What is the frequency of Herpes Simplex Virus (HSV) appearance in patients with pemphigus?

Frequency of HSV in Pemphigus Patients

Herpes simplex virus (HSV) infection occurs in approximately 38% of patients with pemphigus vulgaris, primarily as a complication of immunosuppressive therapy rather than as a triggering factor for the disease. 1

Prevalence and Relationship

• HSV is not likely to be an etiologic trigger for pemphigus, but rather appears as a frequent complication of immunosuppression 2
• In a recent study (2023), HSV infection was confirmed in 23 out of 60 (38.33%) patients with pemphigus vulgaris 1
• HSV positivity is significantly more common in patients already receiving corticosteroid treatment compared to untreated patients 2
• The prevalence of HSV in pemphigus may be underestimated as it can clinically mimic pemphigus exacerbations 3

Clinical Presentation of HSV in Pemphigus

HSV infection in pemphigus patients presents with distinctive clinical features that differ from typical pemphigus lesions:

Independent Predictors of HSV in Pemphigus (Multivariate Analysis)

• Hemorrhagic crusts (p=0.015) 1
• Linear erosions (p=0.008) 1

Additional Clinical Markers (Univariate Analysis)

• Fissures (p=0.001) 1
• Erosions with angulated margins (p=0.024) 1
• Raised erythrocyte sedimentation rate (p=0.015) 1
• Male sex (p=0.03) 1
• Painful nature of eruptions (highly suggestive) 3
• Vesicles grouped in bouquets 3

Timing and Risk Factors

• HSV infections typically appear after initiating immunosuppressive therapy:
  • Usually within 15 days to 1 month after starting corticosteroids (1-1.5 mg/kg/day) 3
  • Risk increases when corticosteroids are combined with other immunosuppressants (azathioprine, cyclophosphamide) 3
• Five out of eight HSV-negative pemphigus patients became HSV-positive within two weeks of starting intensive immunosuppressive therapy 2

Clinical Significance

• HSV can cause relapse, exacerbation, and treatment resistance in pemphigus vulgaris patients 1
• HSV infection should be suspected in cases of:
  • Unexpected exacerbation of pemphigus 3
  • Lack of improvement despite adequate immunosuppressive therapy 4
  • Particularly painful lesions 3
• In rare cases, HSV infection in pemphigus can be fatal due to severe herpetic hepatitis and disseminated intravascular coagulation 3

Diagnosis

• PCR testing is the most sensitive method for detecting HSV in pemphigus lesions 4
• Conventional techniques may fail to identify HSV in pemphigus lesions 4
• Cytological swabs from oral erosions are particularly useful for PCR testing 4
• Both HSV-1 and HSV-2 can be detected in pemphigus patients 3

Management

• Prompt antiviral therapy with acyclovir is recommended when HSV is detected 3
• Cure is typically achieved within 5-20 days with systemic acyclovir 3
• Recurrence of HSV infection can occur in pemphigus patients (reported in approximately 2 out of 6 cases in one study) 3

Clinical Pitfalls

• HSV infection can be mistaken for pemphigus relapse 3
• Failure to recognize HSV can lead to inappropriate escalation of immunosuppression, potentially worsening the infection 3
• The painful nature of lesions should raise suspicion for HSV rather than pemphigus alone 3