VIRAL INFECTIONS

IHAB YOUNIS, MD

Part I

Some properties of viruses

• Possess no membranes, cytoplasm, ribosomes, or other cellular components

• They cannot move or grow

• They can only reproduce inside a host cell

• They consist of 2 major

parts : a protein coat

(capsid) and hereditary

material (DNA or RNA)

1-virus attaches to a cell

2-Virus penetrates cell membrane&injects nucleic acid into it

3-Virus nucleic acid replicates inside the cell

4-New viral nucleic acids are packaged into viral particles&released

Viral life cycle

Related to Viruses

• Viroids : even smaller than viruses, consist of RNA strands that lack a protein coat

• Prions : infectious agents that are believed to be the cause of Mad Cow Disease, relatively newly found and much is not known about them

Viruses cause:

I-Proliferation of epidermal cells

II-Destruction leading to vesicle formation

III-Inflammatory response

Warts

(Verrucae)

Etiology• The DNA-containing human papillomavirus

(HPV)• Some believe that the number of its genotypes

has approached 130 or more • The virus enters the skin after direct contact with

recently shed viruses kept alive in warm, moist environments such as a locker room, or by direct contact with an infected person. The entry site is often an area of recent injury

• The incubation period: 1-8 months

• Contrary to popular mythology, touching a frog will not cause warts

Types

1 -Common warts (verrucae vulgaris)

• Develop anywhere but common on the hands, feet and knees

• Gray to flesh colored, raised from the skin surface & have rough, hornlike projections

2 -Plantar warts

• The only painful type

• Occur on the plantar surface, usually in high-pressure areas such as the heel and the metatarsal heads

• Usually flat because of pressure

Firm, hyperkeratotic lesions with tiny pinpoint petechiae centrally or smooth surface with a gray-yellow color

Mosaic wartsMultiple plantar warts

3-Plane warts (verrucae plana)

• Most commonly seen on the face & back of hands

• Small individual papules about 5 mm in diameter

4-Digitate warts • Common on the head and neck

5 -Anogenital warts (cond.accuminata)

• Until 1907, they were believed to be a form of syphilis or gonorrhea

• Roughly, 10% of the general population in the USA have been infected by genital HPV at some time in their life

• 2 types:

Pink-to-brown

papillomatous papules

or nodules on the

genitalia, perineum,

crural folds and anus

Vary in size and can form large, exophytic, cauliflowerlike masses

Discrete flat papules, 1-3 mm in size can present on the shaft of the penis &pubic skin. Also, cauliflower masses can exist

• 50% of homosexual men with SCC of the anus have a history of anorectal warts

• On the cervix they are subclinical lesions

• Colposcopic examination with 3% acetic acid solution is required for identification

• Pap smear is required annually for fear of SCC

• Pap smear should be performed annually on all women once they become sexually active or when they have reached the age of 18 years if they have remained abstinent

• Once a woman has had findings within the reference range on 3 or more consecutive annual Pap smears, the Pap smear may be performed less frequently

HistopathologyHyperplasia of all epidermis

Papillae bent towards the center

Koilocytes(altered keratinocytes) with deeply basophilic nuclei & halo

Koilocytes(altered keratinocytes) with deeply basophilic nuclei & halo

TreatmentDestruction by:

1-Chemical agents:

A- keratolytic agents

B-Cytotoxic agents

C- Immune response modifiers

D-Others

2-Physical agents

A-Keratolytic agentsTCA 25-90% sol.Salicylic acid 12-26%

Alone or with lacticVery powerful but painful Mild

Applied directly on a weekly basis. As the acid dries, a white frosting develops and should be

powdered with sodium bicarbonate to remove any

unreacted acid

Applied daily for 3 M alone or in combination with lactic acid

and collodion or in an adhesive plaster

Can be used on all types of warts

Used primarily to treat nongenital warts

B-Cytotoxic agentsPodophyllin 10-25% in

tincture benzoin5-Flurouracil 5% cream

Arrests mitosis in metaphase

Interferes with synthesis of DNA and RNA

Appllied by physician weekly for 6 weeks

Appllied by patient 1-3 times/w for as needed

Clean the skin, apply avoiding normal skin &

allow to dry for½ h. then remove. Subsequent applic.

can be for 1-4 h.

Same but remove after 3-10 h.

Effective only in anogenital warts

?Effective in all types

Contraindicated in pregnancy&on bleeding areas

Not formally indicated

C- Immune response modifiersImiquimod (Aldara cr.) Interferon alfa

Produces interferon

alfa,TNF&IL-1,6, and 8

Potent immuon-

modulator& antiviral

Patient-appliedPhysician appllied

Applied 3 times per week, removed after 6-10 h. for up to 16 w.

250,000 IU per wart iniected IL.Results

appear in1-2M or repeat

Local reactions commonMay affect liver&blood cells

D-Other treatments

1-Retinoids

• Retinoic acid (Retin–A) topically may be usefull for plane warts

• Etretinate orally may be of some help in immunocopromised patiets

2- Formalin 2-3% solution

• May be effective for plantar warts

• Affected area is soaked for 15-20 min./day

• It is virucidal

• Time consuming&dries skin

3-Intralesional bleomycin

• 1mg/ml conc. is injected intralesionally till blanching

• A hemorrhagic eschar develops in 2-3 W.

• It is painful so, spared for refractory cases

4- Cimetidine (Tagamet)

• Orally:40mg/kg/day for3 months

• Has weak immunomodulatory effects

• Conficting results

5-Hypnosis

• Uncontroled studies

Physical methods

1-Electrosurgery • Electrosurgical equipment converts domestic alter- nating current into high frequency alternating current• When this current meets the high resistance of the skin, it produces heat

• Under local anaesthesia, the growth is curetted away and the base

burned by electrodessication

(needle in contact)or

fulgration(spark)

• The treated area appears raw immediately after surgery and develops a scab. Five to ten days later fresh skin appears which gradually blends in to the normal skin color

• 20% of warts can be expected to recur within a few months

2-Diathermy:• A-Unipolar:Current is delivered through a

unipolar needle (+ve electrode) to the point required then passes in patien’s body to a –ve electrode connected to the patient

• a burn at the –ve electrode may occur due to faulty connection

• B-Bipolar:Current is produced and collected by the 2 poles avoiding the hazards of unipolar diathermy

Advices to the patient

• Your wound may be tender 1-2 hours after the curettage when the local anaesthetic wears off

• Leave the dressing in place for 24 hours • Avoid strenuous exertion&stretching of the area• Keep the wound dry for 48 hoursIf the wound

becomes red or very painful, consult your doctor• The wound will take approximately 2-3 weeks to

heal over. The scar will initially be red and raised but usually reduces in color and size over several months

3-Cryotherapy • Liquid nitrogenis the most commonly used agent ( boiling pont -196°C)

• Many practitioners use a spray, but cotton wool-tipped sticks are still widely used and can be preferable when treating children or for warts near the eyes

• It is common practice to freeze until a halo of frozen tissue appears around the wart and then another time for 5 to 30 seconds, depending on site and size of wart

• Patients should be

warned that cryo-

therapy is painful

and blistering may occur. Caution must be used when freezing warts over tendons and in patients with poor circulation

4-Lasers• Carbon Dioxide Laser Periungual and subungual lesions, which can be difficult to eradicate by other methods, may be particularly appropriate for this treatment• Pulsed Dye Laser -Depends upon the energy absorption within the

capillary loops of the wart and hence localized tissue necrosis- Pain and scarring are less than with the CO2laser

5-Photodynamic Therapy

• Depends upon the uptake by abnormal cells of a chemical, usually amino-laevulinic acid (Levulan), topically

• After 3-6 h photo-oxidation is invoked by irradiation of affected tissue using laser or non-laser light for 5-45 min.

Epidermodysplasia verruciformis

Etiology• Results from a genetically determined defect in

cutaneous immunity that makes them susceptible to widespread viral infection

• Patients are usually infected with more than 30 types of HPV. 90% of EV-associated skin cancers contain HPV types 5,8, and 47

• Carcinogenic cofactors, such as ultraviolet B and x-ray irradiation, are likely involved in the progression from benign warts to malignancy

Clinically• The disease usually begins in infancy or

early childhood

• Skin lesions on the face are indistinguishable from plane warts

Hypopigmented macules and reddish brown plaques with slightly scaly surfaces occur on the trunk & limbs with a protracted course

• Malignant transformation of skin lesions has been observed in more than one half of the patients followed up for 20-30 years• Most cancers remain local, and metastasis is extremely uncommon

BOWENOID PAPULOSIS

• Described in 1977 by Kopf and Bart

• Induced virally by HPV

• Lesions appear to run a benign course, although a number of case reports associate BP with malignant invasive transformation (2.6%)

May be considered a transitional state between a genital wart and Bowen disease

Clinically

• Occurs in young sexually active persons• Spontaneous regression occurs within several

months• A more protracted course is believed to occur in

older patients and, possibly, with lesions consistent with certain HPV types. These lesions may last as long as 5 years, or they may never regress completely

• The lesions tend to be asymptomatic but can be inflamed, pruritic, or painful

• Presents as solitary or multiple, small, pigmented (red, brown, or flesh-colored) papules with a flat-to-verrucous surface

• The lesions can coalesce into larger plaques

• Lesions occur most commonly on the shaft of the penis or the external genitalia of females

Bowen

Bowenoid

• Circumscribed epidermal proliferation composed of pleomorphic cells with clumped nuclei and numerous

occasionally abnormal mitoses• The integrity of the dermal- epidermal border is preserved• The pattern may be identical to Bowen disease

or squamous cell carcinoma in situ, occurring on nongenital skin

Treatment

• Podophyllin 10-25% in tincture benzoin weekly

• TCA 25% every 2 weeks

• Imiquimod (Aldara) 3 nights per wk

MOLLUSCUMCONTAGIOSUM

Etymology: Latin molluscus, thin-shelled, soft.Marine invertebrates of the phylum Mollusca, typically having a soft unsegmented body.

Etiology

• MCV is a DNA ds virus (largest known virus)

• Type1 responsible for 76-97 %

• Type 2

Epidermal lobules compressing papilla

Histopathology

Molluscum bodies

(cytoplasmic inclusions of viruses)

Clinically• Incubation period: 2 weeks-6 months

• Distribution– In children: lesions mainly on the trunk and

extremities– In adults: lesions often are located on the

lower abdominal wall, inner thighs, pubic area, and genitalia

• Shiny, pearly white,

hemispherical,

umbilicated papule

• Self-limited but can

persist for several

years

Diagnosis

• Freezing accentuates umbilication

• Microscopic examination of crusshed lesion

Differential diagnosis

PyogenicGranul.

Kerato-acanth.

Epithelioma

Treatment• ? Wait for spontaneous resolution

• Destruction:

I-By physical methods:

Cryotherapy

Electrocautary

Laser

Expression by forceps

II-By topical cauterizing agents:

1-TCA

2-Silver nitrate

3-Phenol

4-Wart preparations

5-Others

1-Trichloroacetic acid• Causes less irritation&can be used in anal areas • Response:incomplete&frequent recurrences

occur• Repeat q1-2wk • Safety for use during pregnancy has not been

established• Contraindications: premalignant or malignant

lesions

2-Silver nitrate

• Applied daily for approximately 5 d

• Safety for use during pregnancy has not been established

3-Phenol

• 10-20%

• Painful

4-Wart preparations

• Salicylic acid 20%

Lactic acid 5% }Collomack

Polidocanol(topical anesth.) 2%

• Once or twice weekly

Other topical therapies:

• Tretinoin

• Podophyllin

III-Systemic drugs:

• Cimetidine (Tagamet) orally:40mg/kg/day for 2 months