What is the diagnostic utility of a Tzanck smear for herpes simplex virus, varicella‑zoster virus, cytomegalovirus, molluscum contagiosum, and autoimmune bullous diseases, and what are its limitations and subsequent management recommendations?

Tzanck Smear in Various Infections

Primary Recommendation

The Tzanck smear should not be relied upon for diagnosis of herpes simplex virus or varicella-zoster virus infections due to low sensitivity and specificity, and must be replaced by nucleic acid amplification tests (NAATs/PCR) when available. 1, 2

Diagnostic Performance by Infection Type

Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV)

Critical Limitation: The Tzanck smear cannot differentiate between HSV and VZV infections, even when positive. 1, 3

Performance Characteristics:

• Sensitivity: 80-84.7% for multinucleated giant cells in herpetic infections (when performed by experienced operators in vesicular stage lesions). 3, 4
• Specificity: Approximately 90% when investigators are experienced. 3
• Major drawback: Sensitivity drops dramatically in ulcerative or crusted lesions compared to fresh vesicles. 5

Preferred Alternative Testing:

• NAATs/PCR are the gold standard with sensitivity and specificity both approaching 100%, and can detect VZV DNA even in crusted lesions. 1, 2
• PCR provides HSV typing (HSV-1 vs HSV-2), which is clinically essential since 12-month recurrence rates differ dramatically: HSV-2 (90%) vs HSV-1 (55%). 6
• Viral culture has been the cornerstone of diagnosis but is less sensitive than NAAT, particularly for recurrent or ulcerative lesions. 1, 6

Autoimmune Bullous Diseases (Pemphigus Group)

The Tzanck smear has moderate utility for pemphigus disorders but should not replace definitive testing:

• Sensitivity: 80.70-81.01% when compared to histopathology or anti-desmoglein antibodies. 7
• Specificity: 68.18-87.50% depending on comparison method. 7
• Key finding: Acantholytic cells (both complete and incomplete forms), with incomplete cells predominating in 60.32% of cases. 7
• Diagnostic features: Rounding is the most consistent feature, followed by nuclear enlargement; streptocytes, dyskeratosis, and tadpole cells may also be present. 7

Important caveat: Acantholytic cells are not specific to pemphigus and can also appear in spongiotic dermatitis and genodermatoses. 8

Molluscum Contagiosum

• The Tzanck smear can identify molluscum bodies (Henderson-Patterson bodies) in molluscum contagiosum cases. 7
• However, clinical diagnosis is usually straightforward, and Tzanck smear is rarely necessary for this condition.

Cytomegalovirus (CMV)

• No evidence supports the use of Tzanck smear for CMV diagnosis in the provided guidelines.
• CMV diagnosis requires specific viral culture, antigen detection, or PCR testing. 9

Technical Considerations for Optimal Tzanck Smear Performance

Specimen Collection Technique:

• Sample from the roof of fresh vesicles, not the floor, as this increases detection of large multinucleated giant cells by 2.0-fold. 5
• Open vesicles with a sterile needle first, collect vesicular fluid, then vigorously swab the base to obtain epithelial cells. 6
• Use cotton-wool or Dacron swabs; avoid calcium alginate swabs which interfere with viral recovery. 6

Timing Considerations:

• Collect specimens as early as possible in the disease course, as vesicular lesions yield higher positivity than ulcerative lesions. 6
• First episode lesions are more likely positive than recurrent lesions. 6

Staining Methods:

• May-Grünwald-Giemsa staining is standard. 4
• Quick staining with Hemacolor or Diff-Quik can be performed within one minute. 3

Clinical Management Algorithm

When Herpetic Infection is Suspected:

1. Do not delay antiviral therapy (aciclovir, valaciclovir, or famciclovir) while awaiting diagnostic confirmation when clinical suspicion is strong. 2
2. Order NAAT/PCR as first-line diagnostic test from vesicular fluid or lesion base swab. 2, 6
3. Request HSV typing (HSV-1 vs HSV-2) to guide prognosis and counseling. 6
4. Tzanck smear may be used only when NAAT/PCR is unavailable and immediate bedside diagnosis could alter management, understanding its limitations. 3, 8

When Autoimmune Bullous Disease is Suspected:

1. Tzanck smear can provide rapid preliminary information to support early treatment initiation. 7, 8
2. Always confirm with skin biopsy for histopathology and direct immunofluorescence. 8
3. Obtain anti-desmoglein antibody testing for definitive diagnosis. 7

Common Pitfalls to Avoid

• False negatives occur frequently with ulcerative, crusted, or healing lesions. 5
• Dyskeratotic keratinocytes in vacuolar interface dermatitis can be mistaken for acantholytic cells. 8
• Acantholytic cells are not pathognomonic for pemphigus and appear in multiple conditions. 8
• Operator experience significantly affects sensitivity and specificity. 3, 4
• Cannot distinguish HSV from VZV, requiring additional testing for specific diagnosis. 1, 3