Oral acyclovir prevents herpes simplex virus-associated erythema multiforme

A young woman suffering from recurrent erythema multiforme associated with relapsing gluteal herpes simplex is presented, in whom long-term treatment with oral acyclovir prevented herpes episodes as well as erythema multiforme.     

Oral acyclovir for the prevention of herpes-associated erythema multiforme

Herpes simplex virus is the single most common precipitator of erythema multiforme. Typically, erythema multiforme lesions appear 10 to 14 days after a recurrent herpes simplex virus infection and attacks can be disabling when they occur at frequent intervals. Prior to the introduction of acyclovir (Zovirax), there was no effective therapy to prevent herpes-associated erythema multiforme. Four patients were treated with a maintenance dose of acyclovir for periods ranging from 10 to 26 months; there were no significant side effects from the drug and only one recurrence of erythema multiforme. Oral acyclovir may become the treatment of choice for herpes-associated erythema multiforme.     

Erythema multiforme following polymorphic light eruption: a report of two cases

We report two patients in whom episodes of polymorphic light eruption were followed by recurrent erythema multiforme on exposed and nonexposed sites. Treating the polymorphic light eruption with prophylactic PUVA and/or oral prednisolone or cyclosporin prevented the development of erythema multiforme, suggesting that the two events are related. It is possible that erythema multiforme develops as a response to the same causative antigen as polymorphic light eruption.     

阿达木单抗联合丙种球蛋白治疗HSV相关性慢性复发性多形红斑一例

本文报道种球蛋白联合阿达木单抗治疗单纯疱疹病毒(HSV)相关的复发性多形红斑1例并复习相关文献。患儿,男,9岁。口唇反复糜烂、渗出15个月,全身反复红斑8个月。皮肤科查体:口唇糜烂,背部、四肢散在暗红色斑片,局部周边可见松弛水疱。病理检查符合多形红斑,单纯疱疹病毒I型IgG滴度444.72 RU/mL。诊断为单纯疱疹病毒感染相关多形红斑,给予伐昔洛韦抗病毒治疗的同时,给予阿达木单抗联合人免疫球蛋白治疗,2周后皮损消退,单纯疱疹病毒I型IgG滴度明显下降。     

Recurrent erythema multiforme: tissue typing in a large series of patients

Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8, and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.     

Identification of herpes simplex virus DNA in lesions of erythema multiforme by the polymerase chain reaction.

An association between erythema multiforme and herpes simplex virus infection has been supported by clinical studies and by the detection by immunofluorescence of herpes viral antigen in sera and skin biopsy specimens of patients with erythema multiforme. In rare cases, the virus has also been isolated in cultures of skin biopsy specimens of erythema multiforme. To investigate further the association between erythema multiforme and herpes simplex virus, we used the polymerase chain reaction for herpes simplex virus to examine skin lesions from patients with erythema multiforme. In this study herpes simplex virus DNA was detected in 11 of 31 biopsy specimens of erythema multiforme; six additional cases showed equivocal amplification results, which is suggestive of low amounts of viral DNA. Seven skin and mucosal biopsy specimens with the histologic changes of herpes virus infection served as positive controls: all were positive for herpes simplex virus DNA. Viral DNA was not detected in control biopsy specimens from skin excised for unrelated conditions. These studies support the association of herpes simplex virus in the pathogenesis of some cases of erythema multiforme. The polymerase chain reaction provides a quick and effective method of detecting herpes simplex virus in lesions of herpes-associated erythema multiforme. Furthermore, the polymerase chain reaction may delineate those cases of erythema multiforme that are etiologically related to herpes virus infection and therefore might be treated with acyclovir to prevent recurrence.     

Recurrent erythema multiforme: clinical features and treatment in a large series of patients

Recurrent erythema multiforme is an uncommon disorder. We have reviewed the clinical features and treatment of 65 patients with this condition. The mean number of attacks per year was six (range 2–24). and the mean duration of the disease was 9.5 years (range 2–36) reflecting its chronicity. The majority of patients had oral mucous membrane involvement (69%). In 46 patients (71%) the condition was precipitated by a preceding herpes simplex virus infection. Acyclovir was found to be the most useful first-line treatment, with 55% of patients deriving benefit from either continuous oral acyclovir or a patient-initiated 5-day oral course at the onset of herpes simplex virus infection. Of those failing to respond to acyclovir, a small proportion responded to dapsone. The most resistant patients (11) were treated with azathioprine. with complete disease suppression in all cases.     

Erythema multiforme

In summary, the diagnosis of erythema multiforme is appropriate for a self-limiting or episodic cutaneous or mucocutaneous illness with skin lesions morphologically and histologically compatible. With typical erythema multiforme minor, characterized by classic skin lesions with or without oral erosions, most patients' disease is associated with recurrent herpes simplex infections. This is particularly true with recurrent erythema multiforme. Symptomatic conservative care, antibiotic treatment for purulent secondarily infected oral lesions, and avoidance of systemic steroids are appropriate therapeutic guidelines. The more serious syndrome, erythema multiforme major, or Stevens-Johnson syndrome, is characterized by skin lesions that are somewhat atypical and different from those of erythema multiforme minor in association with erosions on multiple mucosal surfaces. Drugs and mycoplasmal infections are important precipitating factors for erythema multiforme major. Hospitalization and laboratory tests are often required because of the severity of the illness and the occasional damage to other organ systems. Conservative, symptomatic care, withdrawal of any drug that may have caused the illness, treatment of any mycoplasmal infection, and antibiotic therapy for purulent secondarily infected lesions are worthwhile therapeutic measures. Early treatment with systemic steroids may be helpful in preventing further damage, and the risks and potential benefits of such therapy must be evaluated on an individual basis.     

A Case of Herpes-associated Erythema Multiforme in a Japanese Child

A case of a five-year-old Japanese boy with herpes-associated erythema multiforme (HAEM) was reported. The patient had eleven recurrences of herpes labiaris within one year; four of these recurrences were accompanied by erythema multiforme. A study of the human leukocyte antigens revealed the presence of HLA-DQW3, which has been reported to be significantly frequent in Caucasian patients with HAEM. Oral administration of acyclovir at the onset of herpes labialis was effective in preventing HAEM. Early administration of oral steroids at the onset of HAEM also prevented its exacerbation.     

Light-induced postherpetic erythema exsudativum multiforme

A 37-year-old man had erythema multiforme over a period of 20 years following recurrent herpes simplex infections. On the basis of the results of provocative UV-A tests as well as histological findings a diagnosis of photosensitive erythema multiforme was made. The erythema multiforme exsudativum like variant of polymorphous light eruption is discussed in the differential diagnosis.     

Topical treatment of recurrent herpes simplex and post-herpetic erythema multiforme with low concentrations of zinc sulphate solution

The preventive effect of low concentrations of zinc sulphate solution in recurrent herpes simplex of the skin and oral mucous membrane is reported. Treatment with zinc sulphate solution of the skin at the site of the herpetic infection also prevents relapse of post-herpetic erythema multiforme. For the skin, 0.025-0.05%, and for the oral mucous membrane, 0.01-0.025% zinc sulphate solution was used.     

Treatment of mucocutaneous presentations of herpes simplex virus infections

Infections by herpes simplex virus (HSV) types I and II are diverse and quite frequent. After primary infection, the virus establishes a life-long latency in the sensory ganglia and recrudescences may occur at an unpredictable rate. Recurrent labial and genital herpes infections represent the majority of clinical manifestations of HSV infections. Their management is currently well established using evidence-based medicine data. Primary labial herpes is generally not treated with antivirals in otherwise healthy children, although intravenous aciclovir may be offered in severe primary infections, particularly in the immunocompromised patient. The decision whether or not to treat recurrent labial herpes should be evaluated individually and depends on the frequency and severity of relapses, the impairment of the quality of life, and the cost of therapy. Patients with mild disease may benefit from topical therapy, and those with severe and frequent recurrences may be considered for intermittent or long-term oral antiviral therapy. Primary genital herpes is treated with oral or intravenous antivirals, depending on the severity of the infection and associated symptoms. Recurrent genital herpes can be managed with episodic short courses of oral antivirals in patients whose recurrences are moderate to severe and rare, and have a clear prodrome. Patients with >5 episodes/year, severe recurrences or unrecognisable prodromes may be best managed with long-term suppressive antiviral prophylaxis. HSV is also responsible for a variety of other clinical manifestations, including herpetic whitlow, neonatal infection, disseminated and atypical cutaneous infections, traumatic herpes, eczema herpeticum, and HSV-associated erythema multiforme. HSV infection may also represent a complication following cosmetic procedures of the oro-facial region, surgical and dental interventions, sun exposure and burns. Precise treatment guidelines for these HSV infections are not firmly established.     

Successful differentiation of herpes zoster‐associated erythema multiforme from generalized extension of herpes by rapid polymerase chain reaction analysis

The polymerase chain reaction (PCR) assay for varicella zoster virus (VZV), herpes simplex virus (HSV)‐1 and HSV‐2 is available for use. Sometimes the differential diagnosis of the generalized herpes zoster (HZ), HSV1/2, and drug eruption is difficult. We report a case of HZ followed by the vesicular erythema multiforme (EM)‐like lesion. In this case the use of PCR was of great assistance. A 78‐year‐old Japanese man without any significant previous history of disease was admitted to our hospital complaining of zosteriform vesicle on an erythematous base from his right shoulder to the upper arm. We diagnosed him with HZ at the level of right Th2. In spite of the prompt start of antiviral therapy, a secondary new vesiculous erythema developed on his trunk. Clinically, it was quite difficult to differentiate the lesion from the generalized HZ. Rapid PCR assay of effusion and crust for VZV was performed. A PCR assay of VZV was positive for the crust taken from the primary lesion, while it was negative for the effusion and crust of the secondary widespread lesion. We diagnosed the secondary widespread lesion as an EM‐type drug eruption induced by acyclovir, or an EM associated with herpes zoster. We then stopped the use of acyclovir and applied steroid ointment of a very strong class for the secondary lesions, which improved after a few days. A PCR assay for VZV was useful for ruling out the generalized HZ in our case with secondary developed vesiculous lesions.     

A double-blind, placebo-controlled trial of continuous acyclovir therapy in recurrent erythema multiforme

Twenty patients who suffered from more than four attacks of erythema multiforme (EM) per year were enrolled in a 6-month double-blind, placebo-controlled trial of acyclovir 400 mg twice daily. Fifteen patients had disease precipitated by recurrent herpes simplex. In the acyclovir-treated group the median number of EM attacks during the treatment period was zero, compared with three in the placebo-treated group (P < 0.0005, Wilcoxon rank sum test). Seven of the 11 patients treated with continuous acyclovir did not have any attacks of EM while taking the drug, and one showed almost complete disease suppression. Following treatment with acyclovir, two patients went into complete remission, whereas all individuals in the placebo group continued to have attacks. In the acyclovir-treated group nine of the 11 patients had herpes simplex-precipitated disease. One of the two patients with idiopathic disease showed complete disease suppression while on acyclovir, lending support to the view that idiopathic recurrent EM may be related to subclinical herpetic infection. In this study, we have shown that continuous acyclovir therapy can completely suppress attacks of recurrent EM and, in some cases, may induce disease remission.     

HLA typing of patients with herpes simplex recidivans and postherpetic erythema exsudativum multiforme

62 patients suffering from recurrent herpes simplex, with ten out of them showing postherpetic erythema multiforme, have been investigated with special reference to histocompatibility standardisation. In comparison with a control group (n = 170), our patients revealed a high and statistically significant level of HLA-B5 (p less than 0,01). Postherpetic erythema multiforme seems to be associated with HLA-A9.     

Recurrent herpes labialis during isotretinoin therapy: is there a role for photosensitivity?

Isotretinoin (13-cis-retinoic acid) is one of the synthetic retinoids derived from vitamin A. Vitamin A derivatives demonstrate virucidal activity, both in vivo and in vitro. Isotretinoin has been used for the treatment of recurrent herpes simplex with encouraging results. However, we present a case with frequent attacks of herpes labialis during isotretinoin therapy for acne, who had a marked decrease in frequency of recurrences following strict use of sunscreens.     

Herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs

Herpes simplex virus (HSV) infections often manifest as acute self-limiting eruptions of grouped vesicles, which have a tendency to recur. Common manifestations include that of gingivostomatitis, vulvovaginitis, recurrent erythema multiforme, herpetic whitlow, and eczema herpeticum. We report a case of HSV-1 presenting as a symmetrical intracorneal blistering eruption involving the lower limbs in a patient with no previous history of herpes simplex infection.     

Detection of herpes simplex virus DNA in serum and oral secretions during acute recurrent herpes labialis

Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which the virus may be present in the blood during a localized infection in otherwise healthy patients is still unknown. Literature on patterns of HSV shedding into the oral cavity at the prodromal stage of the disease, during recurrences, and also during asymptomatic periods is still lacking. The present study aims at the detection of HSV DNA in the serum and oral secretions during acute herpes labialis using a highly sensitive technique, the polymerase chain reaction (PCR). The study included 10 patients with acute herpes labialis and five healthy controls. Using PCR, herpes simplex virus DNA was detected in the serum of seven patients (70%) and in the saliva of nine patients (90%). One of the control cases showed positive HSV DNA in the saliva (20%). There was good statistical agreement between the presence of HSV DNA in the serum and saliva. Frequency of attacks, patient's age, and gender had no statistically significant effect on the presence of the virus in serum or in saliva. It is concluded that HSV viremia during attacks of recurrent herpes simplex is more frequent than previously appreciated.     

High frequency of detection of herpes simplex virus DNA in the oral cavity of patients with eczema herpeticum

BACKGROUND: It has been reported that herpes simplex virus (HSV) DNA was detected in the oral cavity of patients with herpes labialis under various conditions such as during oral surgery. OBJECTIVE: The frequency of detection of oral HSV DNA was compared between first or recurrent episodes of eczema herpeticum and recurrent type herpes labialis. PATIENTS AND METHODS: Oral swabs were collected from 7 patients with eczema herpeticum and 9 with herpes labialis. The detection of oral HSV DNA was performed by the polymerase chain reaction method. RESULTS: Oral HSV DNA was detected in 6 out of 7 patients (86%) with eczema herpeticum and 3 of 9 (33%) with herpes labialis. CONCLUSIONS: The high frequency of oral HSV DNA detection in eczema herpeticum suggests that subclinical herpetic lesions may develop in the oral cavity of patients with a first episode of eczema herpeticum or may occur during asymptomatic oral HSV shedding in people with recurrent eczema herpeticum.