Vesiculobullous Diseases: Etiology and Pathogenesis

Vesiculobullous Diseases

• Etiology and Pathogenesis
  • Vesiculobullous diseases can be caused by viral, immunologic, and hereditary factors
  • Viral diseases include herpes simplex, varicella-zoster, and hand-foot-and-mouth disease
  • Immunologic diseases include pemphigus vulgaris, mucous membrane pemphigoid, and dermatitis herpetiformis
  • Hereditary diseases include epidermolysis bullosa

Herpes Simplex Infection

• Etiology and Pathogenesis
  • Herpes simplex virus (HSV) is a common cause of vesiculobullous diseases
  • HSV is transmitted through direct contact with an infected individual
  • The virus infects epithelial cells and causes the formation of vesicles and ulcers
• Primary Herpes Simplex Infection
  • Occurs in individuals who have not been previously exposed to the virus
  • Characterized by a vesiculoulcerative eruption in the oral and perioral tissues
  • May be accompanied by systemic signs and symptoms such as fever, malaise, and cervical lymphadenopathy
  • Lesions heal without scarring in 7-10 days
• Secondary Herpes Simplex Infection
  • Occurs in individuals who have been previously infected with the virus
  • Characterized by a recurrence of lesions at or near the same site as the primary infection
  • Lesions are typically confined to the lips, hard palate, and gingiva
  • May be accompanied by prodromal symptoms such as tingling, burning, or pain
  • Lesions heal without scarring in 1-2 weeks
• Herpetic Whitlow
  • A primary or secondary HSV infection involving the finger(s)
  • Typically occurs in individuals who have been in physical contact with an infected individual
  • Characterized by pain, redness, and swelling, with vesicles or pustules that eventually break and become ulcers

Histopathology

• Microscopic Features
  • Intraepithelial vesicles containing exudate, inflammatory cells, and characteristic virus-infected epithelial cells
  • Virus-infected keratinocytes contain one or more homogeneous, glassy nuclear inclusions### Herpes Simplex Virus (HSV)
• HSV1 and HSV2 have identical microscopic appearances and cannot be differentiated microscopically
• After several days, herpes-infected keratinocytes cannot be demonstrated in biopsy or cytologic preparations
• Differential diagnosis of HSV infection includes aphthous stomatitis, streptococcal pharyngitis, erythema multiforme, and acute necrotizing ulcerative gingivitis (ANUG)
• Tzanck smear or preparation is helpful in diagnosing HSV infection only if it is positive

Treatment of HSV Infection

• Systemic antiviral agents, including acyclovir and valacyclovir, are effective in controlling primary genital herpes and primary oral herpetic gingivostomatitis
• Supportive therapy is an essential component of any primary herpes simplex regimen
• Topical acyclovir has been advocated for the treatment of secondary or recurrent herpes, but its effectiveness is limited
• Topical n-docosanol (10%) has been used effectively, but randomized clinical trials are lacking

Varicella-Zoster Virus (VZV) Infection

• Primary VZV infection is known as varicella or chickenpox, while secondary or reactivated disease is known as herpes zoster or shingles
• VZV is structurally similar to HSV, with a DNA core, protein capsid, and lipid envelope
• Microscopically, VZV and HSV infections show similar characteristics, including a cutaneous or mucosal vesiculo-ulcerative eruption

Pathogenesis of VZV Infection

• Varicella is believed to be transmitted predominantly through direct contact by contaminated droplets from skin lesions or by the inhalation of aerosolized virus
• The condition is very contagious and is known to spread readily from person to person
• After a 2-week incubation period, virus proliferates within macrophages, with subsequent viremia and dissemination to the skin and other organs

Clinical Features of VZV Infection

• Varicella is characterized by a rash that involves primarily the trunk, head, and neck, and becomes vesicular and ulcerative
• Fever, chills, malaise, and headache may accompany the rash
• Oral mucous membranes may be involved, showing multiple shallow ulcers that are preceded by evanescent vesicles

Herpes Zoster (Shingles)

• Herpes zoster is essentially a condition of the older adult population and of individuals who have compromised immune responses
• The incidence of herpes zoster infection increases with age, reaching approximately 10 cases per 100,000 patient-years by age 80
• The sensory nerves of the trunk and head and neck are commonly affected, resulting in a unilateral maculopapular rash that becomes vesicular and ulcerative

Hand-Foot-and-Mouth Disease (HFM)

• HFM disease is a common, moderately contagious viral infection that usually is caused by Coxsackie type A16 or enterovirus 71
• The virus is transferred from one individual to another through direct contact with nasal secretions, saliva, blister fluid, or via fecal-oral contamination
• The virus exhibits a predilection for mucous membranes of the mouth and cutaneous regions of the hands and feet, as well as the buttocks
• Clinical features of HFM disease include low-grade fever, malaise, lymphadenopathy, and sore mouth, with multiple maculopapular lesions on the feet, toes, hands, and fingers### Vesiculobullous Diseases

Hand-Foot-and-Mouth Disease

• Caused by Coxsackie virus A1-6, A8, A10, A22, B3, and possibly others
• Transmitted through contaminated saliva and occasionally through contaminated feces
• Symptoms: malaise, fever, dysphagia, and sore throat
• Intraorally, a vesicular eruption appears on the soft palate, faucial pillars, and tonsils
• Duration: 4 to 6 days
• Differential diagnosis: primary herpetic gingivostomatitis, varicella, and streptococcal pharyngitis

Herpangina

• Caused by Coxsackie virus A1-6, A8, A10, A22, B3, and possibly others
• Symptoms: malaise, fever, dysphagia, and sore throat
• Intraorally, a vesicular eruption appears on the soft palate, faucial pillars, and tonsils
• Duration: 4 to 6 days
• Differential diagnosis: primary herpetic gingivostomatitis, varicella, and streptococcal pharyngitis

Measles (Rubeola)

• Caused by measles virus (RNA-enveloped virus, member of the paramyxovirus family)
• Spread through airborne droplets
• Incubation period: 7-21 days
• Contagious: 4 days before until 4 days after the onset of the body rash
• Symptoms: fever, malaise, coryza, conjunctivitis, photophobia, and cough
• Pathognomonic Koplik's spots appear on the buccal mucosa (small, erythematous macules with white necrotic centers)
• Rash: maculopapular, initially affects the head and neck, followed by the trunk and extremities
• Complications: encephalitis and thrombocytopenic purpura

German Measles (Rubella)

• Caused by an unrelated virus of the togavirus family
• Shares some clinical features with measles, but with milder symptoms
• Can cause congenital defects in a developing fetus
• Vaccine: MMR vaccine (live attenuated viruses of measles, mumps, and rubella)

Pemphigus Vulgaris

• Autoimmune mucocutaneous disease characterized by intraepithelial blister formation
• Results from a breakdown or loss of intercellular keratinocyte adhesion
• Causes: circulating autoantibodies of the IgG type that are reactive against desmoglein 3
• Symptoms: painful ulcers, preceded by flaccid and short-lived intraoral vesicles and bullae
• First signs of the disease appear in the oral mucosa in approximately 70% of cases
• Ulcers range in appearance from small aphthous-like lesions to large, irregular map-like lesions
• Treatment: immunosuppressives, biologic agents, and IVIg
• High mortality when untreated