Virus and bullous dermatoses

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Virus and bullous dermatoses
Lector Shkilna M.
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CONENT

• 1.Clinical types of pemphigus
• Pemphigus vulgaris
• Pemphigus foliaceus
• Pemphigus vegetans
• Pemphigus erythematous
• 2. Classification
• 3.Diagnosis of HSV Infections
• 4. Epidemiology
• 5. Disease caused by Herpes Simplex Viruses
• 6. Disease caused by Herpes Zoster
• 7. Other human Herpes Viruses Disease
• 8. Diagnosis and treatment

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Skin layers
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Bulla formed due to fluid in the skin and fluid
collection occurs at sites where the cohesion on
the skin is weak

• subcorneal
• intra epidermal, due to individual
  keratinocytes
• dermo epidermal junction

A circumscribed collection of free fluid more
than 0,5 sm in diameter
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Pemphigus ( from the Greek pemphix) -

• meaning blister is a rare, of autoimmune,
  intraepidermal blistering diseases involving the
  skin and mucous membranes.
• It is a particular group of bullous dermatoses
  presenting with a distinct histopathology
  characterized by intraepidermal bulla and
  acantholysis.

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Acantholysis

• Normally the cells of the spinous cell layer are
  kept together by the of desmosomes and a series
  extracellular proteins known as cadherins.
• Autoantibodies, (IgG) are directed against the
  extracellular protein desmoglein 3 which is one
  of the cadherins. Desmoglein 3 is treated as an
  antigen and this process produces the separation
  of the cells of the spinous cell layer with
  consequent formation of vesicles and bullae. The
  process of destruction (lysis) of the
  intercellular connections (desmosomes) of the
  epithelial cells is known as acantholysis.

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Acantholysis

• Acantholytic cells
• is (which are present both in the blister cavity
  and at the edge of the blister) are rounded
  keratinocytes. The cytoplasm
• is condensed in the periphery resulting in a
  perinuclear pale halo.

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Four clinical types of pemphigus

• 1. Pemphigus vulgaris cleft is deeply situated
  between the basal layer and the rest of epidermis
  and there is sufficient fluid to produce the
  characteristic bulla.
• 2. Pemphigus vegetans superficial cleft and
  proliferate changes producing papillomatous
  masses.
• 3. Pemphigus foliaceus subcorneal cleft and
  little fluid.
• 4. Pemphigus erythematous abortive phase of
  Pemphigus foliaceus.

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Pemphigus vulgaris

• It is an autoimmune disease caused by drugs,
  chemicals and infections.
• Pathology.
• 1. The bulla of Pemphigus vulgaris are
  intra-dermal and irregular in shape with acute
  lateral margins .
• 2. They are formed by the separation of
  acantholytic epidermal cells( Tzanck cells ).
• 3. Acantholytic cells may be in the bulla cavity.
• 4. Dermis beneath the bulla shows number of
  inflammatory cells including a few lymphocytes
  and plasma cells.

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Skin lesions predominantly present on
Axillae
Trunk
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Skin lesions

• Tense of flaccid bulla appear on normal skin.
• The lesions may be few and sparse, or extensive.
• The eruption is usually symmetrical.
• They are usually irregular in shape.
• On rupturing, form painful erosions which have a
  tendency to spread .
• Positive Nikolskys sign.

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Nikolsky's sign

• application of tangential pressure on normal
  skin results in formation of anew bulla or if
  applied to pre-existing bulla results in the
  spread of bulla (Nikolskys sign).
• where the epidermis is detached and slipping free
  from the dermis with slight pressure

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Mucosal lesions

• Eventually present in all patients oral mucosa
  moat frequently involved.
• The mouth is often involved, but denuded areas
  may be seen on conjunctive, vagina, nose.
• Patients have painful raw areas with detachable
  shreds of epithelium in the mouth, these may
  extend to the pharynx and larynx resulting in
  dysphagia and hoarseness.

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Pemphigus foliaceus

• Pathology
• It is superficial pemphigus (in granular cell
  layer or under the stratum corneum).

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Skin lesions

• Flaccid bulla and exfoliating scales.
• Usually flaccid bulla develop first on the face.
• Slowly the disease spreads symmetrically till the
  whole of the integument is covered with bulla
  (when it looks like erythroderma).
• Bulla rapture rapidly and produce a moist, red,
  raw, and oedematous surface and flake-like
  plaques of imperfectly keratinized, horny cells.
• The conjunctivae and mucosa may be affected.
• The scalp may also be involved it is covered
  with moist, yellowish scales. The hair may fall.

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Pemphigus vegetans

• It is the rarest variety of pemphigus.
• Individuals of any
• group may be
• affected.
• It is more common in females than in males.

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Skin lesions

• The initial lesions, in the form of broken
  bullae, appear on the mucosa of the lips, angle
  of mouth or nose.
• Later, they develop in the axillae, groins and
  some-times on the other parts of the body.
• When ruptured, the bulla develop into moist,
  superficial ulcers.
• The ulcers undergo proliferative changes
  producing fungoid vegetations with malodorous
  discharge.
• The vegetations may also seem to arise de novo on
  the normal skin.
• Nikolskys sign is often positive.

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Pemphigus erythematous

• Skin lesions
• The early lesions which are erythematous and
  crusted, appear on the nose and ears, resembling
  lupus erythematosus both in their location and
  appearance.
• However, the lesions exhibit a moist, raw surface
  when the crust is removed.
• The greasy crust may indicate seborrhoeic
  dermatitis.
• These lesions may appear along with bullae on the
  chest and extremities.
• The eruption is symmetrical in distribution.

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Diagnosis

• Laboratory diagnosis of pemphigus is based on
• Tzanck Smear.
• Histology.
• Immunopathology.

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Preparation of Tzanck smear

• The vesicle should be unroofed or the crust
  removed, and the base scraped with a scalpel or
  the edge of a spatula.
• The material is transferred to a glass slide by
  touching the spatula to the glass slide
  repeatedly but gently.
• The slide should be clean, since cells will not
  adhere to a slide marred by fingerprints.
• In the case of blistering disorders
• The intact roof of a blister is opened along one
  side, folded back and the floor gently scraped.
• The material thus obtained is smeared onto a
  microscopic slide, allowed to air dry, and
  stained with Giemsa or any of the Romanowskys
  stains.

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Tzanck Smear findings in bullous disorders

• Pemphigus (Acantholytic cells)
• Bullous pemphigoid (Predominantly eosinophils)
• Chronic bullous disease of childhood
  (Predominantly polymorphs)
• Varicella zoster infection (Multinucleated giant
  cells)
• Herpes simplex infection (Multinucleated giant
  cells)
• Toxic epidrmal necrolysis (Necrotic cells).

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ImmunopathologyTwo classes of tests
areavailable

• 1. Direct immunofluorescence (DIF) Done on the
  skin of the patient, shows intercellular deposits
  of Ig G and C3 giving a fish net appearance.
• 2. Indirect immunofluorescence (IIF) Done on
  patient serum to detect autoantibody titers
  correlate with the clinical activity and may be a
  useful guide to the dose of oral steroids needed.

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Treatment

• Supportive treatment
• Local hygiene of mucosal and skin lesions.
• Therapeuticas well as prophylactic use of
  antibiotics (forcoetaneous infection) and
  anticandidal agents (formucosal lesions).
• Maintenance of water and electrolyte balance.

• Specific treatment
• Specific treatment depends on the judicious use
  of corticosteroids and immunosuppressive drugs
  since pemphigus
• is an autoimmune disorder.

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Treatment

• Corticosteroids
• Two regimes are commonly used
• Daily dose of 1 -2 mg / kg body weight of
  prednisoloneequivalent is used to suppress
  disease activity andsteroids are tapered when
  the disease is controlledthis form of steroid
  therapy is associated withsubstantial adverse
  events.
• Monthly steroid therapy.
• Monthly 1-2 mg / kg of betamethasone orally
  /dexamethasone intravenous is given.
• Usually combined with immunosuppressivetherapy.
• gt May induce remissions with less side effects.

• Immunosuppressive therapy
• Drug regimes
• Azathioprine Usually along with oral
  steroidtherapy. 2-3 mg/kg of body weight till
  clearing ofdisease maintain on 1 mg / kg.
• Methotrexate Usually along with oral
  steroidtherapy given as weekly 20-25 mg.
• Cyclophosphamide Usually along with oral
  steroidtherapy. As daily dose (50-200 mg) or
  monthlybolus dose (500-1000 mg) intravenously.

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Human Herpes Viruses

• Latent Viruses

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Vesicle

• Description
• Circumscribed collection of free fluid
• Up to 0.5 cm in diameter

Herpes zoster
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EROSION

• Description
• A focal loss of epidermis
• erosions do not penetrate
• below the dermoepidermal
• junction
• and therefore heal without scarring

Toxic epidermal necrolysis
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CRUST

• Description
• Is a collection of dried serum and cellular
  debris- a scab
• Examples
• Acute eczematious inflammation
• Atopic on the face
• Impetigo- golden or honey colored
• Tinea capitis

Impetigo. A thick, honey-yellow adherent crust
covers the entire eroded surface.
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Classification

• There are 25 families in the Herpeotoviridae but
  only 6 of them infect man with any regularity.
• Herpes Simplex virus Type 1 (HSV-1)
• Herpes Simplex virus Type 2 (HSV-2)
• Epstein Barr virus (EBV)
• Cytomegalovirus (CMV)
• Varicella Zoster virus (VZV)
• Human Herpes virus 6
• Human Herpes virus 8

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Herpes Simplex Virus (HSV)

• These are very large viruses and their genome
  encodes at least 80 proteins.
• Half are not directly involved in the virus
  structure.
• Almost any human cell type can be affected by
  HSV.

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Epidemiology

• HSV-1 and 2 infections are life-long.
• The virus is found in the lesions on the skin but
  can be present in body fluids including saliva
  and vaginal secretions.
• As a result of poor hygiene in underdeveloped
  countries, HSV-1 antibodies are found in more
  than 90 of children.

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Epidemiology 2

• HSV-2 is normally spread sexually and is found in
  the anus, rectum and upper alimentary tract as
  well as the genital area.
• An infant can be infected at birth by a
  genitally-infected mother.
• The infant can also be infected in utero if the
  mothers infection spreads.
• Because of the infants underdeveloped immune
  system, the resulting infection can be very
  severe and sometimes be deadly.

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Disease caused by Herpes Simplex Viruses

• Oral Herpes - Cold sores
• Herpetic gingiovostomatitis, the infection, often
  initially on the lips spreads to all parts of the
  mouth and pharynx.

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Disease caused by Herpes Simplex Viruses

• Eczema Herpeticum
• This is found in children with active eczema.
• The virus can spread to other organs such as the
  liver and adrenals.

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Disease caused by Herpes Simplex Viruses

• Genital Herpes
• Is usually the result of HSV-2.
• Primary infection is often asymptomatic but many
  painful lesions can be developed on the shaft of
  the penis and vulva, vagina, cervix and perianal
  region of women.

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Genital Herpes
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Genital Herpes

• In both sexes, the urethra can be involved.
• Genital Herpes infections can be accompanied by a
  variety of symptoms including fever, myalgia,
  glandular inflammation of the groin area
  (inguinal).
• Some patients have only infrequent recurrences
  but others experience recurrences as often as
  every 14-21 days.

• Is usually the result of HSV-2.
• Primary infection is often asymptomatic but many
  painful lesions can be developed on the shaft of
  the penis and vulva, vagina, cervix and perianal
  region of women.

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Diagnosis of HSV Infections

• Cells may be obtained from the base of the lesion
  (called a Tzank smear) and histochemistry
  performed.
• These can be seen in the smears as multinucleated
  giant cells and contain Cowdry type A inclusion
  bodies.

• The cells can also be stained with specific
  antibodies in an immunofluorescence test.
• It can also be detected by viral DNA by in situ
  hybridization.
• Type-specific antibodies can distinguish between
  HSV-1 and HSV-2.

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Diagnosis of HSV Infections
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HERPES ZOSTER

• Reactivation of HVZ
• dermatomal distribution
• may recur
• can disseminate in immunocompromised patients
• complications
• post herpetic pain
• ophthalmic zoster -corneal scarring and loss of
  vision

DIAGNOSIS
CLINICAL EM of vesicle fluid SEROLOGY IgM
detection
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Pain and hyperaesthesia
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Pain and hyperaesthesia
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Pain and hyperaesthesia
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OTHER HUMAN HERPES VIRUSES

• HHV6
• virus replicates in T and B cells
• infection occurs in first 3 years of life
• Clinical Exanthem subitum (roseola infantosum)
• mild acute febrile illness
• incubation period of 2 weeks
• fever lasts several days
• macular papular rash appears within 2 days of
  fever
• 85 of adults carry virus in saliva

• HHV7
• isolated from CD4 positive cells
• virus present in saliva of gt75 of adults
• role in disease unclear
• Evidence of infection present (seroconversion)
• HHV8
• detected in epithelial cells of Kaposi sarcoma
• also present in semen
• postulated as cause of Kaposi sarcoma

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Exanthem subitum (roseola infantosum)
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Treatment

• Acyclovir
• A Safe and extremely well-tolerated drug.
• More than 35 million patients have been
  consistent and reassuring.
• Some authorities have proposed making acyclovir
  available as a non-prescription drug.
• Adverse effects, usually mild, include nausea,
  vomiting, rash and headache.

• Valacyclovir
• New antiviral agent
• Is the 1-valine ester prodrug of acyclovir.
• It has an oral bioavailability three to five
  times greater than that of acyclovir.
• Several large trials have shown that it is safe
  and well tolerated.

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