune system. Following a primary infection, the virus enters the nerves at the site of primary infection, migrates to thecell body of the neuron, and becomes latent in the ganglion.[5] As a result of primary infection, the body produces antibodies to the particular type of HSV involved, preventing a subsequent infection of that type at a different site. In HSV-1 infected individuals, seroconversion after an oral infection will prevent additional HSV-1 infections such as whitlow,genital herpes, and herpes of the eye. Prior HSV-1 seroconversion seems to reduce the symptoms of a later HSV-2 infection, although HSV-2 can still be contracted.

Many people infected with HSV-2 display no physical symptoms—individuals with no symptoms are described as asymptomatic or as having subclinical herpes.[6]

Condition Description Illustration

Herpetic gingivostomatitis

Herpetic gingivostomatitis is often the initial presentation during the first herpes infection. It is of greater severity than herpes labialis, which is often the subsequent presentations.

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Herpes labialisInfection occurs when the virus comes into contact with oral mucosa or abraded skin.

Herpes genitalis

When symptomatic, the typical manifestation of a primary HSV-1 or HSV-2 genital infection is clusters of inflamed papules and vesicleson the outer surface of the genitals resembling cold sores.

Herpetic whitlowand Herpes gladiatorum

Herpes whitlow is a painful infection that typically affects the fingers or thumbs. On occasion, infection occurs on the toes or on the nail cuticle. Individuals that participate in contact sports such as wrestling, rugby, and football(soccer) sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler’s herpes, or mat herpes, which presents as skin ulceration on the face, ears, and neck. Symptoms include fever, headache, sore throat and swollen glands. It occasionally affects the eyes or eyelids.

Herpesviral encephalitis andherpesviral meningitis

A herpetic infection of the brain that is thought to be caused by the retrograde transmission of virus from a peripheral site on the face following HSV-1 reactivation, along the trigeminal nerve axon, to the brain. HSV is the most common cause of viral encephalitis. When infecting the brain, the virus shows a preference for the temporal lobe.[7] HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis.

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Herpes esophagitis

Symptoms may include painful swallowing (odynophagia) and difficulty swallowing (dysphagia). It is often associated with impaired immune function (e.g. HIV/AIDS, immunosuppression in solid organ transplants).

Other

Neonatal herpes simplex is a HSV infection in an infant. It is a rare but serious condition, usually caused by vertical transmission of HSV (type 1 or 2) from mother to newborn. During immunodeficiency herpes simplex can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut.[8] Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.[9]:369 Eczema herpeticum is an infection with herpesvirus in patients with chronic atopic dermatitis may result in spread of herpes simples throughout the eczematous areas.[9]:373

Herpetic keratoconjunctivitis is a primary infection typically presents as swelling of the conjunctiva and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the cornea.

Bell's palsy

Although the exact cause of Bell's palsy, a type of facial paralysis, is unknown it may be related to reactivation of herpes simplex virus type 1.[10] This theory has been contested, however, since HSV is detected in large numbers of individuals having never experienced facial paralysis, and higher levels of antibodies for HSV are not found in HSV-infected individuals with Bell's palsy compared to those without.[11] Regardless antivirals have been found to not improve outcomes.[12]

Alzheimer's disease

HSV-1 has been proposed as a possible cause of Alzheimer's disease.[13][14] In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer's disease.[15][16]

Pathophysiology

Herpes Shedding[17]

HSV-2 genital

15–25% of days

HSV-1 oral 6–33% of days

HSV-1 genital

5% of days

HSV-2 oral 1% of days

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Herpes is contracted through direct contact with an active lesion or body fluid of an infected person.[18] Herpes transmission occurs between discordant partners; a person with a history of infection (HSV seropositive) can pass the virus to an HSV seronegative person. Herpes simplex virus 2 is typically contracted through direct skin-to-skin contact with an infected individual but can also be contacted via exposure to infected saliva, semen, vaginal fluid or the fluid from herpetic blisters.[19] To infect a new individual, HSV travels through tiny breaks in the skin or mucous membranes in the mouth or genital areas. Even microscopic abrasions on mucous membranes are sufficient to allow viral entry.

HSV asymptomatic shedding occurs at some time in most individuals infected with herpes. It can occur more than a week before or after a symptomatic recurrence in 50% of cases.[20] Virus enters into susceptible cells via entry receptors[21] such as nectin-1, HVEM and 3-O sulfated heparan sulfate.[22] Infected people that show no visible symptoms may still shed and transmit virus through their skin; asymptomatic shedding may represent the most common form of HSV-2 transmission.[20] Asymptomatic shedding is more frequent within the first 12 months of acquiring HSV. Concurrent infection with HIV increases the frequency and duration of asymptomatic shedding.[23] There are indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully verified; no significant differences are seen in the frequency of asymptomatic shedding when comparing persons with one to twelve annual recurrences to those with no recurrences.[20]

Antibodies that develop following an initial infection with a type of HSV prevents reinfection with the same virus type—a person with a history of orofacial infection caused by HSV-1 cannot contract herpes whitlow or a genital infection caused by HSV-1.[citation needed] In a monogamous couple, a seronegative female runs a greater than 30% per year risk of contracting an HSV infection from a seropositive male partner.[24] If an oral HSV-1 infection is contracted first, seroconversion will have occurred after 6 weeks to provide protective antibodies against a future genital HSV-1 infection. Herpes simplex is a double stranded DNA virus.[25]

DiagnosisPrimary orofacial herpes is readily identified by clinical examination of persons with no previous history of lesions and contact with an individual with known HSV-1 infection. The appearance and distribution of sores in these individuals typically presents as multiple, round, superficial oral ulcers, accompanied by acute gingivitis.[26] Adults with non-typical presentation are more difficult to diagnose. Prodromal symptoms that occur before the appearance of herpetic lesions help differentiate HSV symptoms from the similar symptoms of other disorders, such as allergic stomatitis. When lesions do not appear inside the mouth, primary orofacial herpes is sometimes mistaken for impetigo, a bacterial infection. Common mouth ulcers (aphthous ulcer) also resemble intraoral herpes, but do not present a vesicular stage.[26]

Genital herpes can be more difficult to diagnose than oral herpes, since most HSV-2-infected persons have no classical symptoms.[26] Further confusing diagnosis, several other conditions resemble genital herpes, including fungal infection, lichen planus, atopic dermatitis, and urethritis.[26] Laboratory testing is often used to confirm a diagnosis of genital herpes.

Laboratory tests include: culture of the virus, direct fluorescent antibody (DFA) studies to detect virus, skin biopsy, and polymerase chain reaction (PCR) to test for presence of viral DNA. Although these procedures produce highly sensitive and specific diagnoses, their high costs and time constraints discourage their regular use in clinical practice.[26]

Until recently, serological tests for antibodies to HSV were rarely useful to diagnosis and not routinely used in clinical practice.[26] The older IgM serologic assay could not differentiate between antibodies generated in response to HSV-1 or HSV-2 infection. However, the new Immunodot glycoprotein G-specific (IgG) HSV test is more than 98% specific at discriminating HSV-1 from HSV-2.[27] It is the opinion of some modern medical professionals that the new IgG test should always be clinically preferred to the old IgM test, however not all doctors appear to be informed of the availability of the newer, reliable IgG test

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Differential Diagnoses Candidiasis Chancroid Hand-Foot-and-Mouth Disease Herpes Zoster Syphilis

ManagementThere is no method to eradicate herpes virus from the body, but antiviral medications can reduce

the frequency, duration, and severity of outbreaks. Analgesics such

as ibuprofenand paracetamol(acetaminophen) can reduce pain and fever. Topical anesthetic

treatments such as prilocaine, lidocaine, benzocaine or tetracaine can also relieve itching and

pain.[46][47][48]

Antiviral

There are several antivirals that are effective for treating herpes

including: aciclovir (acyclovir), valaciclovir (valacyclovir), famciclovir, andpenciclovir. Aciclovir was

the first discovered and is now available in generic.[49] Valacyclovir is also available as a generic.[50]

Evidence supports the use of aciclovir and valaciclovir in the treatment of herpes labialis[51] as

well as herpes infections in people withcancer.[52] The evidence to support the use of acyclovir in

primary herpetic gingivostomatitis is less strong.[53]

Topical

A number of topical antivirals are effective for herpes labialis including acyclovir, penciclovir,

and docosanol.[51][54]

Alternative medicine

Certain dietary supplements and alternative remedies are claimed to be beneficial in the

treatment of herpes.[55] There is however insufficient evidence to support use of many of these

compounds including echinacea, eleuthero, L-lysine, zinc, monolaurin bee products and aloe

vera.[56] While there are a number of small studies showing possible benefit from monolaurin, L-

lysine, aspirin, lemon balm, topical zinc or licorice root cream in treatment, these are preliminary

studies that have not been confirmed by higher quality randomized controlled studies.[57]

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Herpetic gingivostomatitisFrom Wikipedia, the free encyclopedia

Gingivostomatitis

Classification and external resources

Gingivostomatitis (also known as primary herpetic gingivostomatitis or orolabial herpes) is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva.[1] Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.[2]

Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent pattern of primary herpes simplex virus (HSV) infection, since the vast majority of other primary infections are symptomless. PHGS is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. The disease presents as numerous pin-head vesicles, which rupture rapidly to form painful irregular ulcerations covered by yellow–grey membranes. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings.[3]

Clinical features

•It is usually seen between the ages of 6 months and 6 years.

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• The onset of the disease is abrupt, and is clinically characterized by high fever, headache, malaise, anorexia, irritability, bilateral sensitive regional lymphadenopathy, and sore mouthlesions.

• The affected mucosa is red and edematous, with numerous coalescing vesicles, which rapidly rupture, leaving painful small, round, shallow ulcers covered by yellow fibrin (Figs.).

•New lesions continue to develop during the first three to five days.

•The ulcers heal in 10–14 days. Both the movable and nonmovable oral mucosa may be affected.

•Gingival lesions are almost always present, resulting in enlargement and edematous and painful erosions.

•The diagnosis is usually made on clinical grounds.

Laboratory tests

•Smear,

•biopsy,

•serological tests.

Differential diagnosis

•Aphthous ulcers,

•hand-foot-and-mouth disease,

•herpangina,

•acute necrotizing ulcerative gingivitis,

•erythema multiforme,

•early pemphigus,

•desquamative gingivitis.

Treatment

•Symptomatic. In severe cases, systemic aciclovir or valaciclovir.

Aphthous stomatitisFrom Wikipedia, the free encyclopedia

Aphthous stomatitis

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Classification and external resources

Canker sore on the lower lip

Aphthous stomatitis (also termed canker sores,[1] recurrent aphthous stomatitis, RAS, recurring oral aphthae andrecurrent aphthous ulceration) is a common cause of benign and non-contagious mouth ulcers, (also called canker sores or aphthae). This condition is characterized by the repeated formation of ulcers in the mouth, in otherwise healthy individuals.[2] These ulcers occur periodically and heal completely between attacks. Symptoms range from a minor nuisance to interfering with eating and drinking, and more severe forms may be debilitating.

The cause is not completely understood, but the condition involves a T cell-mediated immune response which is triggered by a variety of factors. Individuals vary in their observed triggers, which may include nutritional deficiencies, local trauma, stress, hormonal influences, allergies, a genetic predisposition and other factors.

The condition is very common, affecting about 20% of the general population to some degree.[3]

[4] Most aphthae appear on the non-keratinizing epithelial surfaces in the mouth (i.e. anywhere except the attached gingiva, the hard palate and the dorsum of thetongue), although the more severe forms may also involve keratinizing epithelial surfaces. In the majority of cases, the individual ulcers last about 7–10 days,[2] and ulceration episodes occur about 3–6 times per year.[5] Aphthous stomatitis often starts during childhood or adolescence, and the condition usually lasts for several years before gradually disappearing.[6] There is no cure, and treatments aim to manage pain, promote healing and reduce the frequency of episodes of ulceration.[

Signs and symptoms[edit]

Aphthous ulcers on the labial mucosa (lower lip is retracted). Note erythematous "halo" surrounding ulcer.

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Persons with aphthous stomatitis have no detectable systemic symptoms or signs (i.e., outside

the mouth).[6] Generally, symptoms may include prodromal sensations such as burning, itching, or

stinging, which may precede the appearance of any lesion by some hours; and pain, which is

often out of proportion to the extent of the ulceration and is worsened by physical contact,

especially with certain foods and drinks (e.g., acidic). Pain is worst in the days immediately

following the initial formation of the ulcer, and then recedes as healing progresses.[7] If there are

lesions on the tongue, speaking and chewing can be uncomfortable, and ulcers on the soft

palate, oropharynx, or esophagus can cause odynophagia (painful swallowing).[7] Signs are

limited to the lesions themselves.

Severe disease, characterized by virtually constant ulceration (new lesions developing before old

ones have healed), may cause debilitating chronic pain and interfere with comfortable eating. In

severe cases, this prevents adequate nutrient intake, leading tomalnutrition and weight loss.[7]

Aphthous ulcers typically begin as erythematous macules (reddened, flat area of mucosa) which

develop into ulcers that are covered with a yellow-grey fibrinous membrane that can be scraped

away. An erythematous "halo" surrounds the ulcer.[3] The size, number, location, healing time,

and periodicity between episodes of ulcer formation are all dependent upon the subtype of

aphthous stomatitis.

Causes[edit]

The cause is not entirely clear,[6] but is thought to be multifactorial.[2] It has even been suggested

that aphthous stomatitis is not a single entity but rather a group of conditions with different

causes.[6] Multiple research studies have attempted to identify a causative organism, but

aphthous stomatitis appears to be non-contagious, non-infectious and not sexually transmissible.[6] The mucosal destruction is thought to be the result of a T cell (T lymphocyte) mediated immune

response which involves the generation of interleukinsand tumor necrosis factor alpha (TNF-α).[2] Mast cells and macrophages are also involved, secreting TNF-α along with the T cells. When

early aphthous ulcers are biopsied, thehistologic appearance shows a dense inflammatory

infiltrate, 80% of which is made up of T cells.[3] Persons with aphthous stomatitis have circulating

lymphocytes which react withpeptides 91–105 of heat shock protein 65-60.[6] Furthermore, the

ratio of CD4+ T cells to CD8+ T cells in the peripheral blood of individuals with aphthous

stomatitis is decreased.[3]

Despite this preferred theory of immuno-dysregulation held by most researchers,[1] aphthous

stomatitis behaves dis-similarly to autoimmune diseases in many regards. There is no association

between aphthous stomatitis and other autoimmune diseases, which often accompany each

other; common autoantibodies are not detected, the condition tends to resolve spontaneously

with advancing age rather than worsen,[6] and usually serum immunoglobulins are at normal

levels.[6]

Evidence for the T cell-mediated mechanism of mucosal destruction is strong, but the exact

triggers for this process are unknown and are thought to be multiple and varied from one person

to the next. This suggests that there are a number of possible triggers, each of which is capable

of producing the disease in different subgroups. In other words, different subgroups of individuals

with aphthous stomatitis appear to have different causes for the condition. These sub-groups

have been considered to be in three general groups, namely primary immuno-dysregulation,

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decrease of the mucosal barrier and states of heightened antigenic sensitivity.[1][3] Etiologic factors

in aphthous stomatitis are also sometimes considered in 2 categories, host-related or

environmental.

Diagnosis[edit]

Diagnosis is mostly based on the clinical appearance and the medical history.[6] The most

important diagnostic feature is a history of recurrent, self healing ulcers at fairly regular intervals.[18] Although there are many causes of oral ulceration, recurrent oral ulceration has relatively few

causes, most commonly aphthous stomatitis, but rarely Behçet's disease, erythema multiforme,

ulceration associated with gastrointestinal disease,[9][18] and recurrent intra-oral herpes simplex

infection. A systemic cause is more likely in adults who suddenly develop recurrent oral ulceration

with no prior history.[15]

Special investigations may be indicated to rule out other causes of oral ulceration. These

include blood tests to exclude anemia, deficiencies of iron, folate or vitamin B12 or celiac disease.[4] However, the nutritional deficiencies may be latent and the peripheral blood picture may appear

relatively normal.[4] Some suggest that screening for celiac disease should form part of the routine

work up for individuals complaining of recurrent oral ulceration.[8] Many of the systemic diseases

cause other symptoms apart from oral ulceration, which is in contrast to aphthous stomatitis

where there is isolated oral ulceration. Patch testing may be indicated if allergies are suspected

(e.g. a strong relationship between certain foods and episodes of ulceration). Several drugs can

cause oral ulceration (e.g. nicorandil), and a trial substitution to another drug may highlight a

causal relationship.[6]

Tissue biopsy is not usually required, unless to rule out other suspected conditions such as

oral squamous cell carcinoma.[18] Thehistopathologic appearance is not pathognomonic (the

microscopic appearance is not specific to the condition). Early lesions have a central zone of

ulceration covered by a fibrinous membrane. In the connective tissue deep to the ulcer there is

increased vascularity and a mixed inflammatory infiltrate composed of

lymphocytes, histiocytes and polymorphonuclear leukocytes. The epithelium on the margins of

the ulcer shows spongiosis and there are many mononuclear cells in the basal third. There are

also lymphocytes and histiocytes in the connective tissue surrounding deeper blood vessels near

to the ulcer, described histologically as "perivascular cuffing".[3][18]

Classification[edit]

Aphthous stomatitis has been classified as a type of non-infectious stomatitis (inflammation of the

mouth).[18] One classification distinguishes "common simple aphthae", accounting for 95% of

cases, with 3–6 attacks per year, rapid healing, minimal pain and restriction of ulceration to the

mouth; and "complex aphthae", accounting for 5% of cases, where ulcers may be present on the

genital mucosa in addition to mouth, healing is slower and pain is more severe.[5] A more common

method of classifying aphthous stomatitis is into three variants, distinguished by the size, number

and location of the lesions, the healing time of individual ulcers and whether a scar is left after

healing (see below).

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Minor aphthous ulceration[edit]

This is the most common type of aphthous stomatitis, accounting for about 80-85% of all cases.[4] This subtype is termed minor aphthous ulceration (MiAU),[6] or minor recurrent aphthous

stomatitis (MiRAS). The lesions themselves may be referred to as minor aphthae or minor

aphthous ulcers. These lesions are generally less than 10 mm in diameter (usually about 2-

3 mm),[4] and affect non-keratinized mucosal surfaces (i.e. the labial and buccal

mucosa, lateral borders of the tongue and the floor of the mouth). Usually several ulcers appear

at the same time, but single ulcers are possible. Healing usually takes seven to ten days and

leaves no scar. Between episodes of ulceration, there is usually an ulcer-free period of variable

length.[2]

Major aphthous ulceration[edit]

This subtype makes up about 10% of all cases of aphthous stomatitis.[3] It is termed major

aphthous ulceration (MaAU) or major recurrent aphthous stomatitis (MaRAS). Major aphthous

ulcers (major aphthae) are similar to minor aphthous ulcers, but are more than 10 mm in diameter

and the ulceration is deeper.[2][3] Because the lesions are larger, healing takes longer (about

twenty to thirty days), and may leave scars. Each episode of ulceration usually produces a

greater number of ulcers, and the time between attacks is less than seen in minor aphthous

stomatitis.[3] Major aphthous ulceration usually affects non keratinized mucosal surfaces, but less

commonly keratinized mucosa may also be involved, such as the dorsum (top surface) of

the tongue or the gingiva (gums).[8] The soft palate or the fauces (back of the throat) may also be

involved,[8] the latter being part of the oropharynx rather than the oral cavity. Compared to minor

aphthous ulceration, major aphthae tend to have an irregular outline.[4]

Herpetiform ulceration[edit]

Herpetiform ulcers,[2] (also termed stomatitis herpetiformis,[19] or herpes-like ulcerations) is a

subtype of aphthous stomatitis so named because the lesions resemble a primary infection

with herpes simplex virus (primary herpetic gingivostomatitis).[3] However, herpetiform ulceration

is not caused by herpes viruses. As with all types of aphthous stomatitis, it is not contagious.

Unlike true herpetic ulcers, herpetiforme ulcers are not preceded by vesicles (small, fluid filled

blisters).[8] Herpetiforme ulcers are less than 1 mm in diameter and occur in variably sized crops

up to one hundred at a time. Adjacent ulcers may merge to form larger, continuous areas of

ulceration. Healing occurs within fifteen days without scarring.[4] The ulceration may affect

keratinized mucosal surfaces in addition to non keratinized. Herpetiform ulceration is often

extremely painful, and the lesions recur more frequently than minor or major aphthous ulcers.

Recurrence may be so frequent that ulceration is virtually continuous. It generally occurs in a

slightly older age group than the other subtypes,[8] and females are affected slightly more

frequently than males.[6]

Herpetiform aphthous

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Herpetiform aphthous ulcers comprise perhaps 7%-10% of aphthous ulcers.[5] They also differ from common canker sores in many ways. Most often located in the posterior mouth, they are present in large crops of 10-150 simultaneous lesions. They are the smallest of the aphthous ulcers, being pinpoints of only about 1-3 mm in diameter with necrotic, yellow centers.[4] Lesions may be clustered together or scattered throughout the oral soft tissues.[3] They often coalesce to form a large lesion with irregular borders that resembles intraoral herpes in appearance. Women experience herpetiform aphthous ulcers more commonly than men do. Also, the lesions manifest at a later age than with other aphthae.[3] Duration of the ulcers is usually 7-14 days, although some may persist for three to five weeks. Due to the name, the lesions are often confused with herpes in etiology, leading to the alternative name "clusterform aphthous stomatitis."[4]Patients with herpetiform aphthous ulcers need to be referred for evaluation and treatment.

RAS type ulceration[edit]

Recurrent oral ulceration associated with systemic conditions is termed "RAS type ulceration",

"RAS like ulceration" or "aphthous-like ulcers".[6] Aphthous stomatitis occurs in individuals with no

associated systemic disease.[2] Persons with certain systemic diseases may be prone to oral

ulceration, but this is secondary to the underlying medical condition (see the systemic

disease section).[2] This kind of ulceration is considered by some to be separate from true

aphthous stomatitis.[2][14] However, this definition is not strictly applied. For example, many

sources refer to oral ulceration caused by anemia and/or nutritional deficiencies as aphthous

stomatitis, and some also consider Behçet's disease to be a variant.[3][4]

Treatment[edit]

The vast majority of people with aphthous stomatitis have minor symptoms and do not require

any specific therapy. The pain is often tolerable with simple dietary modification during an

episode of ulceration such as avoiding spicy or acidic foods and beverages.[7] Many

different topical and systemic medications have been proposed (see table), sometimes showing

little or no evidence of efficacy when formally investigated.[2] Some of the results of interventions

for RAS may in truth represent a placebo effect.[15] No therapy is curative, with treatment aiming

to relieve pain, promote healing and reduce the frequency of episodes of ulceration

The first line therapy for aphthous stomatitis is topical agents rather than systemic medication.[2] Topical corticosteroids are the mainstay treatment for aphthous stomatitis.[6][15]Systemic

treatment is usually reserved for severe disease due to the risk of adverse side effects associated

with many of these agents. A systematic review found that no single systemic intervention was

found to be effective.[2] Good oral hygiene is also important to prevent secondary infection of the

ulcers.[6]

Amlexanox applied topically is highly studied and effective in healing; less conclusive research

suggests that vitamin B12 supplementation and the avoidance of sodium lauryl sulfate in

toothpaste may prevent recurrence.[21]

Occasionally, in females where ulceration is correlated to the menstrual cycle or to an oral

contraceptive, progestogen or a change in oral contraceptive may be beneficial.[6] Use of nicotine

replacement therapy for people who have developed oral ulceration after stopping smoking has

also been reported.[8] Starting smoking again does not usually lessen the condition.[9] Trauma can

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be reduced by avoiding rough or sharp foodstuffs and by brushing teeth with care. If sodium

lauryl sulfate is suspected to be the cause, avoidance of products containing this chemical may

be useful. If investigations reveal deficiency states, correction of the deficiency may result in

resolution of the ulceration. Similarly patch testing may indicate that food allergy is responsible,

and the diet modified accordingly.[6]

Surgical excision of aphthous ulcers has been described, but it is an ineffective and inappropriate

treatment.[3] Silver nitrate has also been used as a chemical cauterant.[15] Apart from the

mainstream approaches detailed above, there are numerous treatments of unproven

effectiveness, ranging from herbal remedies to otherwise alternative treatments, including aloe

vera, myrtus communis, Rosa damascena, zinc sulfate, nicotine, polio

virus vaccine and prostaglandin E2

PemphigusPemphigus (/ ̍ p ɛ m f ɪ ɡ ə s /  or / p ɛ m ̍ f aɪ ɡ ə s / ) is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes.[1]

In pemphigus, autoantibodies form against desmoglein. Desmoglein forms the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes. When autoantibodies attack desmogleins, the cells become separated from each other and the epidermis becomes "unglued", a phenomenon called acantholysis. This causes blisters that slough off and turn into sores. In some cases, these blisters can cover a significant area of the skin.[2]

Types[edit]

There are several types of pemphigus which vary in severity: pemphigus vulgaris, pemphigus

foliaceus, Intraepidermal neutrophilic IgA dermatosis, and paraneoplastic pemphigus.

Pemphigus vulgaris (PV - ICD-10 L10.0) is the most common form of the disorder and

occurs when antibodies attackDesmoglein 3. Sores often originate in the mouth, making

eating difficult and uncomfortable. Although pemphigus vulgaris may occur at any age, it is

most common among people between the ages of 40 and 60. It is more frequent

among Ashkenazi Jews. Rarely, it is associated with myasthenia gravis. Nail disease may be

the only finding and has prognostic value in management.[citation needed]

Pemphigus foliaceus (PF) is the least severe of the three varieties. Desmoglein 1, the

protein that is destroyed by the autoantibody, is found in only the top dry layer of the skin. PF

is characterized by crusty sores that often begin on the scalp, and may move to the chest,

back, and face. Mouth sores do not occur. This form is also frequent among Askenazi Jews.

It is not as painful as pemphigus vulgaris, and is often mis-diagnosed

as dermatitis or eczema.

Intraepidermal neutrophilic IgA dermatosis is characterized histologically by

intraepidermal bullae with neutrophils, some eosinophils, and acantholysis.

The least common and most severe type of pemphigus is paraneoplastic

pemphigus (PNP). This disorder is a complication of cancer,

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usually lymphoma and Castleman's disease. It may precede the diagnosis of the tumor.

Painful sores appear on the mouth, lips, and the esophagus. In this variety of pemphigus, the

disease process often involves the lungs, causing bronchiolitis obliterans (constrictive

bronchiolitis). Though much less frequent, it is still found the most in the Askenazi Jewish

population. Complete removal of and/or cure of the tumor may improve the skin disease, but

lung damage is generally irreversible.

Note that Hailey-Hailey disease, also called familial benign pemphigus, is an inherited (genetic)

skin disease, not an autoimmune disease. It is therefore not considered part of the Pemphigus

group of diseases.[

Diagnosis[edit]

Pemphigus is recognized by a dermatologist from the appearance and distribution of the skin

lesions. It is also commonly diagnosed by specialists practicing otolaryngology- head and neck

surgery, periodontists, oral and maxillofacial surgeons (highly specialized surgeons with an

extensive background and qualifications in both medicine and dentistry), andeye doctors, as

lesions can affect the eyes and mucous membrane of the oral cavity. Intraorally it resembles the

more common diseases lichen planus and mucous membrane pemphigoid.[9] Definitive diagnosis

requires examination of a skin or mucous membrane biopsy by a dermatopathologist or oral

pathologist. The skin biopsy is taken from the edge of a blister, prepared for histopathology and

examined with a microscope. The pathologist looks for an intraepidermal vesicle caused by the

breaking apart of epidermal cells (acantholysis). Thus, the superficial (upper) portion of the

epidermis sloughs off, leaving the bottom layer of cells on the "floor" of the blister. This bottom

layer of cells is said to have a "tombstone appearance".

Definitive diagnosis also requires the demonstration of anti-desmoglein autoantibodies by direct

immunofluorescence on the skin biopsy. These antibodies appear as IgG deposits along

the desmosomes between epidermal cells, a pattern reminiscent of chicken wire. Anti-desmoglein

antibodies can also be detected in a blood sample using the ELISAtechnique.

Half of pemphigus patients have oral lesions alone during the first year but develop skin lesions

later.

Pemphigus vulgaris

What is pemphigus vulgaris?

Pemphigus vulgaris is a rare autoimmune disease that is characterised by blisters and erosions on the skin and mucous membranes, most commonly inside the mouth. It is the most common subtype of pemphigus, accounting for 70% of all pemphigus cases worldwide although it is extremely rare in New Zealand (about one case per million). The other two main subtypes of pemphigus are pemphigus foliaceus and paraneoplastic pemphigus.

What causes pemphigus vulgaris?

Pemphigus vulgaris is an autoimmune blistering disease, which basically means that an individual's immune system starts reacting against his or her own tissue.

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The building block cells of the epidermis are called keratinocytes. These cells are cemented together at special sticky spots called desmosomes. In pemphigus vulgaris immunoglobulin type G (IgG) autoantibodies bind to a protein called desmoglein 3, which is found in desmosomes in the keratinocytes near the bottom of the epidermis. The result is the keratinocytes separate from each other, and are replaced by fluid, the blister.

Who gets pemphigus vulgaris?

Pemphigus vulgaris affects people of all races, age and sex. It appears most commonly between the ages of 50-60 years, and is more common in Jews and Indians presumably for genetic reasons.

What are the signs and symptoms of pemphigus vulgaris?

Most patients first present with lesions on the mucous membranes such as the mouth and genitals. Several months' later blisters on the skin may develop or in some cases mucosal lesions are the only manifestation of the disease.

The most common mucosal area affected is the inside of the mouth but others include the conjunctiva, oesophagus, labia, vagina, cervix, penis, urethra and anus. Common features of oral mucosal pemphigus include:

50-70% of patients get oral lesions

blistering superficial and often appears as erosions

widespread involvement in the mouth

painful and slow to heal

may spread to the larynx causing hoarseness when talking

may make it difficult to eat or drink

Skin lesions appear as thin walled flaccid blisters filled with clear fluid that easily rupture causing painful erosions. Erosions in the skin folds may develop into vegetative lesions which are granular and crusty looking (known as pemphigus vegetans).

Pemphigus vulgaris

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Tests for pemphigus vulgaris

Diagnosis generally requires a skin biopsy, which shows typical features of rounded-up separated keratinocytes (called acantholytic cells) within the blisters just above the basal layer of the epidermis. Suprabasal clefting may be reported. See pathology of pemphigus vulgaris.

Pemphigus is confirmed by direct immunofluorescence staining of the skin biopsy sections to reveal antibodies.

In most cases, circulating antibodies can be detected by a blood test (indirect immunofluorescence test). The level of antibodies fluctuates and may reflect the effectiveness of treatment.

Treatment of pemphigus vulgaris

The primary aim of treatment is to decrease blister formation, prevent infections and promote healing of blisters and erosions. Oral corticosteroids are the mainstay of medical treatment for controlling the disease. Since their use, many deaths from pemphigus vulgaris have been prevented (mortality rate dropped from 99% to 5-15%). They are not a cure for the disease but improve the patient's quality of life by reducing disease activity. Unfortunately higher doses of corticosteroids may result in serious side effects and risks. Other immune suppressive drugs are used to minimise steroid use. These include:

Azathioprine

Cyclophosphamide

Dapsone

Tetracyclines

Nicotinamide

Plasmapheresis

Gold

Mycophenolate mofetil

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Intravenous immunoglobulin

The TNFα inhibitor, infliximab

Anti-CD20 monoclonal antibody (rituximab)

At optimal therapy patients may still continue to experience mild disease activity.

Appropriate wound care is particularly important, as this should promote healing of blisters and erosions.

Patients should minimize activities that may traumatise the skin and mucous membranes during active phases of the disease. These include activities such as contact sports and eating or drinking food that may irritate or damage the inside of the mouth (spicy, acidic, hard and crunchy foods).

Pemphigus vulgaris pathologyPemphigus vulgaris is a chronic vesiculobullous skin disorder characterised by autoantibodies against desmoglein 3, which is a component of the desmosome (an intracellular adhesion molecule). Disruption of keratinocyte adhesion leads to superficial blistering and erosion affecting the skin and/or mucous membranes.

Histology of pemphigus vulgaris

Early lesions of pemphigus vulgaris show suprabasal epidermal acantholysis, clefting and blister formation. The blister cavity may contain inflammatory cells including eosinophils and rounded acantholytic cells with intensely eosinophilic cytoplasm and a perinuclear halo. The floor of the blister may be lined with intact keratinocytes, the “tombstone pattern” (figures 1, 2). Acantholysis can also affect adnexae. Dermal changes include perivascular inflammatory infiltrate particularly with eosinophils.

Pemphigus vulgaris pathology

 

Figure 1

 

Figure 2

 

Figure 3

 

Figure 4

Special studies of pemphigus vulgaris

Direct immunofluorescence may be positive in perilesional skin with intercellular deposits of IgG and/or C3 in the epidermis (figures 3, 4). Antigen deposition can be seen in hair follicles (follicular outer root sheath and germinal matrix), meaning direct immunofluorescence may be positive when performed on plucked hair follicles.

Differential diagnosis of pemphigus vulgaris

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Darier disease: Suprabasal clefting with dyskeratosis in the form of corps ronds and grains. Immunofluorescence is negative.

Hailey-Hailey disease: Disruption of epithelium adjacent to bullae (intact in pemphigus vulgaris) with sparing of adnexal structures. Immunofluorescence is negative.

Pemphigus foliaceus: Acantholysis more superficial within the granular layer. Lacks mucous membrane involvement.

Grover Disease: There is a pemphigus-like form of this disease. Negative immunofluorescence and lack of adnexal involvement are helpful features.

Pemphigus vegetans associated with verrucous lesions

Histology of a vegetating lesion from a skin fold revealed a suprabasal cleft with acantholytic cells; from a verrucous acral lesion, epithelial hyperplasia with microabscesses composed of eosinophils, neutrophils, and some acantholytic cells (Figure 4). The first histologic examination of the oral lesion was reviewed, and a suprabasal cleft was found (Figure 4)

Historically, cases of pemphigus vegetans have been divided into 2 clinical subclasses: the Hallopeau type and the Neumann type. The first starts with circumscribed pustules and has a relatively benign course; in contrast, the Neumann type has vesicles and bullae as primary lesions, is usually more frequently seen and develops extensive lesions that are often refractory to therapy.5 The diagnosis of pemphigus vegetans is based on clinical manifestations and confirmed by histology. Involvement of the vermillion border of the lips is the clinical hallmark of oral involvement. Proliferative growth begins at the sites of pustules or bullae that erode, and it gradually becomes vegetative and hypertrophic.6 These verrucous lesions can be clinically similar to common warts7 or they may evolve into vegetating masses up to several centimeters in diameter, with fresh vesicles or pustules at the periphery of the lesion.6 Both circumstances were present this case. Nail involvement in pemphigus is rare; it has been described in pemphigus vulgaris in a variety of manifestations: chronic paronychia, onychomadesis, onycholysis, Beau's lines, trachyonychia, subunguial hemorrhage, nail dystrophy, and vegetative lesions over paronychia.7,8

Histological findings, such as epithelial hyperplasia, suprabasal cleft and acantholytic cells, as well as microabscesses composed of eosinophils and neutrophils, are the main characteristics, as seen in this patient.6,9

Immunofluorescence techniques have proved to be important in the differential diagnosis of bullous disorders and the pemphigus group has the classical intercellular pattern.

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Herpes zoster

Herpes zoster

Classification and external resources

Herpes zoster blisters on the neck and shoulder

Herpes zoster (or simply zoster), commonly known as shingles and also known as zona, is a viral disease characterized by apainful skin rash with blisters in a limited area on one side of the body (left or right), often in a stripe. The initial infection with varicella zoster virus (VZV) causes the acute, short-lived illness chickenpox which generally occurs in children and young adults. Once an episode of chickenpox has resolved, the virus is not eliminated from the body and can go on to cause herpes zoster often many years after the initial infection. Herpes zoster is not the same disease as herpes simplex, despite the name similarity; both the varicella zoster virus and herpes simplex virus belong to the same viral subfamily Alphaherpesvirinae.

After the initial episode of chickenpox resolves, the varicella zoster virus remains latent in the nerve cell bodies and, less frequently, the non-neuronal satellite cells of the dorsal root, cranial nerve or autonomic ganglia,[1] without causing any symptoms.[2] Years or decades after the initial infection, the virus may break out of nerve cell bodies and travel down nerve axons to cause viral infection of the skin in the region of the nerve. The virus may spread from one or more ganglia along nerves of an affected segment and infect the corresponding dermatome (an area of skin supplied by one spinal nerve) causing a painful rash.[3]

[4] Although the rash usually heals within two to four weeks, some sufferers experience residual nerve pain for months or years, a condition called postherpetic neuralgia. Exactly how the virus remains latent in the body, and subsequently re-activates, is not understood.

The zoster (shingles) vaccine is considered the most effective way to reduce incidence of herpes zoster and postherpetic neuralgia, and to reduce severity of any outbreak. Antiviral drug treatment is considered a second-line approach, but can reduce the severity and duration of herpes zoster if a seven- to ten-day course of these drugs is started within 72 hours of the

appearance of the characteristic rash.

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Signs and symptoms[edit]

A case of shingles that demonstrates the typical dermatomal distribution, in this case C8/T1

The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are

nonspecific, and may result in an incorrect diagnosis.[5][11] These symptoms are commonly

followed by sensations of burning pain, itching, hyperesthesia (oversensitivity),

orparesthesia ("pins and needles": tingling, pricking, or numbness).[12] The pain may be mild to

extreme in the affected dermatome, with sensations that are often described as stinging, tingling,

aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain.[13]

Herpes zoster in children is often painless, but older people are more likely to get zoster as they

age, and the disease tends to be more severe.[14]

In most cases after one to two days, but sometimes as long as three weeks, the initial phase is

followed by the appearance of the characteristic skin rash. The pain and rash most commonly

occurs on the torso, but can appear on the face, eyes or other parts of the body. At first the rash

appears similar to the first appearance of hives; however, unlike hives, herpes zoster causes skin

changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to

one side of the body and does not cross the midline.[12] Zoster sine herpete ("zoster without

herpes") describes a patient who has all of the symptoms of herpes zoster except this

characteristic rash.[15]

Later the rash becomes vesicular, forming small blisters filled with a serous exudate, as the fever

and general malaise continue. The painful vesicles eventually become cloudy or darkened as

they fill with blood, and crust over within seven to ten days; usually the crusts fall off and the skin

heals, but sometimes, after severe blistering, scarring and discolored skin remain.[12]

Postherpetic neuralgiaPostherpetic neuralgia is a nerve pain due to damage caused by the varicella zoster virus. Typically, the neuralgia is confined to adermatomic area of the skin and follows an outbreak of herpes zoster (commonly known as shingles) in that same dermatomic area. The neuralgia typically begins when the herpes zoster vesicles have crusted over and begun to heal, but it can begin in the absence of herpes zoster, in which case zoster sine herpete is presumed (see Herpes zoster).

Treatment options for postherpetic neuralgia include antidepressants, anticonvulsants (such as gabapentin, pregabalin, ortopiramate), gabapentin enacarbil (a prodrug of gabapentin) and topical agents such as lidocaine patches or capsaicin lotion. Opioid analgesics may also be appropriate in many situations. There are some sporadically successful experimental treatments, such as rhizotomy (severing or damaging the affected nerve to relieve pain) and TENS (a type of electrical pulse therapy).

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Predisposing factors[edit]

Race: It may influence susceptibility to herpes zoster. African Americans are one fourth as

likely as Caucasians to develop this condition.

Often an older, debilitated or immune compromised population.

Signs and symptoms[edit]

Symptoms:

With resolution of the herpes zoster eruption, pain that continues for three months or more is

defined as postherpetic neuralgia.

Pain is variable, from discomfort to very severe, and may be described as burning, stabbing,

or gnawing.

Signs:

Area of previous herpes zoster may show evidence of cutaneous scarring.

Sensation may be altered over the areas involved, in the form of either hypersensitivity or

decreased sensation.

In rare cases, the patient might also experience muscle weakness, tremor, or paralysis if the

nerves involved also control muscle movement.

Treatment[edit]

Treatment for postherpetic neuralgia depends on the type and characteristics of pain experienced

by the patient. Pain control is essential to quality patient care; it ensures patient comfort. Possible

options include:

Antiviral  agents, such as famciclovir, are given at the onset of attacks of herpes zoster to

shorten the clinical course and to help prevent complications such as postherpetic neuralgia.

However, they have no role to play following the acute attack once postherpetic neuralgia has

become established.

Analgesics Locally applied topical agents

Aspirin mixed into an appropriate solvent such as diethyl ether may reduce pain.[2]

Gallium maltolate  in a cream or ointment base has been reported to relieve refractory postherpetic neuralgia.[3]

Lidocaine  skin patches. These are small, bandage-like patches that contain the topical, pain-relieving medication lidocaine. The patches, available by prescription, must be applied directly to painful skin and deliver relief for four to 12 hours. Patches containing lidocaine can also be used on the face, taking care to avoid mucus membranes e.g., the eyes, nose and mouth.

Systemically delivered Non-opiates such as paracetamol or the non-steroidal anti-inflammatory drugs. Opioids  provide more potent pain control and the weaker members such

as codeine may be available over the counter in combination with paracetamol (co-codamol). Other opioids are prescription-only and include higher dosages of codeine, tramadol, morphine or fentanyl. Most opioids have sedating properties, which are beneficial for patients who experience pain.

Pain modification therapy

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Antidepressants . These drugs affect key brain chemicals, including serotonin and norepinephrine, that play a role in both depression and how the body interprets pain. Doctors typically prescribe antidepressants for postherpetic neuralgia in smaller doses than they do for depression. Low dosages of tricyclic antidepressants, includingamitriptyline, seem to work best for deep, aching pain. They do not eliminate the pain, but they may make it easier to tolerate. Other prescription antidepressants (e.g.,venlafaxine, bupropion and selective serotonin reuptake inhibitors) may be off-label used in postherpetic neuralgia and generally prove less effective, although they may be better tolerated than the tricyclics.

Anticonvulsants . These agents are used to manage severe muscle spasms and provide sedation in neuralgia. They have central effects on pain modulation. Medications such as phenytoin (Dilantin, Phenytek), used to treat seizures, also can lessen the pain associated with postherpetic neuralgia. The medications stabilize abnormal electrical activity in the nervous system caused by injured nerves. Doctors often prescribe another anticonvulsant called carbamazepine (Carbatrol, Tegretol) for sharp, jabbing pain. Newer anticonvulsants, such as gabapentin (Neurontin) and lamotrigine (Lamictal), are generally tolerated better and can help control burning and pain.

gabapentin enacarbil  (HORIZANT), an alpha-2-delta-1 ligand and a prodrug of gabapentin, was approved by the FDA in 2012 for the management of postherpetic neuralgia.

Corticosteroids  are commonly prescribed but a Cochrane Review found limited evidence and

no benefit.[4]

Other non-pharmacological treatments for postherpetic neuralgia include the following: Acupuncture . Moxibustion . Relaxation techniques . These can include breathing exercises, visualization and

distraction. Heat therapy . Cold therapy. Cold packs can be used. Transcutaneous Electrical Nerve Stimulation . This involves the stimulation of peripheral

nerve endings by the delivery of electrical energy through the surface of the skin.[5]

Spinal cord stimulator . The electrical stimulation of the posterior spinal cord works by activating supraspinal and spinal inhibitory pain mechanisms.[6]

In some cases, treatment of postherpetic neuralgia brings complete pain relief. But most people

still experience some pain, and a few do not receive any relief. Although some people must live

with postherpetic neuralgia the rest of their lives, most people can expect the condition to

gradually disappear on its own within five years.

Herpes virus infection pathologyHerpes simplex, varicella and herpes zoster infections show identical histology. Clinical correlation or immunohistochemistry and/or viral culture or PCR (of an appropriate swab or tissue specimen) is required to differentiate these viral infections.

Histology of herpes infections

The histology of herpes infections is very distinctive. The low power pattern of a typical lesion is of an intraepidermal blister (Figure 1). The key feature is acantholysis with solitary keratinocytes within the blister cavity (Figures 1, 2, 3). Keratinocytes will show the nuclear changes of viral infection. These included margination of the nuclear chromatin, multinucleation and nuclear inclusions (Figures 3, 4, 5). The viral inclusions are small pink deposits with a clear halo seen within

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the nucleus. When present in herpes virus infection and present with the other nuclear changes of this infection they are called Cowdry Type A inclusions. Cowdry Type B inclusions are associated with other infections such as polio virus and do not have the other nuclear changes of herpes infection.

Early changes of vacuolation in the cytoplasm may be seen along the basal keratinocytes. As the cells swell and separate, the cytoplasm becomes eosinophilic, particularly notable in the multinucleated cells. The inflammatory infiltrate is mixed, predominantly lymphocytes and neutrophils with scattered eosinophils frequently seen (Figure 6).

Herpes virus infection pathology

 

Figure 1

 

Figure 2

 

Figure 3

 

Figure 4

 

Figure 5

 

Figure 6

Histological variants of herpes infections

Herpes folliculitis: Changes in this variant can be subtle and hence easily overlooked particularly in early lesions or when the follicle is only partially represented. The key finding is of a necrotic hair follicle with an associated dense superficial and deep lymphocytic infiltrate with neutrophils. Typical viral changes can be seen in acantholytic epithelial cells of predominantly the infundibular region or in involved adjacent epidermis.

Verrucous varicella and herpes zoster: In this variant there is prominent hyperkeratosis and epidermal acanthosis in addition to the viral cytopathic changes.

Special tests in herpes infections

Immunoperoxidase staining by monoclonal antibody is available to herpes simplex types 1 and 2 and to varicella zoster. It is also possible to perform PCR and/or culture an appropriate specimen to distinguish between both herpes simplex and the herpes zoster viruses.

Differential diagnosis of herpes infections

Coxsackie virus infection / hand foot and mouth disease: Blisters show intraepidermal vesiculation and acantholysis without nuclear inclusions or multinucleation.

Pemphigus vulgaris: Clinically these conditions would be rarely confused. Suprabasal acantholysis is noted with vesicle formation in advanced lesions, and small numbers of acantholytic cells are seen within this space. Viral changes are lacking. However, it should be noted that disseminated herpes

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simplex virus infection (Kaposi’s varicellifom eruption) can complicate pemphigus vulgaris. In troublesome cases immunofluorescence studies are usually decisive but if necessary the additional special studies noted above may also be used.

It is worth noting that a number of conditions have been reported to arise in the site of prior herpes zoster infection. These include chronic lymphocytic leukemia, granuloma annulare, lichen planus, keloid scarring, vasculitis, sarcoidosis, morphea, lymphoma and skin cancers. The acute changes of viral infection are usually not evident.

Acute necrotizing ulcerative gingivitis

Necrotizing ulcerative gingivitis/periodontitis

Classification and external resources

A fairly mild presentation of acute necrotizing ulcerative gingivitis at

the typical site on the gums of the lower front teeth.

Acute necrotizing ulcerative gingivitis (ANUG; colloquially known as trench mouth) is a common, non-contagious infection of the gums with sudden onset. The main features are painful, bleeding gums, and ulceration of inter-dental papillae (the sections of gum between adjacent teeth). This disease, along with necrotizing (ulcerative) periodontitis (NP or NUP) is classified as a necrotizing periodontal disease, one of the seven general types of periodontitis. The often severe gingival pain that characterizes ANUG distinguishes it from the more common chronic periodontitis which is rarely painful. ANUG is the acute presentation of necrotizing ulcerative gingivitis (NUG), which is the usual course the disease takes. If improperly treated or neglected, NUG may become chronic and/or recurrent. The causative organisms are mostly anaerobic bacteria, particularly Fusobacteria and Spirocaete species. Predisposing factors include poor oral hygiene, smoking, malnutrition, psychological stress and immunosuppression (sub-optimal functioning of the immune system). When the attachments of the teeth to the bone are involved, the term NUP is used. Treatment of ANUG is by debridement (although pain may prevent this) and antibiotics (usually metronidazole) in the acute phase, and improving oral hygiene to prevent recurrence. Although the condition has a rapid onset and is debilitating, it usually resolves quickly and does no serious harm. 

Classification[edit]

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Necrotizing gingivitis is part of a spectrum of disease termed necrotizing periodontal diseases. It

is the most minor form of this spectrum, with more advanced stages being termed necrotizing

periodontitis, necrotizing stomatitis and the most extreme, cancrum oris. Acute necrotizing

ulcerative gingivitis (ANUG) refers to the clinical onset of NUG. The word acute is used because

usually the onset is sudden.[1] Other forms of NUG may be chronic or recurrent.

Necrotizing ulcerative periodontitis (NUP) this is where the infection leads to attachment loss, and

involves only the gingiva, periodontal ligament and alveolar ligament.[1][2][3]Progression of the

disease into tissue beyond the mucogingival junction characterizises nexrotizing stomatitis.

Signs and symptoms[edit]

In the early stages some patients may complain of a feeling of tightness around the teeth.[1] Three

signs/symptoms must be present to diagnose this condition:[1]

Severe gingival pain.[4]

Profuse gingival bleeding that requires little or no provocation.[1]

Interdental papillae are ulcerated with necrotic slough.[4] The papillary necrosis of NUG has

been described as "punched out".[1]

Other signs and symptoms may be present, but not always.[1]

Oral malodor (intraoral halitosis).

Bad taste (metallic taste).[4]

Malaise, fever and/or cervical lymph node enlargement are rare (unlike the typical features

of herpetic stomatitis).[4] Pain is fairly well localized to the affected areas.[4] Systemic reactions

may be more pronounced in children.[1] Cancrum oris (noma) is a very rare complication, usually

in debilitated children.[4] Similar features but with more intense pain may be seen in necrotizing

periodontitis in HIV/AIDS.[4]

Causes[edit]

Necrotizing periodontal disease is caused by a mixed bacterial infection that

includes anaerobes such as P. intermedia[3] and Fusobacterium as well as spirochetes, such

asTreponema.[4]

ANUG may also be associated with diseases in which the immune system is compromised,

including HIV/AIDS.[2] ANUG is an opportunistic infection that occurs on a background of impaired

local or systemic host defenses. The predisposing factors for ANUG are smoking, psychological

stress, malnutrition and immunosuppression.

Zones of infection have been described. These are (superficial to deep) the bacterial zone, the

neutrophil rich zone, the necrotic zone and the spirochetal zone.

Diagnosis[edit]

Diagnosis is usually clinical.[4] Smear for fusospirochaetal bacteria and leukocytes; blood picture

occasionally.[4] The important differentiation is with acute leukaemia or herpetic stomatitis.[4]

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Epidemiology[edit]

In developed countries, this disease occurs mostly in young adults. In developing countries, NUG

may occur in children of low socioeconomic status, usually occurring with malnutrition (especially

inadequate protein intake) and shortly after the onset of viral infections (e.g. measles).[1]

Predisposing factors include smoking, viral respiratory infections and immune defects, such as in

HIV/AIDS. Uncommon, except in lower socioeconomic classes, this typically affects adolescents

and young adults, especially in institutions, armed forces, etc., or people with HIV/AIDS.[4] The

disease has occurred in epidemic-like patterns, but it is not contagious.[1]

Treatment[edit]

Treatment includes irrigation and debridement of necrotic areas (areas of dead and/or dying gum

tissue), oral hygiene instruction and the uses of mouth rinses and pain medication. If there is

systemic involvement, then oral antibiotics may be given, such as metronidazole.[4] As these

diseases are often associated with systemic medical issues, proper management of the systemic

disorders is appropriate.[2]

Prognosis[edit]

Untreated, the infection may lead to rapid destruction of the periodontium and can spread, as

necrotizing stomatitis or noma, into neighbouring tissues in the cheeks, lips or the bones of the

jaw. As stated, the condition can occur and be especially dangerous in people with weakened

immune systems. This progression to noma is possible in malnourished susceptible individuals,

with severe disfigurement possible.

Pyogenic granulomaPyogenic granuloma (also known as a "Eruptive hemangioma", "Granulation tissue-type hemangioma", "Granuloma gravidarum", "Lobular capillary hemangioma", "Pregnancy tumor", and "Tumor of pregnancy"[1][2]) is a vascular lesion that occurs on both mucosa and skin, and appears as an overgrowth of tissue due to irritation, physical trauma or hormonal factors.[3][4] It is often found to involve the gums, the skin and nasal septum, and has also been found far from the head such as in the thigh.[5]

Signs and symptoms[edit]

Clinical presentation[edit]

The appearance of pyogenic granuloma is usually a color ranging from red/pink to purple, and

can be smooth or lobulated. Younger lesions are more likely to be red because of the high

number of blood vessels. Older lesions begin to change into a pink color. Size ranges from a few

millimeters to centimeters. This is not to say that the pyogenic granuloma can not be bigger but it

is more common to see one within these measurements.[medical citation needed] It can be painful,

especially if located in an area of the body where it is constantly disturbed. Pyogenic granulomas

can grow rapidly and will often bleed profusely with little or no trauma. Some cases may also

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include the granuloma "leaking" an oil like substance causing the surface to be damp. This is

especially if the granuloma is located on the scalp.[medical citation needed]

It is most likely to occur in children and younger adults, and there is a definite gender difference

with more females affected than men. In pregnant women, it is most likely to occur in the first

trimester with an increasing incidence up until the seventh month and is often seen on the

anterior nasal septum as a source of frequent nose bleeds. Pyogenic granulomas appear on the

gingiva in 75% of cases, more often in the maxillary than mandibular jaw. Anterior areas are more

often affected than posterior areas. It can also be found on the lips, tongue, and inner cheek.

Poor oral hygiene or trauma are usually precipitating factors.

One study has suggested a correlation between pyogenic granuloma

and Bartonella seropositivity.[7] However, this association has been questioned by others.[8] The

appearance of a pyogenic granulomas microscopically has a highly vascular granulation

tissue. Inflammation is present. The lesion may have a fibrous character if it is older, and the

surface may have ulcerations. Pyogenic granuloma rarely occurs in the conjunctiva, cornea or

connective tissue of the eye following minor local trauma. Grossly these mass lesions resemble

those occurring at more common sites. The relationship of this lesion to the lobular capillary

hemangioma of skin and oropharyngeal mucosa commonly referred to as pyogenic granuloma is

uncertain.

Associated conditions[edit]

Due to its overwhelming incidence on the gingiva, the condition is often associated with two

other diseases, though not because they occur together. Instead, the three are associated with

each other because they appear frequently on gingiva - peripheral giant cell

granuloma and peripheral ossifying fibroma. However, detailed analysis can be used to

distinguish these conditions.[9]

The appearance can be very similar to that of a hemangioma but unlike hemangiomas they can

appear after birth.

Oral Neurofibroma 

Neurofibroma is an uncommon benign tumor of the oral cavity derived from the cells that constitute the nerve sheath.

Neurofibroma is seen either as a solitary lesion or as part of the generalized syndrome of neurofibromatosis (usually neurofibromatosis type 1 [NF-1], also called von Recklinghausen disease of the skin). The solitary form does not differ from the disseminated form or the multiple form of the

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disease, except that systemic and hereditary factors present in the disseminated form are absent in the solitary type. Multiple neurofibromas have also been strongly associated with the polyglandular syndrome multiple endocrine neoplasia type 3 (MEN-3).[1]

Oral cavity involvement by a solitary and peripheral plexiform neurofibroma in patients with no other signs of neurofibromatosis is uncommon. Sporadic cases have been reported in the submandibular gland, tongue, and on the periosteum at the mental foramen. This sporadic syndromic occurrence has also been seen in the cutaneous region, and several authors have suggested that these isolated neurofibromas may represent a hamartomatous growth.

HistoryPatients usually present with an uninflamed, slowly enlarging, asymptomatic lesion that varies greatly in size from tiny nodules to large pendulous masses. The lesion is rarely painful; however, patients may experience pain if the lesion is secondarily traumatized due to its location, eg, on the tongue or on the hard palate.

PhysicalOral neurofibromas usually present as submucosal, nontender, discrete masses that range in size from a few millimeters to several centimeters (see images below). The lesions are typically pedunculated or sessile, usually painless, but occasionally pain or paresthesia is reported due to nerve compression. Typically, lesions are less than 2 cm in greatest diameter. Larger lesions of up to 8 centimeters are usually seen in syndromic cases.

The tumors tend to grow slowly, and patients are usually asymptomatic.

Manifestations of neurofibromatosis specific to the oral cavity include enlarged fungiform papillae on the dorsum of the tongue and diffuse enlargement of the gingiva.

In patients with mandibular involvement, enlargement of the inferior alveolar canal in the mandible and a flaring of the inferior alveolar foramen (the so-called blunderbuss foramen) have been reported.

Oral manifestations may be seen in as many as 70% of patients with neurofibromatosis. Involvement of the trigeminal nerve may cause facial pain or paresthesia. Neurofibromatosis of the skin may present as multiple nodules or as a single pendulous mass.

CausesThe cause of these lesions is unknown; however, neurofibromatosis syndrome or the disseminated form is inherited as an autosomal dominant trait and may present with a variety of lesions, including a highly variable number of neurofibromas.

Eosinophilic ulcer of the oral mucosaFrom Wikipedia, the free encyclopedia

Eosinophilic ulcer of the oral mucosa (also known as "Eosinophilic ulcer of the tongue,"[1] "Riga–Fede disease,"[1] and "Traumatic eosinophilic granuloma"[1]) is a condition characterized by an ulcer with an indurated and elevated border.[2]:803 The lesion might be tender, fast-growing and the patient often not be aware of any trauma in the area.

Definition[edit]

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Traumatic eosinophilic granuloma of the tongue (TEGT) is a reactive condition that commonly occurs on the ventral tongue.

Causes[edit]

It is often associated with trauma. However, other causes are suspected, such as drugs, inherent predisposition, immune reaction, or lymphoproliferative disorder.

Differential Diagnosis[edit]

Squamouce Cell Carcinoma,

Pyogenic granulomas,

Lesions of a chronic granulomatous disease

Mesenchymal tumors

What is eosinophilic ulcer of the oral mucosa?

Eosinophilic ulcer of the oral mucosa is an uncommon benign ulcer seen in middle-aged to elderly adults that appears suddenly in the mouth or on the lips, is usually painful, and heals over a few weeks. It may represent a nonspecific reaction pattern to trauma.

Eosinophils are a type of inflammatory cell with a characteristic appearance under the microscope.

Eosinophilic ulcer of the oral mucosa is also known as traumatic ulcerative granuloma with stromal eosinophilia, oral traumatic granuloma, traumatic granuloma of the tongue or eosinophilic ulcer of the tongue. It is possibly the adult version of Riga-Fede disease.

Eosinophilic ulcer of the lip

Who gets eosinophilic ulcer/s of the oral mucosa, and why?

Eosinophilic ulcer of the oral mucosa affects adults, with a peak in the sixth and seventh decades of life (50-80 years old). There is a slight female predominance reported.

The cause of eosinophilic ulcer of the oral mucosa is unknown. Trauma is a reported trigger in 39%. The ulcer usually occurs on sites where trauma from teeth is common and it is seen in the age group most likely to have damaged teeth and dentures that may cause trauma. However, most simple traumatic ulcers in the mouth do not show the characteristic clinical and histological features of eosinophilic ulcer. Therefore it has been suggested that trauma may allow as-yet-

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unidentified infections, toxins or foreign proteins to enter and trigger the characteristic inflammatory reaction in susceptible people. Another theory is that is represents a CD30+ lymphoproliferative disorder (a type of lymphoma).

Clinical features of eosinophilic ulcer of the oral mucosa

The typical clinical features of eosinophilic ulcer of the oral mucosa include:

Rapid growth

Painful – in most but not all cases

Solitary – multiple or recurrent lesions are reported but are uncommon

Size range from a few mm to several cm

Base – white or yellow film which can be wiped off

Edge – raised and firm

Surrounding redness

The most commonly affected site is the tongue, usually the sides or the top.

Other reported locations (in decreasing order) are:

Inside of cheeks

Between the gum and cheek (mucobuccal fold)

Lips (usually the lower lip)

Gums

Palate

Floor of the mouth

Behind the molar teeth

The patient is generally well, but eating and drinking may be limited by pain. Enlarged lymph glands in the neck may be felt in rare cases.

Eosinophilic ulcer of the oral cavity usually heals by itself within one month, but can persist up to one year. Recurrences have rarely been reported.

Atypical clinical presentations without an ulcer have included:

Flat red patches

Erythroplakia

Oral leukoplakia

Firm swelling

How is the diagnosis of eosinophilic ulcer of the oral mucosa made?

A biopsy is usually required to confirm this diagnosis and exclude other conditions, such as aphthous ulcers and most importantly oral cancer and infections.

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The histology is characteristic:

Ulcerated mucosal surface

Poorly developed granulomas

Mixed inflammatory infiltrate extending deep into muscle and salivary glands

Numerous eosinophils – showing degranulation

Large atypical CD30+ T-cells – occasional, scattered, can be monoclonal

Increased numbers of mast cells

Degeneration and loss of muscle fibres

Treatment of eosinophilic ulcer of the oral mucosa

Eosinophilic ulcer of the oral mucosa usually heals by itself within one month, so no specific treatment is required. Rapid healing is typically seen after biopsy. Analgesics may be required for pain relief. Attention to rough teeth or dental prostheses may aid healing.

Reported treatments have included:

Surgical excision

Topical corticosteroid  – mouthwash, cream, intralesional injection, oral

Antibiotics

Simple curettage and diathermy

Radiotherapy

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Traumatic ulceration[edit]

Most mouth ulcers that are not associated with recurrent aphthous stomatitis are caused by local

trauma. The mucous membrane lining of the mouth is thinner than the skin, and easily damaged

by mechanical, thermal (heat/cold), chemical or electrical means, or by irradiation.

Mechanical[edit]

A small ulcer on the lower labial frenum.

Common causes of oral ulceration include rubbing on sharp edges of teeth, fillings, crowns, false

teeth (dentures), braces (orthodontic appliances). Accidental biting caused by a lack of

awareness of painful stimuli in the mouth (following a local anesthetic e.g. during dental

treatment) may cause ulceration which the person becomes aware of as the anesthetic wears off

and the full sensation returns. Eating rough foods (e.g. potato chips) can damage the lining of the

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mouth. Some people cause damage inside their mouths themselves, either through an absent

minded habit or as a type of deliberate self harm (factitious ulceration). Examples include biting

the cheek, tongue or lips, rubbing a finger nail, pen or tooth pick inside the mouth. Tearing (and

subsequent ulceration) of the upper labial frenum may be a sign of child abuse (non-accidental

injury).[4] Iatrogenic ulceration can also occur during dental treatment, when

incidental abrasions to the soft tissues of the mouth are common. Some dentists apply a

protective layer of petroleum jelly to the lips before carrying out dental work to minimize the

number of incidental injuries. The lingual frenum is also vulnerable to ulceration by repeated

friction during oral sexual activity, in which case the incisal edges of the mandibular teeth can be

smoothed to minimize the chance of trauma.[5]

Thermal and electrical burn[edit]

Thermal burns usually result from placing hot food or beverages in the mouth. This may occur in

those who eat or drink before a local anesthetic has worn off. The normal painful sensation is

absent and a burn may occur. Microwave ovens sometimes produce food which is cold externally

and very hot internally, and this has led to a rise in the frequency of intra-oral thermal burns.

Thermal food burns are usually on the palate or posterior buccal mucosa, and appear as zones of

erythema and ulceration with necrotic epithelium peripherally. Electrical burns more commonly

affect the oral commissure (corner of the mouth). The lesions are usually initially painless,

charred and yellow with little bleeding. Swelling then develops and by the fourth day following the

burn the area becomes necrotic and the epithelium sloughs off.[5]

Electrical burns in the mouth are usually caused by chewing on live electrical wiring (an act that is

relatively common among young children). Saliva acts as a conducting medium and an electrical

arc flows between the electrical source and the tissues, causing extreme heat and possible tissue

destruction.[5][6]

Chemical injury[edit]

Caustic chemicals may cause ulceration of the oral mucosa if they are of strong enough

concentration and in contact for a sufficient length of time. The holding of medication in the mouth

instead of swallowing it occurs mostly in children, those under psychiatric care, or simply because

of a lack of understanding. Holding an aspirin tablet next to a painful tooth in an attempt to

relieve pulpitis (toothache) is common, and leads to epithelial necrosis. Chewable aspirin tablets

also need to be swallowed, and the residue quickly cleared from the mouth. Other caustic

medications include eugenol and chlorpromazine. Hydrogen peroxide, used to treat gum disease,

is also capable of causing epithelial necrosis at concentrations of 1–3%. Silver nitrate, sometimes

used for pain relief from aphthous ulceration, acts as a chemical cauterant and destroys nerve

endings, but the mucosal damage is increased. Phenol is used during dental treatment as a

cavity sterilizing agent and cauterizing material, and it is also present in some over the counter

agents again intended to treat aphthous ulcerations. Mucosal necrosis has been reported to

occur with concentrations of 0.5%. Other materials used in endodontics are also caustic, which is

part of the reason why use of a rubber dam is now recommended.[5]

Irradiation[edit]

As a result of radiotherapy to the mouth, radiation induced stomatitis may develop, which can be

associated with mucosal erosions and ulceration. If the salivary glands are irradiated, there may

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also be xerostomia (dry mouth), making the oral mucosa more vulnerable to frictional damage as

the lubricating function of saliva is lost, and mucosal atrophy(thinning) which makes a breach of

the epithelium more likely. Radiation to the bones of the jaws causes damage to osteocytes and

impairs the blood supply. The affected hard tissues become hypovascular (reduced number of

blood vessels), hypocellular (reduced number of cells) and hypoxic (low levels of

oxygen). Osteoradionecrosis is the term for when such an area of irradiated bone does not heal

from this damage. This usually occurs in the mandible, and causes chronic pain and surface

ulceration, sometimes resulting in non healing bone being exposed through a soft tissue defect.

Prevention of osteradionecrosis is part of the reason why all teeth of questionable prognosis are

removed before the start of a course of radiotherapy.[5]

Medical CareThe treatment of ulcerated lesions varies depending upon size, duration, and location.

With ulcerations induced by mechanical trauma or thermal burns from food, remove the obvious cause. These lesions typically resolve within 10-14 days.

Ulcerations associated with chemical injuries will resolve. The best treatment for chemical injuries is preventing exposure to the caustic materials.

With electrical burns, verify status and administer the vaccine if necessary. Patients with oral electrical burns are usually treated at burn centers.[14]

Antibiotics, usually penicillin, may be administered to prevent secondary infection, especially if the lesions are severe and deeply seated. Most traumatic ulcers resolve without the need for antibiotic treatment.

Treatment modalities for minor ulcerations include the following:o Removal of the irritants or causeo Use of a soft mouth guardo Use of sedative mouth rinseso Consumption of a soft, bland dieto Use of warm sodium chloride rinseso Application of topical corticosteroidso Application of topical anesthetics