What is the most likely diagnosis for a patient presenting with a painful unilateral vesicular rash confined to a single dermatome?

Herpes Zoster (Shingles)

The most likely diagnosis is herpes zoster (shingles), which characteristically presents as a painful unilateral vesicular rash confined to a single dermatome. 1, 2

Clinical Presentation

Herpes zoster results from reactivation of varicella-zoster virus (VZV) that remained dormant in dorsal root ganglia following primary chickenpox infection. 1

Classic Features

• Prodromal pain typically precedes the rash by 24-72 hours, manifesting as burning, itching, tingling, or paresthesia localized to a single dermatome before any visible skin changes appear 2

• The rash is unilateral and follows a dermatomal distribution, progressing from erythematous macules to papules and then to vesicles 1, 2, 3

• Lesions continue to erupt for 4-6 days in immunocompetent hosts, with total disease duration of approximately 2 weeks 2

• The vesicles are thin-walled and frequently coalesce before forming ulcers 4

Distinguishing from Other Conditions

• Herpes simplex virus (HSV) lacks the unilateral dermatomal distribution and typically produces clustered vesicles confined to localized areas (oral or genital mucosa) 4

• HSV recurs at the same anatomical site repeatedly, whereas herpes zoster does not show consistent dermatomal recurrence 4

• Both HSV and VZV progress through identical morphologic stages (macules → papules → vesicles → pustules → ulcers), making laboratory confirmation essential when clinical features are atypical 4

Diagnostic Confirmation

Clinical diagnosis is sufficient for typical presentations in immunocompetent patients, but confirmatory testing should be obtained in specific situations 2:

• Atypical presentations (nonspecific lesions, faint or evanescent rash, absence of characteristic pain) 2
• Immunocompromised patients (HIV, active chemotherapy, organ transplant recipients, chronic immunosuppression) 2
• Diagnostic uncertainty or need to differentiate from impetigo 2

Preferred Diagnostic Tests (When Indicated)

• Polymerase chain reaction (PCR) of vesicle fluid is the most sensitive and specific test, approaching 100% sensitivity and specificity, and can detect viral DNA even in crusted lesions 2

• Direct immunofluorescence (DFA) antigen testing of vesicle fluid provides rapid confirmation and is an accepted alternative when PCR is unavailable 2

• Tzanck smear demonstrates multinucleated giant cells, confirming herpesvirus infection but cannot differentiate VZV from HSV 1, 2

• Serologic testing (VZV IgG/IgM) does not aid in diagnosing active herpes zoster and should not be ordered 2

Risk Factors

• The lifetime risk of herpes zoster is 20-30% in the general population, with increased risk in elderly and immunocompromised populations 1

• Patients with conditions that decrease cell-mediated immunity are 20 to 100 times more likely to develop herpes zoster 3

• Recipients of blood, bone marrow, or solid organ transplants are at higher risk for developing herpes zoster 2

Common Pitfalls

• Do not dismiss the diagnosis based on absence of pain—some patients present without characteristic pain, particularly in atypical presentations 2

• Do not wait for laboratory confirmation to initiate treatment in immunocompromised patients with suspected herpes zoster 2

• In patients with darker skin pigmentation, the rash might be difficult to recognize, requiring heightened clinical suspicion 2