1. Virus and bullous dermatoses
Lector: Shkilna M.

2. 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

3. Skin layers

4. A circumscribed collection
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

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Skin lesions predominantly present on:
Axillae
Trunk

11. 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 Nikolsky’s sign.

12. 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 (Nikolsky’s sign).
where the epidermis is detached and slipping free from the dermis with slight pressure

13. 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.

14. Pemphigus foliaceus Pathology:
It is superficial pemphigus (in granular cell layer or under the stratum corneum).

15. 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.

16. 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.

17. 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.
Nikolsky’s sign is often positive.

18. 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.

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

20. 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 Romanowsky’s stains.

21. 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).

22. Immunopathology Two classes of tests are available:
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.

23. Treatment
Supportive treatment
Local hygiene of mucosal and skin lesions.
Therapeutic as well as prophylactic use of antibiotics (for coetaneous infection) and anticandidal agents (for mucosal 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.

24. Immunosuppressive therapy:
Treatment
Corticosteroids
Two regimes are commonly used:
Daily dose of 1 -2 mg / kg body weight of prednisolone equivalent is used to suppress disease activity and steroids are tapered when the disease is controlled; this form of steroid therapy is associated with substantial adverse events.
Monthly steroid therapy.
Monthly 1-2 mg / kg of betamethasone orally / dexamethasone intravenous is given.
Usually combined with immunosuppressive therapy.
> May induce remissions with less side effects.
Immunosuppressive therapy:
Drug regimes:
Azathioprine: Usually along with oral steroid therapy. 2-3 mg/kg of body weight till clearing of disease: maintain on 1 mg / kg.
Methotrexate: Usually along with oral steroid therapy; given as weekly mg.
Cyclophosphamide: Usually along with oral steroid therapy. As daily dose ( mg) or monthly bolus dose ( mg) intravenously.

25. Human Herpes Viruses
Latent Viruses

26. Vesicle Description Herpes zoster
Circumscribed collection of free fluid
Up to 0.5 cm in diameter
Herpes zoster

27. EROSION Description A focal loss of epidermis;
erosions do not penetrate
below the dermoepidermal
junction;
and therefore heal without scarring
Toxic epidermal necrolysis

28. CRUST Description Examples
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.

29. 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

30. 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.

31. 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.

32. 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 mother’s infection spreads.
Because of the infant’s underdeveloped immune system, the resulting infection can be very severe and sometimes be deadly.

33. 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.

34. 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.

35. 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.

36. Genital Herpes

37. 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 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.

39. 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.

40. Diagnosis of HSV Infections

41. 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

42. Pain and hyperaesthesia

43. Pain and hyperaesthesia

44. Pain and hyperaesthesia

45. 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 >75% 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

46. Exanthem subitum
(roseola infantosum)

47. Treatment Acyclovir Valacyclovir
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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