Herpes simplex virus and cytomegalovirus co‐infection presenting as exuberant genital ulcer in a woman infected with human immunodeficiency virus

In patients infected with human immunodeficiency virus (HIV), genital herpes can result in severe and atypical clinical presentations, and can become resistant to aciclovir treatment. Rarely, these manifestations may represent concurrent herpes simplex virus (HSV) with other agents. We report a 41‐year‐old black woman with HIV who presented with extensive and painful ulceration of the genitalia. Histological examination of a biopsy sample was suggestive of herpetic infection, and intravenous aciclovir was started, but produced only partial improvement. PCR was performed on the biopsy sample, and both HSV and cytomegalovirus (CMV) DNA was detected. Oral valganciclovir was started with therapeutic success. CMV infection is common in patients infected with HIV, but its presence in mucocutaneous lesions is rarely reported. This case exemplifies the difficulties of diagnosis of genital ulcers in patients infected with HIV. The presence of exuberant and persistent HSV genital ulcers in patients with HIV should also raise suspicions of the presence of co‐infection with other organisms such as CMV.     

The role of human herpesvirus-6, Epstein–Barr virus and cytomegalovirus infections in the etiopathogenesis of different types of cutaneous drug reactions

Background Recently, it has been recognized that drug‐induced hypersensitivity syndrome (DIHS) is associated with reactivation of human herpesvirus‐6 (HHV‐6), Epstein–Barr virus (EBV) and cytomegalovirus (CMV). However, whether those viruses have a role in the development of cutaneous drug reactions (CDRs) other than DIHS is not known. Objective To investigate the role of HHV‐6, EBV and CMV infections in the etiopathogenesis of different types of CDRs. Methods Eighteen patients with diagnosis of CDR according to the clinical and histopathological findings were evaluated. Real‐time polymerase chain reaction (PCR) was used for the detection of EBV, CMV, and HHV‐6 DNA in lesional skin biopsy specimens; EBV and CMV DNA in serum samples; and HHV‐6 DNA in peripheral blood mononuclear cells. Results The genome of HHV‐6 was detected only in the lesional skin of two patients with DIHS. Epstein–Barr virus and CMV DNA in the skin lesions, EBV and CMV genomes in the serum samples, and HHV‐6 DNA in the peripheral blood mononuclear cells were negative in all patients. Limitations The patient population was small and did not include all types of CDRs. Also, we had only two patients with DIHS. We had not been able to measure the increase in anti‐viral IgG titers in serial serum samples. Conclusion Epstein–Barr virus and CMV infections do not seem to have a role in the etiopathogenesis of CDRs including DIHS. The association between HHV‐6 infection and CDRs is likely to be limited to DIHS.     

Drug‐induced hypersensitivity syndrome due to carbapenem antibiotics

Drug‐induced hypersensitivity syndrome (DIHS) is characterized by a serious adverse systemic reaction that usually appears after a 3–6‐week exposure to certain drugs, for example, anticonvulsants. Many different precipitating factors have been reported, but the pathophysiology of DIHS remains unknown. However, reactivation of members of the human herpesvirus (HHV) family, and of HHV‐6 in particular, has been reported in patients with DIHS. We report the case of a 64‐year‐old man who developed a generalized erythematous rash, fever, hepatic failure, lymphadenopathy and an increased number of atypical lymphocytes. In addition, reactivation of HHV‐6 and cytomegalovirus (CMV) was demonstrated by real‐time quantitative amplification by polymerase chain reaction. The patient was given a diagnosis of DIHS due to carbapenem antibiotics based on his clinical course, laboratory data, and results of lymphocyte‐stimulation tests with various drugs. This is the first report, to our knowledge, of DIHS induced by carbapenem antibiotics.     

Clinical course of drug‐induced hypersensitivity syndrome treated without systemic corticosteroids

Background /aim Drug‐induced hypersensitivity syndrome (DIHS) is a severe reaction to drugs which characteristically occurs after a long latency period. In addition, human herpes virus 6 (HHV‐6) reactivation is a characteristic finding in DIHS, which has been known to be related to disease severity. Because DIHS has generally been treated by systemic corticosteroids, the natural clinical course is not clear. Methods Data for patients with both DIHS and HHV‐6 reactivation were retrospectively collected from four hospitals. Results Data were collected on 12 patients ranging in age from 21 to 76 years (median, 65.5). All cases had been suspected of DIHS at their initial visit, and the elevation of serum anti‐HHV‐6 antibody had been confirmed (4–256 times: median; 32). The culprit drugs were carbamazepine (6), salazosulfapyridine (4), mexiletine (1) and zonisamide (1). The period of latency from the first administration of the drug ranged from 15 to 50 days (median, 30). All patients were treated conservatively for DIHS without systemic corticosteroids. The peaks of the patients’ symptoms and laboratory findings were as follows (days from the onset of skin lesions): fever, 4–16 (median, 10.5); liver abnormality, 3–22 (median, 7.5); leukocytosis, 7–20 (median, 9). All patients recovered without pneumonia, myocarditis, nephritis or other systemic disease, from 7 to 37 days (median, 18) after withdrawal of the drug and from 11 to 44 days (median, 21) after the onset of skin lesions. Conclusion It might be unnecessary to give systemic corticosteroids immediately to all patients suspected of having DIHS.     

Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)-6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV). OBJECTIVES: To determine whether reactivation of HHV-6, HHV-7, CMV and/or EBV occurs in patients with DIHS. METHODS: Titres of IgG and IgM antibodies to HHV-6 and HHV-7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and HHV-7 were elevated simultaneously 21-38 days after the onset. RESULTS: IgG antibody titres to CMV and EBV were elevated 10-21 days after the elevation of HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV-6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. CONCLUSION: The present study suggests that in addition to HHV-6 reactivation, reactivation of HHV-7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.     

Several herpesviruses can reactivate in a severe drug-induced multiorgan reaction in the same sequential order as in graft-versus-host disease

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is a severe multiorgan systemic reaction. Numerous studies have linked reactivation of human herpesvirus (HHV)-6 with the development of DIHS. Recent articles have suggested that reactivation of other herpesviruses besides HHV-6 might also be involved in the development of DIHS. On the other hand, recent studies have provided evidence for a role of reactivation of various herpesviruses in the development of graft-versus-host disease (GVHD). OBJECTIVES: We attempted to determine whether sequential herpesvirus reactivation could be detected in four patients with severe DIHS, as observed in patients with GVHD, and be coincident with various clinical manifestations that developed after discontinuation of the causative drugs. METHODS: Detection and quantification of viral DNA [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HHV-6 and HHV-7] in sequential blood samples were performed using real-time polymerase chain reaction assays, based on TaqMan technology. RESULTS: In these patients, the cascade of virus reactivation initiated by HHV-6 or EBV extended to EBV or HHV-7, and eventually to CMV. Clinical manifestations of this syndrome followed by failure of various organs occurring despite discontinuation of the drug were coincident with these herpesvirus reactivations. CONCLUSIONS: These results suggest that various herpesviruses can reactivate in the setting of severe drug reactions in a similar sequential order to that described in GVHD. The sequential reactivation of these herpesviruses is responsible for the development of multiorgan failure occurring after discontinuation of the causative drug.     

A case of drug-induced hypersensitivity syndrome showing transient immunosuppression before viral reactivation during treatment for pemphigus foliaceus

Drug-induced hypersensitivity syndrome (DIHS) is one of the most severe drug adverse reactions, with characteristic biphasic symptoms. Reactivation of human herpesvirus-6 (HHV-6) is frequently observed, although the cause of DIHS is still unknown. A patient developed DIHS during treatment with diaminodiphenylsulphone for pemphigus foliaceus. The number of lymphocytes in his peripheral blood, and titres of serum total IgG and IgM and anti-desmoglein1 antibody transiently decreased just before reactivation of HHV-6, cytomegalovirus and Epstein-Barr virus. This observation suggests that transient suppression of both cellular and humoral immunity may trigger viral reactivation, which leads to the development of the second phase of DIHS.     

Stevens–Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug‐induced hypersensitivity syndrome,despite differences in cutaneous presentations

Background. Drug‐induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. Methods. Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant‐related DIHS (n = 6). Results. Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV‐6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. Conclusions. TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS.     

New aspects of drug-induced hypersensitivity syndrome

Drug-induced hypersensitivity syndrome (DIHS) is caused by a limited number of specific drugs and is characterized by late onset, infectious mononucleosis-like symptoms, and herpesvirus 6 (HHV-6) reactivation. Recently, the involvement of herpes viruses other than HHV-6, such as Epstein-Barr virus and cytomegalovirus, has been reported. Many approaches have been used to analyze the pathological mechanism, and have revealed new aspects of DIHS. Here, we focused on three key recent findings regarding DIHS: (i) overlap between DIHS and Stevens-Johnson syndrome/toxic epidermal necrolysis; (ii) the relevance of Epstein-Barr virus in the development of infectious mononucleosis-like symptoms of DIHS; and (iii) roles of monomyeloid precursors increased in the blood and plasmacytoid dendritic cells increased in the lesion skin in HHV-6 reactivation.     

Drug-induced hypersensitivity syndrome associated with human herpesvirus 6 and cytomegalovirus reactivation

We describe a patient with drug-induced hypersensitivity syndrome (DIHS) associated with human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) infection induced by sulfasalazine. Two weeks after starting sulfasalazine to treat a rectal ulcer, the patient developed disseminated macular erythema accompanied by fever, liver injury, and lymphadenopathy. Seroconversion of antibodies to HHV-6 was observed. Systemic steroid treatment was not effective against the eruptions. Five months after the onset, he presented with an acute febrile disease. The detection of CMV antigen on peripheral blood leukocytes and positive staining for CMV on cutaneous endothelium indicated active CMV infection. Furthermore, he developed a bacteremia of methicillin resistant Staphylococcus aureus. An association the CMV reactivation with DIHS was suggested, although there remains the possibility that the systemic steroid treatment precipitated CMV reactivation. Recently, HHV-6 has been documented to have immunomodulating effects and to be associated with CMV reactivation. Therefore, we should pay attention to the possibility of CMV reactivation in patients with DIHS in whom the immunomodulating virus of HHV-6 has been reactivated.     

Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs

Drug‐induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi‐organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus‐6 (HHV‐6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation‐regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV‐6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG‐associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.     

药物超敏反应综合征发病机制及治疗的研究进展

药物超敏反应综合征是一种具有特异征候的重症药疹。目前认为,在一定的遗传背景下,机体对药物活性代谢产物解毒功能的缺陷是其病因之一,人疱疹病毒-6感染再激活也参与了此病的发生。药物及病毒再激活引发的免疫过敏反应所致组织损害主要南CD8 细胞毒性T淋巴细胞造成。针对其病理生理改变,最有效的治疗是采用激素与免疫球蛋白联合疗法。     

Identifying potential pitfalls in conventional herpes simplex virus management

In recent years, it has become increasingly clear that genital ulcers from herpes simplex virus (HSV) are associated with HIV acquisition. In light of this evolving synergy in transmission and the availability of effective antiviral therapy, proper diagnosis and management of HSV becomes increasingly important. Unfortunately, conventional HSV management is founded on several popular misconceptions. Herein, we hope to dispel these common misconceptions and expand the current model of herpetic reactivation. By doing so, we aimed to unveil potential pitfalls in current herpetic management.     

Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash and internal organ involvement. In the vast majority of patients in Japan, the causative drugs for DIHS are limited to the following eight: carbamazepine, phenytoin, phenobarbital, zonisamide, mexiletine, dapsone, salazosulfapyridine and allopurinol. The association of human herpesvirus (HHV)-6 reactivation with DIHS has been reported by various groups. OBJECTIVES: To confirm the relationship between the flaring and severity of DIHS and HHV-6 reactivation. METHODS: We evaluated 100 patients with drug rash and systemic symptom(s) caused by the drugs associated with DIHS. HHV-6 reactivation was examined by serological antibody assay and quantitative real-time polymerase chain reaction assay of serial serum samples. RESULTS: Anti-HHV-6 IgG titres increased in 62 of 100 patients, 14-28 days after the onset of symptoms. These patients suffered from severe organ involvement and a prolonged course compared with 38 patients showing no reactivation of HHV-6. Significant amounts of HHV-6 DNA were detected in serum samples from 18 of the 62 patients. Flaring of symptoms such as fever and hepatitis was closely related to HHV-6 reactivation in these 18 patients. It should be emphasized that all five patients with fatal outcome and 10 patients with renal failure were in the HHV-6 reactivation group. CONCLUSIONS: A combination of immunological reaction to a drug and HHV-6 reactivation results in the severe course of DIHS. The demonstration of HHV-6 reactivation is a useful marker of diagnosis as well as prognosis in DIHS.     

Viral Infections Affecting the Skin in Organ Transplant Recipients

Viral skin infections are common findings in organ transplant recipients. The most important etiological agents are the group of human herpesviruses (HHV), human papillomaviruses (HPV), and molluscum contagiosum virus. HHV that are important in this group of patients are herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), HHV-6 and -7, and HHV-8, which causes Kaposi sarcoma (KS). HSV infections are characterized by their ability to establish latency and then reactivate at a later date. The most common manifestations of HSV infection in organ transplant recipients are mucocutaneous lesions of the oropharynx or genital regions. Treatment is usually with acyclovir, valaciclovir, or famciclovir. Acyclovir resistance may arise although the majority of acyclovir-resistant strains have been isolated from AIDS patients and not organ transplant recipients. In such cases, alternatives such as foscarnet, cidofovir, or trifluridine may have to be considered. VZV causes chickenpox as well as herpes zoster. In organ transplant recipients, recurrent herpes zoster can occur. Acute chickenpox in organ transplant patients should be treated with intravenous acyclovir. CMV infection occurs in 20-60% of all transplant recipients. Cutaneous manifestations, which include nonspecific macular rashes, ulcers, purpuric eruptions, and vesiculobullous lesions, are seen in 10-20% of patients with systemic infection and signify a poor prognosis. The present gold standard for treatment is ganciclovir, but newer drugs such as valganciclovir appear promising. EBV is responsible for some cases of post-transplant lymphoproliferative disorder, which represents the greatest risk of serious EBV disease in transplant recipients. HHV-6 and HHV-7 are two relatively newly discovered viruses and, at present, the body of information concerning these two agents is still fairly limited. KS is caused by HHV-8, which is the most recently discovered lymphotrophic HHV. Iatrogenic KS is seen in solid-organ transplant recipients, with a prevalence of 0.5-5% depending on the patient's country of origin. HPV is ubiquitous, and organ transplant recipients may never totally clear HPV infections, which are the most frequently recurring infections in renal transplant recipients. HPV infection in transplant recipients is important because of its link to the development of certain skin cancers, in particular, squamous cell carcinoma. Regular surveillance, sun avoidance, and patient education are important aspects of the management strategy.     

生殖器溃疡中单纯疱疹病毒的检测和分型

目的：了解性病门诊生殖器溃疡患者中单纯疱疹病毒（HSV）感染情况，并评价聚合酶链反应（PCR）－微孔板反向杂交检测和分型方法在生器疱疹诊断中的意义。方法：采用病毒分离培养、普通PCR和PCR－微孔板反向杂交法同时对200份生殖器溃疡标本作了HSV检测与分型。结果：PCR－微孔板反向杂交法的敏感性和特异性分别为98．1％和95．9％，PCR－微孔板杂交法分型结果与病毒分离培养法和普遍PCR的分型结果完全相符。生殖器溃疡中HSV检出率为30％（60／200），其中HSV－2感染占96．7％（58／60）。结论：HSV－2是性病门诊患者生殖器溃疡的主要病因之一，PCR－微孔板反向杂交法是一种适用生殖器溃疡标本中HSV的检测与分型的快速、敏感和特异的诊断方法。     

Influence of corticosteroid therapy on viral reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characteristically associated with sequential reactivation of herpesviruses, such as human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Since systemic corticosteroids are thought to result in viral reactivation due to their immunosuppressive effects, we clarified the influence of systemic corticosteroid therapy on viral reactivation in DIHS/DRESS. Viral DNA in peripheral whole blood and serum sIL-2R level were measured during the disease course in twenty DIHS/DRESS patients. Six of seven patients treated without corticosteroids experienced HHV-6 viremia associated with elevated serum sIL-2R levels. In contrast, high-dose corticosteroids started within 1 week after onset tended to inhibit the occurrence of HHV-6 reactivation with remarkable suppression of serum sIL-2R level. Low-dose corticosteroids or late-start high-dose corticosteroids did not suppress occurrence of HHV-6 viremia and the increase of sIL-2R levels. HHV-6 load in the blood was clearly correlated with the serum sIL-2R level. On the other hand, increased CMV load were found in patients treated with corticosteroids regardless of the start time. The frequency of detection of EBV DNA in peripheral blood was similarly observed in all groups. In conclusion, high-dose corticosteroids started within 1 week tended to suppress HHV-6 reactivation through suppression of T cell activation. However, CMV proliferation was promoted by corticosteroids regardless of the start time. These observations suggested that careful consideration should be given to the dose and timing of administration of systemic corticosteroids in the treatment of DIHS/DRESS.     

Case of vitiligo universalis as a sequela of drug‐induced hypersensitivity syndrome

Drug‐induced hypersensitivity syndrome (DIHS) is a type of severe drug adverse reaction with high morbidity and mortality. DIHS patients have been reported to subsequently develop autoimmune disease, which may be followed by end‐organ decompensation. We report a 47‐year‐old woman who presented with fever, generalized maculopapular eruption, facial edema and eosinophilia with liver function impairment after taking celecoxib and sulfasalazine for 1 month. The patient was diagnosed with definite DIHS. The patient was treated with immunosuppressants including systemic corticosteroid for approximately 1.5 years due to recurrent episodes. Reactivation of human herpesvirus 6 and possible reactivation of cytomegalovirus were detected. Generalized hypopigmentation of the skin and leukotrichia were noted 4 months after the onset of DIHS. Histopathological examination confirmed the diagnosis of vitiligo. Some spontaneous repigmentation was noted 4 years after DIHS without specific treatment. Further immunoserology study showed elevated plasma C‐X‐C motif chemokine 10 level, which is related to vitiligo activity, in our patient. The occurrence of widespread vitiligo after DIHS is an extremely rare condition. This case provides an important reminder for physicians to monitor such severe complications after DIHS.     

Cytomegalovirus neuritis in perineal ulcers

BACKGROUND: Although a range of cytomegalovirus (CMV)-induced cutaneous manifestations is described in AIDS patients, skin involvement in immunocompromised patients is rare, and intraneural CMV inclusions or CMV neuritis has not been documented in skin biopsies. METHODS AND RESULTS: Cutaneous biopsies of CMV lesions were collected prospectively for 12 months. The morphology, sites and symptomatology of the individual lesions, associated systemic illnesses, treatment schedules and disease outcome were recorded. A total of nine biopsies were obtained from three females who presented with extensive painful perineal ulceration and disseminated cutaneous ulcers, nodules and plaques. Clinically, herpes simplex virus (HSV) ulceration was diagnosed and treatment with acyclovir was initiated after biopsies from the natal cleft, perineum and neck were obtained. All were superficial and demonstrated HSV infection. Only the natal cleft biopsy demonstrated coexistent CMV inclusions. Suboptimal healing necessitated two further biopsies from each patient, none of which demonstrated HSV inclusions. Three of four deep perineal biopsies demonstrated CMV inclusions within nerves attended by a lymphocytic infiltrate and architectural disturbances. Two deep cutaneous biopsies of the trunk and abdominal wall confirmed CMV in extraneural locations only. One superficial perineal biopsy did not demonstrate any viral inclusion. CONCLUSIONS: In documenting CMV neuritis in painful perineal ulcers, the histopathological spectrum of perineal CMV ulcers is expanded, a cutaneous neurotropic characteristic of CMV is presented and a direct role for CMV in the pathogenesis of pain is suggested. CMV latency within perineal nerves is also revisited as another potential site of CMV reactivation in immunocompromised patients, and another potential site for possible venereal transmission of CMV infection. The exclusive presence of HSV in initial superficial biopsies highlights the need for optimally biopsied tissue to confirm the coexistence of CMV infection.