Zoster duplex: a clinical report and etiologic analysis

Abstract

Objective: Herpes zoster (HZ) duplex is a rare disease presentation. The mechanisms of varicella zoster virus (VZV) reactivation in multiple dermal regions are unknown. To present a HZ duplex case occurring in an immunocompetent woman and to analyze the possible underlying causes of HZ duplex. Methods: We present a HZ duplex case in an immunocompetent woman and analyzed the possible contributing factors in 36 HZ duplex cases. Continuously distributed variables were categorized by numbers and percentages. Results: In our study, 24 cases (66.7%) were from Asia, 16 cases (44.4%) were in individuals ≥ 50 years of age, and 17 cases (47.2%) occurred in immunocompromised patients. Of the 36 cases, 23 involved women (63.9%) and 13 involved men. Eighteen patients suffering from HZ duplex, 13 of which were women (72.2%), did not suffer from any chronic systemic disease or have a long history of taking drugs. Conclusion: HZ duplex is a rare event that can occur in both immunocompetent and immunosuppressed individuals. HZ duplex might be associated with the Asia region, advanced age, immunosuppression, and being female.

Introduction

Herpes zoster (HZ) is a relatively common disease in regions of the world where the detection rate of serum varicella zoster virus (VZV) IgG in healthy individuals is 40-100% [1]. One million new episodes of HZ are estimated to occur yearly in the United States [2]. Following varicella infection, VZV typically remains latent in the dorsal root ganglia of patients, as demonstrated by autopsy studies [3]. After reactivation, viral replication produces typical unilateral HZ lesions, usually restricted to one-half of the body [4]. However, sometimes the virus affects more than one dermatome, a condition referred to as multidermatomal HZ. HZ occurring in two, noncontiguous, widely separated dermatomes, referred to as HZ duplex unilateralis or bilateralis [5], is very rare, with an incidence of less than 0.1% of all HZ cases [6]. The mechanism of VZV reactivation in multiple dermal regions is unknown. In the past, HZ duplex was reportedly most common in immunocompromised patients, but HZ duplex also occurs in immunocompetent hosts. We present a case of HZ duplex bilateralis in an immunocompetent patient that occurred on both sides of abdomen and back with a relatively symmetrical distribution. Moreover, we analyzed literature pertaining to 36 HZ duplex cases to clarify their underlying cause.

Case report

A 49-year-old woman presented with a 5-d history of pain on the left side of her chest and abdomen. After onset of the pain, grouped, vesicular eruptions developed along the left side of her chest and abdomen. Three days after the onset of pain, the same symptoms developed along the right side of the chest and abdomen. She had no personal or family history of HZ, she had not received the Zostavax vaccine, and did not recall having chicken pox. She was afebrile, as the severe pain led to poor sleep and dietary habits. Previously, the patient was healthy, did not display similar rashes, erythema, or blisters on the trunk, and she had not suffer from any chronic systemic diseases in recent years and was not taking any medication. Before HZ duplex, psycho-social stress and overnight working did not exist. The patient had no headache and no other systemic complaints. Cutaneous examination revealed bilateral multiple grouped vesicles and erosions over an erythematous base on the anterior side, corresponding to the left T10 and right T9 dermatomes (Figure 1). Systemic examination did not reveal any abnormality. The following laboratory tests were all normal: blood cells, liver function, renal function, blood sugar, blood lipids, complement (C3, C4), immunoglobulin, syphilis, HIV, chest radiograph, and ultrasonography of the liver, kidneys, spleen, pancreas, and gallbladder. Skin biopsy of an early vesicular lesion revealed intracellular and intercellular edema, as well as ballooning degeneration in the epidermis and lymphocytes and other inflammatory cell infiltration in the superficial dermis, Figure 2A-left sidedness, Figure 2B-right sidedness (Figure 2). Electron microscopy showed multiple annular VZV particles in the superior part of the epidermis, Figure 3A-left sidedness, Figure 3B-right sidedness (Figure 3). This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Harbin Medical University. Written informed consent was obtained from this participant.

Figure 1.

Cutaneous examination revealed bilateral multiple grouped vesicles and erosions over an erythematous base on the anterior side, corresponding to the left T10 and right T9 dermatomes.

Figure 2.

Skin biopsy of an early vesicular lesion revealed intracellular and intercellular edema, as well as ballooning degeneration in the epidermis and lymphocytes and other inflammatory cell infiltration in the superficial dermis (A-left sidedness, B-right sidedness. HE stain, original magnification × 400).

Figure 3.

Electron microscopy showed multiple annular VZV particles in the superior part of the epidermis (A-left sidedness, B-right sidedness).

Treatment was as follows: oral famciclovir, vitamin B, E, topical Lightyellow Sophora Root herpes tincture, and infusion of foscarnet sodium injection. Significant improvement was observed after 1 week and the lesions resolved completely within 2 weeks. However, at a follow-up visit 1 month later, the patient reported persistent pain, for which she took orally gabapentin capsules.

Discussion

We reported a case of HZ duplex in an immunocompetent female patient. Nearly symmetrical rashes are very rare, with only 36 cases (including this case) of HZ duplex unilateralis or bilateralis having been reported to date. The age, sex, involved dermatomes, ethnicities, medications taken, and underlying illnesses are summarized in Table 1 [7-40,43,44]. We analyzed the possible underlying causes of HZ duplex.

Table 1.

Basic conditions of 36 patients

Num/Ref	Age/Sex	Dermatomes	Drug	Underlying disease	Regions
1/[7]	30/M	L: T10; R: T10		HIV	Indian
2/[8]	24/F	L: Eye; R: Tigh	-	-	Indian
3/[9]	10/M	L: L2-4; R: C4-6		HIV; Haemophilia	Indian
4/[9]	50/M	L: C3-5; L: T7-9	Immunosuppressive drugs	Renal transplant	Indian
5/[10]	50/F	L: T3, 4; R: T3, 4	-	-	Indian
6/[11]	45/M	L: Maxillary; R: T9	-	-	Indian
7/[12]	67/F	L: T7, 8; R: L4, 5		Hypertension; Osteoporosis	Korean
8/[13]	49/F	L: T4; R: T4	5-fuorouracil methotrexate adriamycin	Breast cancer	Korean
9/[14]	5/F	L: T2; R: T5	-	-	Korean
10/[15]	22/F	L: S3; R: T7	Chemotherapy	Leukemia	Korean
11/[16]	47/F	L: L3, 4; R: T7	-	-	Korean
12/[17]	50/F	L: T2; L: T8	-	Breast cancer (9 years ago, no metastasis)	Korean
13/[18]	21/M	L: T10; R: T9, 10	Prednisone	Ulcerative colitis	Korean
33/[36]	4/F	L: T5; R: T7-8	-	-	Korean
14/[19]	52/F	L: T8; R:T2, 3	Glucocorticoid	Systemic lupus	Chinese
15/[20]	52/F	L: T6-8; R: T6-10	-	-	Chinese
16/This paper	49/F	L: T10; R: T9	-	-	Chinese
17/[21]	80/F	L: C3; R: L3, 4	-	-	Taiwan
18/[22]	72/F	L: Facial paresis		Diabetes	Japanese
		R: Peroneal paresis
19/[23]	3/F	L: T2-4; R: T2-4	Chemotherapy	Lymphocytic leukemia	Japanese
20/[24]	77/M	L: S3, 4; R: T6-8	?	Gastric cancer	Japanese
21/[6]	61/M	L: T2, 3; R: C5	-	-	Japanese
22/[25]	64/F	L: T8; R: L4	Prednisone	Polymyositis; Diabetes	Arabic
23/[26]	24/M	L: T8; R: T8	-	-	Pakistanian
24/[27]	67/M	L: V1, 2; R: V3	Oral steroids	-	Caucasian
25/[28]	16/F	L: T4-7; R: V2	-	-	Caucasian
26/[29]	69/M	R: T5-7, 10, 12, L3-4	Cyclosporine prednisone mycophenolate	Renal allograft	American
		L: T4-6, 12, L3-5
27/[30]	51/F	L: S1; R: T!0	-	-	American
28/[31]	10/M	L: T2; R: V, T4	Steroids, chemotherapy	Non-Hodgkin’s lymphoma	American
29/[32]	37/F	L: T11; R: T3	Oral steroids	Asthma	American
32/[35]	14/M	L: L1; R: V1	-	-	American
30/[33]	73/F	L: T9, 10; R: L2, 3, S3	-	-	Germany
31/[34]	70/F	L: L1, 2; R: C4, T2	Chlorambucil, methylprednisolone	Chronic lymphocytic leukemia	Belgium
34/[37]	10/M	L: V1; R: C7-8	-	-	South African
35/[38]	6/F	R: T10-12	-	-	Egyptian
36/[39]	11/F	R: T11-12, L3–5	-	-	Egyptian

Explanation: ‘-’ means ‘did not medication’ in the fourth column. ‘ref’=reference.

HZ duplex was observed in all ethnic groups. In our study, 24 cases (66.7%) were from Asia. Almuneef et al., (2004) reported that Asian individuals are more susceptible to VZV, while East Asians are more susceptible to other viruses including Epstein-Barr virus and hepatitis B [41]. The VZV-IgG detection rate was lower in the sera of healthy Asian individuals than of those residing in other regions [1]. The highest number of HZ duplex patients was observed in Asia, suggesting a genetic susceptibility for developing HZ duplex.

HZ predominantly affects the elderly. HZ increases with age and as VZV-specific T cell-mediated immunity declines, VZV-specific memory of CD4 T cells decreases [2]. Seroprevalence of VZV-IgG increased with age [1,45]. Approximately 50% of HZ cases occur in individuals aged 50 years or older in the United States each year [42]. In our study, the mean age of the patients was 40.1 years (age range 3-80 years) and 16 cases (44.4%) were in individuals ≥ 50 years of age. HZ duplex incidence increased with age.

Multiple dermatome involvement and bilateral asymmetrical distribution of HZ have been reported in the past, with the majority of the cases being in immunosuppressed adults and children. In our study, 17 HZ duplex cases (47.2%) occurred in immunocompromised patients, including those affected by HIV, cancer, and other diseases, or those taking longterm medications including immunosuppressive agents, chemotherapeutic agents, and corticosteroids. HZ is caused by the reactivation of a neurotropic virus, VZV, lying in a dormant state in sensory dorsal root ganglia. Decreased immunity may be the cause of viral reactivation.

Reflecting the susceptibility of woman to HZ duplex, 23 women (63.9%) and 13 men were included in our study. Eighteen HZ duplex patients, 13 of which were women (72.2%), did not suffer from any chronic systemic disease or have a long history of taking drugs. Women are more likely to spend time with children than are men, and children are susceptible to varicella [43]. A higher seroprevalence of VZV was observed in women than in men [42]. These data are an extension of observations reported in several studies showing women have higher incidence of HZ [46,47]. A study by Hernandez et al., suggested that a genetic predisposition to HZ is more frequently inherited along maternal lines. Perhaps being female is an independent risk factor for rare presentations of HZ duplex.

Conclusion

HZ duplex is a rare event that can occur in both immunocompetent and immunosuppressed individuals. HZ duplex might be associated with the Asia region, advanced age, immunosuppression, and being female.

Disclosure of conflict of interest

None.