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Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr virus reactivation: Exploration of a possible link

  • Author(s): Scheinfeld, Noah
  • et al.
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Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr virus reactivation: Exploration of a possible link
Noah Scheinfeld
Dermatology Online Journal 13 (3): 13

Columbia University, New York.Scheinfeld@earthlink.net

Abstract

Unilateral laterothoracic exanthem (ULE) was first described in 1962 in the United States and comprehensively elaborated in 1992. Although ULE most commonly occurs in children, ULE can occur in adults. ULE may or may not be preceded by a viral prodrome and is marked by coalescing erythematous papules predominately on one side of the body. ULE usually lasts 4-6 weeks but can last as little as 2 weeks. It has inconsistently been linked to viral infection, in particular parvovirus B-19. I note ULE in an adult with concurrent reactivation of Epstein Barr virus (EBV) that lasted 4 weeks. The role of the reactivation of EBV in human disease and ULE is explored.


Unilateral laterothoracic exanthem (ULE) (also termed asymmetric periflexural exanthem of childhood) was first described in 1962 in the United States and comprehensively elaborated in 1992 [1, 2, 3, 4, 5, 6]. It usually manifests as unilateral erythema without systemic symptoms. ULE has been linked to viral infection, in particular parvovirus B-19. While ULE most commonly occurs in children, ULE can occur in adults.


Clinical synopsis


Figure 1

A 35 year-old woman presented with an asymptomatic 2-week history of a unilateral erythematous eruption on her right flank (Fig. 1) without palpable lymph nodes. Skin biopsy and viral testing were performed. The skin biopsy showed a superficial and deep infiltrate of lymphocytes, and a lymphocytic infiltrate surrounding blood vessels and eccrine ducts (Figs. 2 and 3). Viral titers for demonstrated an EBV early antigen D Elisa Value (EV) of 81.9 (normal range 0-19.9), an EBV capsid antibody IgM EV of 2.8 (normal range 0-19.9), an EBV capsid antibody IgG EV of >20 (normal range 0-19.9) (positive), an EBV nuclear antigen EV of 87 (normal range 0-19.9) and a Parvovirus B-19 Index EV of <0.9 (normal range <0.9); results consistent with a EBV reactivation. Two weeks after the initial examination the eruption had almost abated altogether and four weeks later serologic testing revealed an EBV capsid antibody IgM EV of 2.8 (normal range 0-19.9), EBV capsid antibody IgG EV of >20 (normal range 0-19.9), EBV early antigen D EV of 2.8 (normal range 0-19.9), EBV nuclear antigen EV of 2.1 (normal range 0-19.9), and an parvovirus B-19 Index EV of <0.9 (normal range <0.9). Bacterial cultures and titers were negative at the time of examination and two weeks later.


Figure 2Figure 3

Discussion

The course of this case of ULE was typical. ULE may or may not be preceded by a viral prodrome and is marked by coalescing erythematous papules predominately on one side of the body. It occurs mostly in children with a mean age of 2 years of age but has been reported in adults. The largest series of cases of ULE of 48 children found a mean duration of 5 weeks. A more recent report describing a variant of ULE termed unilateral mediothoracic exanthem noted spontaneous remission was seen 2 and 3 weeks after rash onset in the child and the adult, respectively.

A viral cause of ULE has been postulated but inconsistently identified. The most virus most closely linked to ULE is parvovirus B-19 [2]. The histology of ULE has been noted to manifest consistently with a superficial perivascular infiltrate of lymphocytes that often forms a tight cuff around blood vessels and eccrine ducts and to manifest sometimes with miliarial spongiosis and exocytosis of lymphocytes into the acrosyringium [3, 4]. There does not have to be a rise in IgG or IgM levels during reactivation of EBV [5].

This case suggests that (1) EBV might be a cause ULE (2) Viral IgM might not necessarily elevated when a virus is the causal etiology of ULE (3) ULE may be linked to reactivation of a viral infection rather than acute viral infection and (4) ULE has a consistent clinical and histological presentation irrespective of causal virus.

The presence of IgG to EBV and detectable EBV virus which disappeared in short order while proof of viral reactivation is not itself EBV caused this unilateral eruption. The role of reactivation of viral infections (EBV but other herpes viruses as well) in skin eruptions and disease is an area that has gained increasing attention [8]. Whether the reactivation of virus found serologically in disease states is a causal phenomenon or an epiphenomenon is a controversial and complex matter. Quantities of EBV increase during times of stress that have been noted to include space flight, marathon training and antarctic exploration without evidence of disease. Thus the significance of increased levels of circulating EBV in otherwise healthy individuals is unclear. Increased and detectable viral replication when found while a disease state exists is suggestive that the EBV has a role in a disease not definitive proof. Complicating this calculation is that as will be discussed below, in certain pathologic states, multiple viruses can simultaneously increase their number while a disease state arises and progresses. Finally, the basis for a the clinical appearance of a particular eruption caused by EBV has yet to be defined.

Multiple techniques exist for assessing viral activity including the following: (1) polymerase chain reaction testing of blood fluid tissue for the presence of virons and viral DNA sequences; (2) immunohistological and immunofluorescent testing; and (3) viral cultures. The most means of testing that are positive, the more definite the role that reactivation can be ascribed to a pathologic state.

One well defined relationship of viral reactivation includes: the association of human herpes virus 6 infection with drug reaction with eosinophilia and systemic symptoms and anticonvulsant hypersensitivity syndrome [9]. This relationship has also been found with reactivation of cytomegalovirus (CMV) or EBV. Interestingly, when HHV-6 titers increase reactivation of HHV-7, CMV and/or EBV can also manifest following such drug eruptions [10]. In one study, the cascade of virus reactivation initiated by HHV-6 or EBV extended to EBV or HHV-7, and eventually to CMV [11].

Reactivation of Epstein-Barr virus has been linked to inflammatory diseases, diseases with inflammatory and neoplastic qualities, neoplasms, and immunosuppressive medications. The inflammatory diseases reactivation EBV has been lined to include the following: (1) ampicillin-induced cutaneous eruption associated with Epstein-Barr virus [12]; (2) florid reactions to mosquito bites [13]; (3) anticonvulsant hypersensitivity syndrome [14]; (4) Sjogren's syndrome [15, 16]; and (5) Gianotti-Crosti syndrome [17]. Although some reports link pityriasis lichenoides to EBV, I have not located any report linking it to reactivation of EBV. Diseases straddling inflammatory and neoplastic disease, such as reactive Epstein-Barr virus-related polyclonal lymphoproliferative disorder[18] and fatal hemophagocytic syndrome, have been linked to EBV reactivation [19]. The neoplastic diseases reactivation of EBV has been linked to include the following: Burkitt's lymphoma; Hodgkin's lymphoma; lymphomas and lymphoproliferative diseases in the immunocompromised; and nasopharyngeal and gastric carcinoma [20].

Reports linking immunosuppressive medications to diseases associated with reactivation of EBV include the following: (1) a patient who developed an EBV infection with the clinical features of an infectious mononucleosis, after immune suppression with cyclosporine and two courses of anti-thymocyte globulin for severe aplastic anemia [21]; (2) patients with lymphoma-related methotrexate use [22]; and (3) a patient taking prednisone preceding fatal fulminant hepatitis [23].


Conclusion

Much work still needs to done fitting the role of viruses into to human disease. This report suggests that EBV is related to ULE. Understanding the findings in this report will require other reports to explicate whether the relationship of ULE and EBV is causal or incidental. The basis for the unilateral appearance of this eruption is also in need of explication as it follows a pattern that no other eruption follows.

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