Varicella zoster with erythema multiforme in a young girl: a rare association.

Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder regarded as a hypersensitivity reaction which is triggered by various factors like infection, drugs, and food. Infectious agents are considered to be a major cause of EM other than idiopathic cause. A young girl presented with fluid-filled lesions all over the body of 3 days duration with history of similar lesions with fever in her sibling 2 weeks prior to admission. This was followed by large fluid-filled lesions with halo 3 days thereafter over the trunk, extremities suggesting target lesions of EM. The diagnosis was confirmed by cytology and positive serology. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence in childhood. VZV as an etiology of EM in a young girl has not been reported so far. This case was reported for its rare association of EM and varicella zoster and also for its rare presentation in a young girl.

What was known?

Erythema multiforme, a mucocutaneous hypersensitivity reaction which is triggered by various factors.

Introduction

Erythema multiforme (EM) was first described by Ferdinand von Hebra in 1866.[1] EM is an acute, self-limited, and mucocutaneous disorder considered to be a hypersensitivity reaction associated with certain infections and medications.[2] EM can occur in patients of all ages, but more commonly seen in adults.[1] Previously, the condition was thought to be part of a clinical spectrum of disease that included erythema minor, erythema major (often equated with Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); with erythema minor being the most mild and TEN the most severe. EM minor represents a localized eruption of the skin with minimal or no mucosal involvement. The papules evolve into pathognomonic target or iris lesions that appear within a 72-hour period and begin on the extremities and heals in period of one week.[2]

List of etiologic factors have been reported to cause EM which may be induced by medications, but infectious agents are also considered to be a major cause of EM. Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50% of cases.[13] Other causes are infection with Mycoplasma pneumoniae, vaccinia, or varicella zoster virus (VZV); immunizations; and a wide variety of physical agents.[4] To the best of our knowledge, few cases of VZV infection have been reported in association with EM.[345]

Case Report

A 14-year-old girl aged 14 years presented with fluid-filled lesions followed by fever with history of chicken pox in her younger sister 2 weeks prior to admission that was resolved by treating with oral acyclovir. Three days later mild pruritic reddish raised lesions were seen that developed into larger fluid-filled lesions all over the body mainly involving upper extremities, trunk, face, and scalp. These oozy fluid filled lesions evolved to form crust in duration of 4-5 days. There was no history of drug intake or having applied any medication prior to the onset of these lesions.

On examination, multiple discrete vesicles on an erythematous base were seen distributed all over the body. Multiple symmetrically distributed round lesions with central blister surrounded by erythematous halo (‘Target lesions’) were seen over the trunk, extremities, face, and scalp. Few vesicles were present on genitalia. No oral lesions were seen. Apart from cutaneous findings, the physical examination was normal [Figures 1–4].

Figure 1

Target lesion with vesicles over lower abdomen

Figure 4

Varicella lesions over forearm

Drying target lesions with vesicles

Target lesions with vesicles over lower limbs

Tzanck smear showed multinucleated giant cells [Figure 5]. Specimen sent for the detection of varicella zoster DNA by polymerase chain reaction (PCR) technique confirmed the diagnosis of varicella. A diagnosis of EM with varicella was done based on the clinical manifestation supported by PCR examination. Patient received oral acyclovir 800 mg four times a day for 7 days. Vesicular lesions resolved gradually over the next 7 days.

Figure 5

Multinucleated giant cell on Tzanck smear (Giemsa stain)

Discussion

EM has multiple etiologies of which viral infection is a well known entity. HSV infection is a predominant preceding event in individuals that experience recurrent episodes of EM, and such individuals are labeled as having herpes-associated EM (HAEM).[6] To the best of our knowledge, few cases of VZV infection have been reported in association with EM as shown in the following table [Table 1].[4]

Table 1

Characteristics of reported patients with vericella zoster virus infection associated with erythema multiforme

However, EM is currently more common in younger males (male-to-female ratio, range of 3:2 to 2:1).[7] Previous history of EM and male sex has also been reported as risk factors to development of EM. The condition is rare in children younger than 3 years and in adults older than 50 years.[8] A relationship exists between HLA types: A33, B35, B62 (B15), DR4, DQB1*0301, DQ3, and DR53 and recurrent EM. In particular, HLA-DQ3 is especially related to recurrent EM and may be a helpful marker for distinguishing HAEM from other cutaneous diseases.[9]

The pathogenesis of EM with herpes virus association is consistent with a delayed hypersensitivity reaction. The disease begins with the transport of the viral DNA fragments by circulating peripheral blood mononuclear CD34+ cells (Langerhans cell precursors) to keratinocytes, which leads to the recruitment of herpes virus-specific CD4+ TH1 cells. The inflammatory cascade is initiated by interferon-γ (IFN-γ), which is released from the CD4+ cells in response to viral antigens, and immune mediated epidermal damage begins subsequently.[10]

Beneficial effects with hemodialysis, plasmapheresis, cyclosporin, immunoglobulin, levamisole, thalidomide, dapsone, and cyclophosphamide have been documented in case reports.[13]

Prophylaxis for recurrence of HAEM should be considered in case of recurrences more than 5 attacks per year. Low-dose acyclovir (200 mg QD to 400 mg BID) can be effective for recurrence of HAEM. Prophylaxis may be required for 6-12 months or longer; if unresponsive, continuous therapy with valacyclovir (500 mg BID) has been reported to be effective.[7] We suspect that Varied morphology of the eruption in EM may mask the diagnosis of chicken pox, possible presence of VZV infection should be considered.

What is new?

VZV as an etiology of EM in a young girl has not been reported so far.