Herpes zoster of the nipple: rapid DNA-based diagnosis by the loop-mediated isothermal amplification method

INTRODUCTION

Herpes zoster is a distinctive syndrome caused by reactivation of varicella zoster virus (VZV) from the nerve cell bodies in the sensory ganglia. ¹ Usually, the clinical features of herpes zoster are characteristic, but the differentiation of herpes simplex and herpes zoster is not always possible on clinical grounds alone. We report a case of herpes zoster of the nipple clinically indistinguishable from mammary herpes simplex virus (HSV) infection. Rapid confirmation of the diagnosis based on viral DNA was made by a loop-mediated isothermal amplification (LAMP) method.

CASE REPORT

A 28-year-old Japanese man presented with painful lesions on his right nipple arising five days previously. He did not have any significant past medical history. On physical examination, there were grouped erosions and vesicles on an erythematous base affecting the right areola and the surrounding skin (Figure 1A and B). Some of the lesions were crusted. A lesional Tzanck smear from the vesicle revealed giant cells. An initial clinical diagnosis of mammary herpes simplex was considered but to explore the differential diagnosis, viral DNA was amplified by the loop-mediated isothermal amplification (LAMP) method. A swab sample from the nipple lesion was placed into 1 mL of sterilized water, and directly mixed with Loopamp^© DNA amplification kit (Eiken Chemical Co, Japan) and sets of primers for VZV, HSV-1 or HSV-2 LAMP as described elsewhere. ^2,3 Each mixture was incubated at 63°C for one hour. Then an LA-100 Turbidimeter (Teramecs, Kyoto, Japan) was used to measure turbidity. DNA replication was observed only in the VZV LAMP mixture, and this supported a diagnosis of herpes zoster. The patient was treated with 3000 mg of daily valacyclovir for seven days. After antiviral treatment, the lesion had healed and the pain had resolved completely. Cutaneous lesions caused by HSV and VZV represent common dermatoses. In most cases, a correct diagnosis can be made by the characteristic clinical features. However, in some cases, especially in patients with immunosuppression or with haematopoietic disorders, cutaneous herpes infections can present with atypical clinical presentations. ¹

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Figure 1

Clinical appearance. Grouped erosions and vesicles on an erythematous base affecting the right areola and the surrounding skin. Some of the lesions were crusted (A). Larger magnification (B)

Several tests can be used to confirm the clinical diagnosis of herpes virus infections. A Tzanck smear from herpetic lesions shows the characteristic findings such as acantholytic and multinucleated giant cells, but cannot distinguish between HSV and VZV disease. Viral cultures and immunofluorescence require substantial time and specialized equipment to obtain accurate results. Polymerase chain reaction has become a valuable tool to detect herpes virus infection; ⁴ but it is not yet available routinely in hospital laboratories.

LAMP is a novel nucleic acid amplification method, which amplifies DNA with high specificity, efficiency and speed, and has been used widely to detect various infectious agents. ⁵ The most significant advantage of LAMP is its ability to amplify specific DNA sequences under isothermal conditions within a short time. Herpetic skin lesion swab samples can be used for the LAMP assay without a DNA extraction procedure. ^2,3 In our case, by using the LAMP assay, VZV-DNA was detected from a skin swab specimen in an assay time of only one hour. In conclusion, rapid diagnosis of herpetic lesions by the LAMP method can be a convenient and useful way to confirm a specific herpes virus diagnosis and this helps the clinician decide on the most appropriate dosage of antiviral agents, especially in patients with atypical skin lesions.