What are the symptoms and clinical presentations of herpes zoster?

Herpes Zoster: Clinical Symptoms and Presentations

Herpes zoster typically presents with prodromal pain 24-72 hours before the rash appears, followed by a unilateral vesicular eruption in a dermatomal distribution that progresses from erythematous macules to papules and then vesicles over 4-6 days in immunocompetent patients. 1

Classic Presentation

• Prodromal phase: Pain, burning, or tingling sensation in the affected dermatome precedes skin findings by approximately 24-72 hours, often accompanied by malaise 1, 2

• Rash characteristics: Unilateral vesicular eruption strictly confined to one or more dermatomes, never crossing the midline 1

• Evolution of lesions: Erythematous macules progress to papules, then to vesicles containing clear fluid with high viral particle concentrations, which eventually burst to form shallow ulcers or erosions that crust over 1

• Duration: New lesions continue to erupt for 4-6 days in immunocompetent hosts, with total disease duration of approximately 2-4 weeks in otherwise healthy individuals 1, 3

• Associated symptoms: Local pain, pruritis, and possible inguinal lymphadenopathy (particularly in primary infection) 4

Pain Characteristics

• Severity: Trigeminal or ophthalmic involvement typically causes more severe pain compared to other dermatomes 1

• Temporal pattern: Acute pain during the rash phase may be followed by subacute herpetic neuralgia lasting up to 3 months, and potentially post-herpetic neuralgia (PHN) persisting for months to years 2

• Mechanisms: Pain results from increased excitability of primary afferent neurons after nerve damage (causing irritable nociceptors and central sensitization) and/or degeneration of nociceptive neurons leading to deafferentation with central hyperactivity 2

Atypical Presentations

• Nonspecific lesions: Some patients present without the characteristic vesicular appearance initially, making early diagnosis challenging 1

• Subtle manifestations: The rash may be atypical, localized, faint, or evanescent, particularly difficult to recognize in individuals with darker skin pigmentation 1

• Zoster sine herpete: Pain in a dermatomal distribution without visible rash, which can be mistaken for other conditions like Bell's palsy when involving the facial nerve 3

• Immunocompromised patients: May develop extensive, deep, nonhealing ulcerations with persistent viral replication rather than typical self-limited vesicles, most commonly in those with CD4+ counts <100 cells/µL 4, 5

Serious Complications

• Post-herpetic neuralgia (PHN): The most common and debilitating complication, characterized by chronic pain persisting beyond 3 months after rash resolution 6, 7

• Ophthalmic zoster: Involvement of the ophthalmic division of the trigeminal nerve can lead to ocular complications including keratitis and, if untreated, potential vision loss 3

• Ramsay Hunt syndrome: Reactivation of varicella zoster virus involving the facial nerve, presenting with facial paralysis, ear pain, and vesicles in the ear 3

• Delayed contralateral hemiparesis: A rare complication of ophthalmic zoster that may present as stroke, temporally remote from the initial zoster episode 3

• Secondary infections: Chronic ulcerations may develop bacterial and fungal superinfections, particularly in immunocompromised hosts 1

Diagnostic Considerations

• Laboratory confirmation: Tzanck smear showing giant cells can be diagnostic for herpesvirus infection 1

• Definitive testing: Vesicle fluid specimens can be obtained for immunofluorescence antigen testing, culture, or PCR (most sensitive method) to confirm diagnosis 1, 5

• When to test: Consider diagnostic testing if presentation is atypical, patient is immunocompromised, or to differentiate from conditions like impetigo 1

• Risk factor screening: Screen for HIV infection, diabetes, malignancy, or immunosuppressive medications, as these increase both risk and severity of disease 1

High-Risk Populations

• Age-related risk: Incidence increases sharply in individuals over 50 years of age due to waning cell-mediated immunity 7, 8

• Immunocompromised patients: Recipients of blood, bone marrow, or solid organ transplants; HIV-infected individuals; and those on immunosuppressive therapy are at significantly higher risk for developing herpes zoster and experiencing more severe disease with atypical presentations 1, 6

• Mortality considerations: Lack of rash or late-onset rash has been associated with delays in diagnosis and increased mortality in some cases 1

Common Diagnostic Pitfalls

• Misdiagnosis as other conditions: Herpes zoster in the genital region may be misdiagnosed as genital herpes simplex virus infection due to similar vesicular appearance 5

• Confusion with non-infectious causes: Inflammatory conditions such as Crohn's disease or fixed drug eruption may mimic zoster and require laboratory differentiation 4

• Delayed recognition: Absence of characteristic pain or atypical rash presentation can lead to diagnostic delays, particularly problematic in immunocompromised patients where early treatment is critical 1