Viral infections

المرحلة الخامسة / مجموعة A

د.مازن حامد
DERMATOLOGY

Viral infections

Viral warts
Most people will have a wart at some time in their lives. Their prevalence is highest in childhood, and they affect an estimated 4–5% of schoolchildren in the UK.

Cause

Warts are caused by the human papilloma virus (HPV),which has still not been cultured in vitro. Nevertheless,more than 100 ‘types’ of the virus have been recognized by DNA sequencing; each has its own range of clinical manifestations. HPV-1, 2 and 4, for example, are found in common warts, whereas HPV-3 is found in plane warts, and HPV-6, 11, 16 and 18 are most common in genital warts. Infections occur when wart virus in skin scales comes into contact with breaches in the skin or mucous membranes.

Presentation

Warts adopt a variety of patterns , :
Common warts . The first sign is a smooth skin-coloured papule, more easily felt
than seen. As the lesion enlarges, its irregular hyperkeratotic surface gives it the classic ‘warty’ appearance. usually on the hands but are also face and genitals. They are often multiple than single. Pain is rare.
Plantar warts. These have a rough surface, protrudes only slightly from the skin and is surrounded by a horny collar. On paring, the presence of bleeding capillary loops allows plantar warts to be distinguished from corns. Often multiple, plantar warts can be painful. Mosaic warts. These rough marginated plaques made up of many small tightly packed
but discrete individual warts. most common on the soles , also seen on palms and around fingernails. Painless.
Plane warts . These smooth flat-topped papules are most common on the face and brow, and on the backs of the hands. Usually skin-coloured or light brown, they become inflamed as a result of an immunological reaction, just before they resolve
spontaneously. Lesions are multiple, painless and,like common warts, are sometimes arranged along a scratch line.
Facial warts. These are most common in the beard area of adult males and are spread by shaving. Adigitate appearance is common. Lesions are often ugly but are painless.
Anogenital warts (condyloma acuminata).
Papillomatous cauliflower-like lesions, with a moist macerated vascular surface, can appear anywhere in this area. They may coalesce to form huge lesions causing discomfort and irritation. The vaginal and anorectal mucosae may be affected. The presence of anogenital warts in children raises the spectre of sexual abuse, but is usually caused by autoinoculation from common warts elsewhere.


Course
Warts resolve spontaneously in the healthy as the immune response overcomes the infection. This happens within 6 months in some 30% of patients, and
within 2 years in 65%. Such spontaneous resolution, sometimes heralded by a punctate blackening caused by capillary thrombosis , leaves no trace.
Mosaic warts are notoriously slow to resolve and often resist all treatments. Warts persist and spread in immunocompromised patients (e.g. those on immunosuppressive
therapy or with lymphoreticular disease).Seventy per cent of renal allograft recipients will have warts 5 years after transplantation.

Complications

1 Some plantar warts are very painful.
2 Epidermodysplasia verruciformis is a rare inherited disorder in which there is a universal wart infection, with HPV of unusual types.
3 Malignant change is rare, although infections with HPV of certain genital strains predispose to cervical and penile carcinoma. HPV infections in immunocompromised patients (e.g. renal allograft recipients) linked with skin cancer,

Differential diagnosis

• Molluscum contagiosum • Plantar corns are found on pressure areas;
• Granuloma annulare • Condyloma lata are seen in syphilis. confused with condyloma acuminata. The lesions are flatter, greyer and less well defined. If in doubt, look for other signs of secondary syphilis and carry out serological tests.
• Amelanotic melanomas and other epithelial malignancies

Treatment

Many warts give no trouble, need no treatment and will go away by themselves. Otherwise treatment will depend on the type of wart. Destruction by cryotherapy is less likely to cause scars than excision or electrosurgery.
Palmoplantar warts
Home treatment is best, with one of the many wart paints now available .Most
contain salicylic acid (12–20%). Paints should be applied once daily, after
moistening the warts in hot water for at least 5 min.After drying, dead tissue and old paint are removed with an emery board or pumice stone. Warts on the plantar surface should be covered with plasters although this is not necessary elsewhere. Side-effects are rare if these instructions are followed. Wart paints should not be applied to facial or anogenital skin, or to patients with adjacent eczema.If no progress made after the regular and correct use of a salicylic acid wart paint for 12 weeks,
then a paint containing formaldehyde or glutaraldehyde. A useful way of dealing with multiple small plantar warts is for the area to be soaked for 10 min each night in a 4% formalin solution, although a few patients become allergic to this. Cryotherapy with liquid nitrogen (at –196°C) is more effective than the less cold, dry ice or dimethyl
ether/propane techniques. it is painful. Acotton-tipped applicator dipped into liquid nitrogen is applied to the wart until a small frozen halo appears in the surrounding normal skin. The HPV, and also other viruses such as HIV,can survive in stored liquid nitrogen and so, once used, a bud should not be dipped back into the flask. Treatment with a liquid nitrogen spray gun does not carry the risk of cross-infecting patients, and is quicker and as effective. The use of two freeze–thaw cycles increases the clearance rate of plantar warts but not of hand warts. If further treatments are necessary, the optimal interval is 3 weeks. The cure rate is higher if plantar warts are pared before they are frozen. If there has been no improvement after four or five treatments there is little to be gained from further freezings. Blisters should not be provoked intentionally.
Anogenital warts Women with anogenital warts, or who are the partners of men with anogenital warts, should have their cervical cytology checked regularly as the wart virus can cause cervical cancer.The focus has shifted towards self-treatment using podophyllotoxin (0.5% solution or 0.15% cream) or imiquimod (5% cream). Both are irritants and should be used carefully.Imiquimod is an immune response modifier that induces keratinocytes to produce cytokines, leading to wart regression, and may help to build cell-mediated immunity for longlasting protection. It is applied as a thin layer three times weekly and washed off with a mild soap 6–10 h after application. Podophyllin paint (15%) is used much less often now. It should be
applied carefully to the warts and allowed to dry before powdering with talcum. On the first occasion it should be washed off with soap and water after 2 h but, if there has been little discomfort, this can be increased stepwise to 6 h. Treatment is best carried out weekly by a doctor or nurse, but not by the patient. Podophyllin must not be used in pregnancy. Cryotherapy, electrosurgery and laser treatment are effective .
Facial common warts best treated with electrocautery or ahyfrecator, but also cryotherapy. Scarring is an unwanted complication. Shaving, ifessential, should be with a brushless foam and a disposable razor.
Plane warts On the face these are best left untreated and the patient reassured that spontaneous resolution will occur. When treatment is demanded,the use of a wart paint or imiquimod cream is reasonable. Gentle cryotherapy .
Solitary, stubborn or painful warts removed under local anaesthetic with a curette. Surgical excision is never justifiable Bleomycin can injected into such warts.


Varicella (chickenpox)

Cause

The herpes virus varicella-zoster is spread by the respiratory route; its incubation period is about 14 days.

Presentation and course

Slight malaise is followed by the development of papules, which turn rapidly into clear vesicles, the contents of which soon become pustular. Over the next few days the lesions crust and then clear, sometimes leaving white depressed scars. Lesions appear in crops, are often itchy, and are most profuse on the trunk and least profuse on the periphery of the limbs (centripetal). Second attacks are rare. Varicella can be fatal in those who are immuncompromised.

Complications

• Pneumonitis, .• Secondary infection of skin lesions.• Haemorrhagic or lethal chickenpox in the immunocompromised. • Scarring.

Differential diagnosis

Smallpox, has been universally eradicated.

Investigations

None are usually needed.

Treatment

Aciclovir, famciclovir and valaciclovir reserved for severe attacks and for immunocompromised patients; for the latter, prophylactic aciclovir can also be used to prevent disease if given within a day or two of exposure. In mild attacks, calamine lotion topically is all that is required.A live attenuated vaccine is now available. It is not universally effective and should not be given to patients with immunodeficiencies or blood dyscrasias who might not be able to resist even the attenuated organism.

Herpes zoster

Cause
Shingles too is caused by the herpes virus varicellazoster.An attack is a result of the reactivation, usually for no obvious reason, of virus that has remained dormant in a sensory root ganglion since an earlier episode of chickenpox (varicella). The incidence of shingles is highest in old age, and in conditions such as Hodgkin’s disease, AIDS and leukaemia, which weaken normal defence mechanisms. Shingles does not occur in epidemics; its clinical manifestations are caused by virus acquired in the past. However, patients with zoster can transmit the virus to others in whom it will
cause chickenpox.


Presentation and course
Attacks usually start with a burning pain, soon followed by erythema and grouped, sometimes bloodfilled,vesicles scattered over a dermatome. The clear vesicles quickly become purulent, and over the space of a few days burst and crust. Scabs usually separatein 2–3 weeks, sometimes leaving depressed depigmented scars.
Zoster is characteristically unilateral.It may affect more than one adjacent dermatome.
The thoracic segments and the ophthalmic division of the trigeminal nerve are involved disproportionately often.

Complications

• Secondary bacterial infection is common.• Motor nerve involvement is uncommon,
• Zoster of the ophthalmic division of the trigeminal nerve can lead to corneal ulcers and scarring.A good clinical clue here is involvement of the nasociliary
branch (vesicles grouped on the side of the nose).• Persistent neuralgic pain, after the acute episode , is most common in the elderly.

Differential diagnosis

Occasionally, before the rash has appeared, the initial pain is taken for an emergency such as acute appendicitis or myocardial infarction. Otherwise,the dermatomal distribution, and the pain, allow zoster to be distinguished easily from herpes simplex,
eczema and impetigo.

Investigations

Cultures are of little help as they take 5–7 days,and are only positive in 70% of cases. Biopsy or Tzanck smears show multinucleated giant cells and a ballooning degeneration of keratinocytes, indicative of a herpes infection. Any clinical suspicions about underlying conditions, such as Hodgkin’s disease,chronic lymphatic leukaemia or AIDS, require further investigation.

Treatment

Systemic treatment should be given to all patients if diagnosed in the early stages of the disease. It is essential that this treatment should start within the first 5 days of an attack. Famciclovir and valaciclovir are as effective as aciclovir they depend on virus-specific thymidine kinase for their antiviral activity. All three drugs are safe, and using them may cut down the chance of getting postherpetic neuralgia, particularly in the elderly. If diagnosed late in the course of the disease,systemic treatment is not likely to be effective and supportive treatment with rest, analgesics
and bland applications such as calamine. Secondary bacterial infection should be treated appropriately.A trial of systemic carbamazepine, gabapentin or amitriptyline, or 4 weeks of topical capsaicin cream despite the burning sensation it
sometimes causes, for established post-herpetic neuralgia.


Herpes simplex

Cause

Herpesvirus hominis is the cause of herpes simplex.The virus is ubiquitous and carriers continue to shed virus particles in their saliva or tears. It has been
separated into two types. The lesions caused by type II virus occur mainly on the genitals, while those of type I are usually extragenital; however, this distinction is
not absolute.The route of infection is through mucous membranes or abraded skin. After the episode associated with the primary infection, the virus may become
latent, possibly within nerve ganglia, but still capable of giving rise to recurrent bouts of vesication(recrudescences).

Presentation

Primary infection
The most common recognizable manifestation of a
primary type I infection in children is an acute gingivostomatitis
accompanied by malaise, headache,fever and enlarged cervical nodes. Vesicles, soon turning into ulcers, can be seen scattered over the lips and mucous membranes. The illness lasts about 2 weeks.Primary type II virus infections, usually transmitted
sexually, cause multiple and painful genital or perianal blisters which rapidly ulcerate.
The virus can also be inoculated directly into the skin (e.g. during wrestling). A herpetic whitlow is one example of this direct inoculation. The uncomfortable
pus-filled blisters on a fingertip are seen most often in medical personnel attending patients with unsuspected herpes simplex infections.
Recurrent (recrudescent) infections.These strike in roughly the same place each time. They may be precipitated by respiratory tract infections (cold sores), ultraviolet radiation, menstruation or stress. Common sites include the face and lips (type I), and the genitals (type II), but lesions can occur anywhere. Tingling, burning or even pain is followed within a few hours by the development of erythema and clusters of tense vesicles. Crusting occurs within 24–48 h and the whole episode lasts 12 days.
Complications
• Herpes encephalitis or meningitis can occur.• Disseminated herpes simplex: in newborns, debilitated children or immunosuppressed adults.• Eczema herpeticum: patients with atopic eczema are susceptible to widespread cutaneous herpes simplex infections. Those looking after patients with atopic eczema should stay away if they have cold sores.• recurrent dendritic ulcers leading to corneal scarring.• EM.

Investigations

None are needed.if Doubts over the diagnosis, culturing the virus from vesicle fluid. Antibody titres rise with primary, but not with recurrent infections.
Treatment ‘Old-fashioned’ remedies suffice for occasional mild recurrent attacks; sun block may cut down their frequency. Dabbing with surgical spirit is helpful,and secondary bacterial infection can be reduced by topical bacitracin, mupirocin, framycetin or fusidic acid. For more severe and frequent attacks, acyclovir cream, if used at the first sign of the recrudescence, and applied five or six times a day for the first 4 days of the episode, cuts down the length of attacks and perhaps increases the intervals between them.Aciclovir tablets , 200 mg 5 times daily for 5 days, is more effective and can be given to those with widespread or systemic involvement.
Recurrences in the immunocompromised can usually be prevented by long-term treatment at a lower dosage. Famciclovir and valaciclovir are metabolized by the body into aciclovir and are as effective as aciclovir, having the additional advantage of needing fewer doses per day.


Molluscum contagiosum

This common pox virus infection can be spread by direct contact; e.g. sexually or by sharing a towel at the swimming bath.:Presentation and course:The I.P ranges from 2 to 6 weeks.Often several members of one family are affected. lesions are shiny, white or pink, and hemispherical; grow slowly up to 0.5 cm in diameter.A central punctum, which may contain a cheesy core,gives the lesions their characteristic umbilicated look.On close inspection a mosaic appearance may be seen. Multiple lesions are common and their distribution depends on the mode of infection.Atopic individuals and the immunocompromised are prone to especially extensive infections, spread by scratching and the use of topical steroids. Untreated lesions usually clear in 6–9 months, after a brief local inflammation. Large solitary lesions take longer. Some leave depressed scars.Complications:Eczematous patches around mollusca. secondarily infection.

Differential diagnosis:

Boil. .Keratocanthoma..intradermal naevus .cystic basal cell carcinoma . warts

Investigations

None are usually needed, but the diagnosis can be confirmed by looking under the microscope for large swollen epidermal cells, easily seen in unstained preparations
of debris expressed from a lesion.

Treatment

Many simple destructive measures cause inflammation and then resolution. They include squeezing out the lesions with forceps, piercing them with an orange
stick (preferably without phenol), and curettage. Liquid nitrogen may also be helpful.
These measures are fine for adults, but young children dislike them and it is reasonable to play for time using imiquimod or chlortetracycline cream, or instructing the mother carefully how to apply a wart paint once a week to lesions well away from the eyes.

Sometimes a local anaesthetic cream (EMLA; under polythene occlusion for

an hour, will help children to tolerate more attacking treatment. Sparse eyelid lesions can be left alone but patients with numerous lesions may need to be referred to an ophthalmologist for curettage. Common sense measures help to limit spread within the family.

Orf
Cause
Contagious pustular dermatitis is common in lambs.Its cause is a parapox virus that can be transmitted to those handling infected animals. on the hands of shepherds, of their wives who bottle-feed lambs, and of butchers, vets and meat porters.


Presentation and course
The incubation period is 5–6 days. Lesions single or multiple, start as small firm papules that change into flat-topped apparently pustular nodules with a violaceous and erythematous surround. The condition clears up spontaneously in a month.

Complications

• Lymphadenitis and malaise are common.• Erythema multiforme.
• ‘Giant’ lesions can appear in the immunosuppressed.

Differential diagnosis

Diagnosis is usually simple if contact with sheep is recognized. Milker’s nodules, a pox virus infection acquired from cow’s udders, can look like orf, as can staphylococcal furuncles.

Investigations

None are usually needed. If there is any doubt, the diagnosis can be confirmed by the distinctive electron microscopic appearance of the virus obtained from crusts.

Treatment

A topical antibiotic helps to prevent secondary infection;otherwise no active therapy is needed.

Acquired immunodeficiency syndrome (AIDS)

The AIDS epidemic was first recognized in the USA in 1981. The early cases were male homosexuals with pneumocystis pneumonia or Kaposi’s sarcoma and
immunosuppression. Later it became clear that the human immunodeficiency virus (HIV) could be acquired from contaminated body fluids, particularly semen and blood, in many ways, the importance of which varies from country to country. In the UK and the USA, for example, most cases have been homosexual or bisexual men; in parts of Africa, on the other hand, the disease is most often spread heterosexually. Other groups at high risk are intravenous drug abusers who share contaminated needles and syringes, and haemophiliacs who were given infected blood products. Up to a half of babies born to infected mothers will be infected transplacentally. The global epidemic is not slackening off though the pattern of transmission in industrialized nations is changing. Heterosexual transmission now accounts for 25–30% of new cases in Europe and the USA. In 1999, about 5.4 million people were newly infected with HIV.


Pathogenesis
The human immunodeficiency viruses, HIV-1 and HIV-2 (mainly in West Africa), are RNA retroviruses containing reverse transcriptase enzymes, which allow the viral DNA copy to be incorporated into the chromosomes of the host cell. Their main target is a subset of T lymphocytes (helper/inducer cells) that express glycoprotein CD4 molecules on their surface (p. 19). These bind to the surface envelope of the HIV. Viral replication within the helper/inducer cells kills them, and their depletion leads to the loss of cell-mediated immunity so characteristic of HIV infection. A variety of opportunistic infections may then follow.

Course

The original infection may be asymptomatic, or followed by a glandular fever-like illness at the time of seroconversion. After a variable latent phase, which may last several years, a persistent generalized lymphadenopathy develops. The term ‘AIDS-related complex’ refers to the next stage, in which many of the symptoms of AIDS (e.g. fever, weight-loss, fatigue or diarrhoea) may be present without the opportunistic infections or tumours characteristic of full-blown AIDS. Not all of those infected with HIV will develop AIDS but, for those who do, the average time from infection to the onset of AIDS is about 10 years. Once AIDS develops, if untreated, about half will die within 1 year and three-quarters within 4 years. Skin changes in AIDS
Skin conditions are often the first clue to the presence of AIDS. The following are important:

1 Kaposi’s sarcoma (Figs 14.32–14.34) is the initial presentation in a decreasing percentage of AIDS patients, particularly homosexual men. The lesions of classical Kaposi’s sarcoma are multiple purplish patches or nodules (see Fig. 19.49). In AIDS the lesions may be atypical, sometimes looking like bruises or pyogenic granulomata (p. 277). The diagnosis can easily be missed and the mouth must always be examined.

2 Seborrhoeic eczema and folliculitis (Fig. 14.35) are seen in at least 50% of patients, often starting at an early stage of immunosuppression. The underlying cause may be an overgrowth of Pityrosporum yeasts. An itchy folliculitis of the head, neck and trunk, and an eosinophilic folliculitis, possibly as a result of the multiplication of Demodex folliculorum, have also been described.

3 Skin infections aflorid, unusually extensive or atypical examples of common infections may be seen with one or more of the following: herpes simplex, herpes zoster, molluscum contagiosum, oral and cutaneous candida, tinea, pityriasis versicolor, scabies and staphylococci. Facial and perianal warts are common. Hairy leukoplakia (Fig. 14.36), often on the sides of the tongue, may be caused by proliferation of the Epstein–Barr virus. Bacillary angiomatosis may look like Kaposi’s sarcoma and is caused by the bacillus that causes cat-scratch fever. Syphilis can coexist with AIDS, as can mycobacterial infections.

4 Other manifestationsadry skin is common in AIDS; so is pruritus. Psoriasis may start or worsen with AIDS. Diffuse alopecia is not uncommon. Drug eruptions are often seen in AIDS patients.

Management

The clinical diagnosis of HIV infection is confirmed by a positive blood test for antibodies to the virus. Patients should be counselled before and after testing for HIV antibody. Sexual contacts of infected individuals should be traced. Modern drugs for HIV infections increase life expectancy, but are not ‘cures’ in the usual sense. They reduce the viral load but are expensive and sometimes toxic. Guidelines on how to use them change constantly, and so the drug treatment of HIV infections should be directed by specialists in the field, who will monitor the plasma viral load and CD4 count regularly (Table 14.1). Difficult decisions to be made include the timing of treatmentathe benefits of starting early have to be balanced against the risk of toxicityaand choosing the right drug combination of highly active antiretroviral treatment (HAART)a usually triple therapy with two nucleoside reverse transcriptase inhibitors plus either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The regimen will be changed if there is clinical or virological deterioration, or if the patient becomes pregnant, although the teratogenic potential of most of these drugs is still not known.

Table 14.1 Recommendations for starting highly active antiretroviral treatment (HAART) in the adult.
Disease stage Decision
Symptomatic Treat
Asymptomatic
CD4 200 106/L Treat
CD4 200–350 106/L Treatment generally
offered
CD4 350 106/L Defer treatment unless high
viral load


Treatment otherwise is symptomatic and varies according to the type of opportunistic infection detected. Prophylactic treatment against a number of life-threatening infections is also worthwhile, and prolongs life expectancy. Educating the public to avoid risky behaviour, such as unprotected sexual intercourse, is still hugely important.

Mucocutaneous lymph node syndrome (Kawasaki’s disease)

The cause may be a recent parvovirus infection. The disease affects young children whose erythema, although often generalized, becomes most marked in a glove and stocking distribution; it may be associated with indurated oedema of the palms and soles. Peeling around the fingers and toes is one obvious feature but is not seen at the start. Bilateral conjunctival injection and erythema of the lips, buccal mucosa and tongue (‘strawberry tongue’) are common. The episode is accompanied by fever and usually resolves within 2 weeks. Despite its name, not all patients have lymphadenopathy. The danger of this condition lies in the risk of developing myocarditis and coronary artery disease. The pathology is close to that of polyarteritis nodosa. Aspirin and intravenous gammaglobulin are the mainstay of treatment; both
should be given early in the disease and reduce the risk of coronary artery involvement.

Gianotti–Crosti syndrome

This is a rather uncommon reaction to an infection with hepatitis B virus in childhood. Small reddish papules erupt bilaterally over the limbs and face, and fade over the course of a few weeks. Jaundice is uncommon, although tests of liver function give
abnormal results.

Herpangina

This is an acute infectious illness, caused by group A Coxsackie viruses. The patient is usually a child with a fever, and a severe sore throat covered in many small vesicles, which rapidly become superficial ulcers. Episodes resolve in about a week.
Hand, foot and mouth disease This is usually caused by Coxsackie A16. Minor epidemics occur in institutions. The oral vesicles are larger and fewer than those of herpangina. The hand and foot lesions are small greyish vesicles with a narrow rim of redness around . The condition settles within a few days.

Measles

An incubation period of 10 days is followed by fever, conjunctival injection, photophobia and upper respiratory tract catarrh. Koplik’s spots (pinhead sized whitespots with a bright red margin) are seen at this stage on the buccal mucosa. The characteristic ‘net-like’ rash starts after a few days, on the brow and behind the ears,
and soon becomes extensive before fading with much desquamation. Prevention is by immunization with the combined MMR (measles/mumps/rubella) vaccine.


Rubella

After an incubation period of about 18 days, lymphadenopathy occurs a few days before the evanescent pink macular rash, which fades, first on the trunk,over the course of a few days. Rubella during the first trimester of pregnancy carries a risk of damage to the unborn child. Prevention is by immunization with the combined MMR vaccine.

Erythema infectiosum (fifth disease)

This is caused by the human parvovirus B19 and occurs in outbreaks, often in the spring. A slapped cheek erythema is quickly followed by a reticulate erythema of the shoulders. The affected child feels well, and the rash clears over the course of a few days.Other features, sometimes not accompanied by arash, include transient anaemia and arthritis.

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