Etiology and pathogenesis

Herpes simplex virus infection is caused by two types of DNA viruses namely HSV 1 and HSV 2. Characteristically, HSV 1 is responsible for infections involving the oropharyngeal regions, dermatitis and meningoencephalitis (infections above the waist) and HSV 2 is responsible for anogenital infections (infections below the waist). However, changing sexual practices have shown that these viruses may not necessarily be responsible for infections of specific sites.

In contrast to other viruses HSV needs physical contact to transfer infection. The incubation period ranges from 2 days to 3 weeks. After the primary infection the virus hides within the trigeminal ganglia and becomes activated when the environment is conducive for viral replication. Approximately 90% of USA population is seropositive for antibodies to HSV. Of this group only 1% exhibit primary herpetic infections and 30–40% demonstrate recurrent infections. Primary HSV infections are usually seen after 6 months of age and peak at about 2–3 years of age.

Other specific HSV infections include herpetic whitlow, herpetic gladiatorum, herpetic meningoencephalitis, herpetic conjunctivitis, herpetic eczema (Kaposi’s varicelliform eruption) and disseminated herpes simplex of newborn.

Clinical features

Investigations

Typical clinical features will usually suffice to make a clinical diagnosis. However for definitive diagnosis cytological smears, antibody titers and viral isolation can be used.

Cytological smear requires deroofing a fresh vesicle, followed by scraping of the base of the lesion and the smear made should be stained with Papanicolaou’s, Wright’s or Giemsa’s stain.

The characteristic findings include the presence of multinucleated giant cells and intranuclear viral inclusion bodies such as Lipschutz bodies or Cowdry Type A (ovoid, amorphous, eosinophilic bodies that exhibit peri inclusion halo that is caused by the peripheral displacement of the nucleolus and the nuclear chromatin). The cells exhibit ballooning degeneration of the nucleus.

On biopsy the microscopic features include an ulcerated epithelium with large keratinocytes showing glassy giant marginated nuclei (Tzanck cells) (Figures 1 and 2).

Alternatively viral isolation can be done. It is one of the most definitive methods of identifying HSV.

Serological tests can be used to detect antibodies in patient suffering from primary HSV. For the test, blood sample should be taken in the initial 3 days of an acute infection. Alternatively a convalescent blood sample can be obtained 4 weeks after the primary infection. It is believed that the antibody titer should increase by four times in convalescent serum sample for the diagnosis of the primary infection.

Differential diagnosis

Treatment

The aims of managing HSV infections are to inhibit autoinoculation and transmission. The management is targeted at symptomatic relief. Topical and systemic antivirals like acyclovir can be used (Table 3).

To be effective all treatment should be started within 72 hours of initial disease presentation. Patient compliance is shown to be better with fewer and shorter doses (Whitley, 2006).

Prognosis

The main question arises should you treat these patients when they have recurrent lesions. Universal precautions including use of gloves enable us to do proceed with treatment. If the lesions are oozing and will transfer virus to other sites and patient has no emergency it is advisable to postpone treatment. If in an emergency application of rubber dam may help in decreasing transmission of virus to other sites.

Herpes simplex virus infections are described in detail in Chapter 4 on Bacterial, Viral and Fungal Infections.

Clinical features

Investigations

Cytological smears derived from the vesicles reveal multi-nucleated giant cells along with intranuclear inclusion bodies. PCR and direct immunofluorescence assay are more effective in diagnosing HZV infections.

Differential diagnosis

Recurrent herpetic lesions and aphthous ulcers should be considered in the differential diagnosis of intraoral lesions.

Treatment and prognosis

In healthy patients if the diagnosis occurs within 72 hours of initiation of the disease a course of acyclovir or valacyclovir can be administered. If the patient is seen later during the course of the disease symptomatic relief in the form of magic mouthwash can be prescribed. In immunosuppressed patients a prescription of acyclovir or valacyclovir can be administered. It is some belief that a prescription for antiviral and corticosteroid therapy prevents postherpetic neuralgia.

Etiology

Enteroviruses are known to cause HFM disease. The enteroviruses that have been implicated are Coxsackie virus serotype A 16, Coxsackie virus serotype A 4 to 7, 9, 10 and Coxsackie virus serotype B 1 to 3 and 5. Asia Pacific region including regions like Singapore, Japan, Indonesia, Malaysia and Taiwan in the 1970s reported severe forms of HFM disease resulting in a widespread epidemic. The cause for this epidemic was Enterovirus-71 A, B, C (EV 71). The EV-71 apart from causing HFM disease can also cause flaccid paralysis, myocarditis, pulmonary hemorrhage, encephalitis and meningitis.

Deshpande et al (2003) isolated a strain of EV-71 from the stool of a child suffering from acute flaccid paralysis following administration of oral polio vaccine. They termed this isolated strain as EV 71 D genotype.

Sasidharan et al (2005) studied 81 children (age group of 7 months to 8 years) who presented with papulovesicular exanthems in Calicut, India. In their study 19 children showed a significant rise in the titers of IgM antibody against EV-71.

Infection usually occurs by the fecal-oral route, leading to viremia and invasion of the skin and mucosa. The incubation period is approximately 3–7 days.

Clinical features

Patients usually present with prodromal symptoms such as low-grade fever, malaise, anorexia, myalgia, headache, cough, rhinorrhea and sore throat. The skin of the hands and feet along with the oral mucosa are involved. The oral mucosa and the hand are almost always affected.

The skin lesions are characterized by the presence of numerous erythematous macules in the initial stage. As the disease progresses vesicles begin to appear in the macules which subsequently heal without crusts in about 10 to 14 days.

The common sites of involvement are the palms and fingers of the hand, and soles and toes of the feet. Other sites that are less commonly affected are the trunk, external genitalia and the buttocks.

Oral manifestations

The oral lesions usually occur before the skin lesions. Multiple vesicles and ulcers may be seen affecting any part of the oral mucosa. However the common sites that are involved include the tongue, buccal mucosa and hard palate. Patients usually complain of pain, sore throat and dysphagia. Oral lesions usually heal without complications in about 7 days time.

The oral manifestations of HFM disease mimic lesions of herpangina, acute herpetic gingivostomatitis, recurrent herpetiform and minor aphthous ulcerations and erythema multiforme.

Management

The disease is self-limiting and needs to be symptomatically managed. Systemic antipyretics (paracetamol suspension or tablet), topical analgesic mouthrinse (benzydamine hydrochloride) and topical anesthetic agents (2% lignocaine gel) are effective in the management of fever and sore mouth.

Clinical features

Compared to hand, foot and mouth disease the disease process is usually mild and patients may not exhibit overt prodromal symptoms. Patients may present with mild rise in temperature, malaise, anorexia, abdominal pain, sore throat and cervical lymphadenopathy.

Oral manifestations

Oral manifestations are very typical of this condition. Multiple minute vesicles and ulcers roughly measuring 1–2 mm in diameter are seen. The ulcers are surrounded by an erythematous halo. These lesions are typically confined to the posterior part of the oral cavity such as the faucial pillars, tonsillar region, posterior pharyngeal region, soft palate and uvula. Very rarely the posterior parts of the buccal mucosa and tongue are involved. Patients may complain of sore throat and difficulty in swallowing.

Management

Herpangina is a self-limiting disease. The fever associated with this condition usually subsides within 3–4 days. The oral ulcers heal within a week. The condition can be managed symptomatically with antipyretics and analgesic/ anesthetic mouthrinses.

Clinical features

Dermatitis herpetiformis usually affects individuals in the 2nd and 3rd decade of life. Dermal lesions are characterized by blisters over an erythematous or urticarial base. The lesions are pruritic.

The common sites of involvement include the knees, elbows, scalp, back and buttocks. It is believed that about 10% of the patients present with symptoms of celiac disease. DH is believed to be associated with some of the autoimmune and connective tissue diseases such as Type I diabetes mellitus, pernicious anemia, autoimmune thyroiditis, Sjogren’s syndrome, lupus erythematosus, sarcoidosis, scleroderma and psoriasis. DH has also been frequently associated with hypopigmentation.

Oral manifestations

Dermatitis herpetiformis can involve any part of the oral mucosa. It manifests as multiple vesicles are bullae. These fragile vesicles rupture immediately to form shallow painful ulcers.

Investigations

Histopathologically, presence of microabscesses in the dermal papillae and subepithelial blister formation are some of the findings associated with DH. The characteristic finding in DH is the presence of eosinophilia.

Direct immunofluorescence test reveals the presence of antibodies IgA, IgM and IgG at the junction of the dermis and epidermis.

Dietrich et al (1999) demonstrated that the level of immunoglobulin A autoantibodies to endomysium in patients with DH was significantly elevated.

Patients exhibit sensitivity to halogens.

Management

Dermatitis herpetiformis usually runs a prolonged course and sometimes persists for life. Patients are advised to avoid glute/>