Extensive Disseminated Herpes Zoster in a Young Immunocompetent Male: A Rare Occurrence

Incidence and Risk of Postherpetic Neuralgia after Varicella Zoster Virus Infection in Hematopoietic Cell Transplantation Recipients: Hokkaido Hematology Study Group

Guidelines of care for dermatologic conditions in patients infected with HIV

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.

Varicella Zoster Virus (VZV) in Solid Organ Transplant Recipients

Introduction: Disseminated herpes zoster (HZ) is uncommon and typically occurs in immunocompromised populations, including patients with HIV/AIDS, transplantation recipients, and patients with autoimmune diseases. However, disseminated HZ may also occur in healthy patients. Many studies have found that its incidence is positively correlated with age, and the severity is also positively correlated with age. Central nervous system (CNS) complications during or following HZ are extremely rare. Encephalitis has been reported to affect only 0.1%–0.2% of HZ patients. The occurrence of disseminated HZ with acute encephalitis in immunocompetent patients is even less frequently reported. Case Presentation: An 85-year-old male presented with disseminated HZ and acute encephalopathy, later confirmed as varicella zoster virus (VZV) encephalitis via cerebrospinal fluid analysis and neuroimaging. Treatment with intravenous acyclovir and methylprednisolone led to gradual improvement in consciousness, and the skin lesions regressed, though dizziness persisted. Conclusion: Elderly patients with disseminated HZ should be closely monitored for potential neurological complications such as HZ encephalitis. Once clinical manifestations such as fever, headache, meningeal irritation, cranial nerve impairment, or even cognitive changes appear, the possibility of CNS infection should be suspected.

Objective To investigate the predisposing factors and clinical features of disseminated herpes zoster, and to explore factors influencing postherpetic neuralgia. Methods Clinical data were collected from 53 patients with disseminated herpes zoster and 809 patients with common herpes zoster between 2012 and 2015, and analyzed retrospectively. Logistic regression analysis was used to assess factors influencing the occurrence of and pain intensity in disseminated herpes zoster, as well as the occurrence of postherpetic neuralgia. Results No significant difference in patients′ age was observed between the disseminated and common herpes zoster groups (56.66 ± 17.24 vs. 56.50 ± 15.51 years, t = 0.071, P > 0.05) , but there was a significant difference in the gender ratio between the two groups (χ2 = 8.16, P = 0.004). The incidence rates of bullae, pustules and fever were all significantly higher in the disseminated herpes zoster group than in the common herpes zoster group (15.09% vs. 3.58%, χ2 = 16.04, P < 0.01; 47.17% vs. 26.82%, χ2 = 10.20, P < 0.01; 30.19% vs. 8.03%, χ2 = 28.68, P < 0.01). The disseminated herpes zoster group also showed significantly higher pain scores at admission compared with the common herpes zoster group (Median [P25-P75]: 6 [4-7.5] vs. 5[3-7], Z = -3.460, P = 0.001). Logistic regression analysis revealed that gender, age, fatigue and HIV infection were significantly associated with the occurrence of disseminated herpes zoster (all P < 0.05). Additionally, HIV infection (OR = 5.570, 95% CI: 1.196-25.939, P = 0.029) , gender (OR = 0.166, 95% CI: 0.029 - 0.945, P = 0.043) , age (OR = 1.064, 95% CI: 1.010-1.119, P = 0.019) and the number of days that antiviral therapy lasted (OR = 0.669, 95% CI: 0.505-0.885, P = 0.005) were all factors influencing the occurrence of postherpetic neuralgia. Conclusion Male, old age, fatigue and especially HIV infection are risk factors for the occurrence of disseminated herpes zoster, and male, old age and antiviral therapy duration may be associated with the occurrence of postherpetic neuralgia. Key words: Herpes zoster; Logistic models; Neuralgia, postherpetic

Objective To explore the treatment for malignant tumors complicated with disseminated herpes zoster, and then compare with malignant tumors complicated with unilateral herpes zoster.Methods The data on 9 patients with malignant tumors and complicated with disseminated herpes zoster who had been treated from January 2000 to July 2011 were retrospectively analyzed,and so were the data on the 28 patients complicated with unilateral herpes zoster herpes zoster who had been treated during the same time.Results There was a significant difference in the CD4/CD8 rate between the patients with disseminated herpes zoster and those with unilateral herpes zoster ( 44.44％ vs.10.71％ or 4/9 vs.3/28,P ＜ 0.05 ).Time to scar formation differed significantly between the patients with disseminated herpes and those with unilateral herpes zoster ( [7.44 ± 1.926]d vs.[3.89 ± 0.598]d,P＜0.01 ).Conclusions The immune function is weaker in malignant tumor patients complicated with disseminated herpes zoster than in those with local herpes zoster.Time to scar formation is also longer in the patients with disseminated herpes zoster. Key words: Malignant tumors; Disseminated Herpes zoster; Treatment

Disseminated herpes zoster can present with a wide range of clinical manifestations, including visceral involvement. This case report describes an 89-year-old male who presented with severe abdominal pain, initially without any cutaneous lesions, leading to diagnostic challenges. The patient had acute-onset right lower abdominal pain that was persistent and worsened with movement. Initial diagnostic imaging revealed mild peritoneal edema over the ascending colon without evidence of bowel obstruction, vascular abnormalities, or free air. Due to the severity of the pain, symptomatic treatment was administered. Subsequently, a vesicular rash appeared on the right flank, corresponding to the pain site. This led to the diagnosis of disseminated herpes zoster with peritonitis. Antiviral therapy with intravenous acyclovir was initiated promptly, resulting in clinical improvement. However, postherpetic neuralgia (PHN) developed and required ongoing pain management. This case underscores the importance of including disseminated herpes zoster in the differential diagnosis of acute abdominal pain, particularly in elderly and immunocompromised patients. The absence of an initial rash can delay diagnosis, increasing the risk of complications. Early recognition and antiviral therapy prevent disease progression and improve patient outcomes. Moreover, PHN remains a significant concern, emphasizing the need for effective pain management and preventive strategies, including vaccination. Raising awareness among healthcare providers about atypical presentations of herpes zoster can facilitate early diagnosis and timely intervention, ultimately enhancing patient care.

An HIV-infected patient with acute retinal necrosis as immune reconstitution inflammatory syndrome due to varicella-zoster virus.

Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV)

We report three HIV-infected children with bilateral progressive outer retinal necrosis caused by varicella-zoster virus. All three lost vision in both eyes. Aggressive treatment strategies with combination intravenous antiviral therapy in addition to intravitreal antiviral therapy and appropriate surgical management may prevent blindness. Rapid recognition of this distinct clinical syndrome is essential to improve visual outcome.

Background: Solid organ transplant recipients (OTR) are at increased risk for herpes zoster (HZ), primarily due to immunosuppressive medication. HZ may cause to serious complications including cutaneous dissemination, postherpetic neuralgia (PHN), involvement of visceral organs, encephalitis and death. Methods: We retrospectively analyzed solid OTR who have developed HZ in between December 2018 and December 2019. Medical records were reviewed to assess the clinical characteristics and outcome of HZ in those patients. Additionally, patients with severe pain who had required opioid analgesics and/or gabapentin were called back for follow up examination. Results: There were 16 patients (Eight males and eight females) with a mean age of 43 (range, 11-58 years). Thirteen (81%) patients were renal transplant recipients, whereas three (19%) were cardiac transplant recipients. Median time from organ transplantation to onset of HZ was 39.5 months (range, 5.4-254.6 months). Visceral disease or mortality did not occur in any of the patients. Most common (69%) complaint was pain. Four patients (25%) were asymptomatic, and presented only with skin lesions. Thoracic region (9 patients) was the most common localization followed by genital-gluteal (4 patients), lower extremity (one patient), and ophthalmic region (one patient). Vesicles (75%) were the most common clinical presentation. Distribution of lesions was in single dermatome in 13 (81%) patients. One patient additionally had scattered vesicles adjacent to the primary dermatome, and two had scattered vesicles (<20) distant to the primary dermatome. Nine (56%) patients had received rejection treatment before the diagnosis of HZ. Majority (87.5%) of patients were on triple immunosuppressive regimen at the onset of HZ. For the treatment of HZ, four (%25) patients received outpatient treatment with oral valacyclovir therapy. Ten (62.5%) patients were hospitalized for the first few days (due to renal dysfunction, severe skin lesions, presence of lesions outside the primary dermatome, severe pain, or living out-of-town), and continued with oral antiviral therapy when discharged. One renal transplant patient with ophthalmic HZ and one cardiac transplant patient with hypoxic brain injury completed the antiviral treatment (intravenous acyclovir) in hospital. Renal dose adjustment was done in 8 (50%) patients. The doses of immunosuppressive drugs were reduced only in two cardiac transplant patients. Although 8 (%50) patients required potent analgesic treatment including opioid analgesics and/or gabapentin in the acute phase, only one that had ophthalmic HZ developed PHN. Among patients with severe pain, the longest duration of pain was 1.5 months. The patient with ophthalmic HZ later presented with transient third and sixth cranial nerve palsy without venous thrombosis and brain involvement. Conclusion: With prompt initiation of patient-adjusted therapy, post-transplant HZ seems most likely to have a favorable course. Prospective studies including large number of OTR and immunocompetent individuals with HZ are needed.

Herpes zoster classical clinical presentation is the acute onset of multiple vesicles over an erythematous base, disposed over one or two dermatomes with up to 20 vesicles located outside the main dermatome. Disseminated herpes zoster is an atypical and rare form of presentation of herpes zoster, which manifests with lesions beyond the described territory. It occurs mainly in patients with some type of cellular immunosuppression. The diagnosis is made with the medical history and physical examination, however, it should be confirmed with laboratory tests. Treatment must be initiated early to avoid serious complications, such as bacterial infection of the lesions, post-herpetic neuralgia, or even central nervous system involvement. The drug of choice is intravenous acyclovir that must be maintained until the cessation of the appearance of new lesions, and then switch to its oral presentation for another 5-7 days. Disseminated herpes zoster mortality rounds 5-15%. There are varicella-zoster virus vaccines, that have been shown to reduce the incidence of herpes zoster relapses, however its utility to disseminated herpes zoster is uncertain and further studies are required. We present the case of a male patient with a history of rheumatoid arthritis who consults with multiple vesicles distributed throughout his body.

Incidence and Risk of Post-Herpetic Neuralgia after Varicella Zoster Virus (VZV) Infection in Hematopoietic Cell Trasnplantation (HCT) Recipients.

Background Patients with ulcerative colitis (UC) and patients with multiple sclerosis (MS) have an elevated risk of developing herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV). Increased incidence of HZ has been reported with sphingosine, 1-phosphatase (S1P) receptor modulators. This analysis examined the number of patients who failed screening due to a lack of demonstrated VZV immunity and the incidence of HZ from completed phase, 3 ozanimod clinical trials. Methods Safety results were included from True North (52-week trial) in patients with UC, and SUNBEAM (12-month trial), and RADIANCE (24-month trial) in patients with MS. All patients were required to have had a positive VZV IgG antibody status or completed VZV vaccination ≥30 days prior to randomization based on known effects of S1P modulators. Patients with a negative VZV antibody titer could choose to receive the VZV vaccination to qualify for the trial. Number of pre-screen failures because of lack of demonstrated immunity, occurrence of HZ, and association between HZ cases and lymphopenia were analyzed. Results Of, 1831 patients with UC screened for VZV immunity, 104 (5.7%) failed screening due to lack of documentation of VZV antibody or VZV vaccination ≥30 days before randomization;, 22% (23/104) subsequently received varicella vaccination and were rescreened and enrolled. Of, 3332 MS patients tested for VZV immunity, 309 (9.3%) tested negative and, 32% (98/309) of these patients were vaccinated prior to randomization. In the UC and MS trials, the incidence of HZ cases was low in ozanimod-treated patients (8 cases [1.0%] and, 5 cases [0.6%], respectively; Table, 1). All cases were distributed across a single dermatome, did not result in a complication of HZ, and were treated with oral antivirals while patients remained on ozanimod. None of the patients discontinued ozanimod because of HZ and none of the HZ cases were associated with grade, 4 lymphopenia (defined as an absolute lymphocyte count &amp;lt;0.2 x, 109/L). Conclusion In the ozanimod phase, 3 UC and MS trials, 5%–10% of patients screened did not have demonstrated VZV immunity;, 22%–32% of these patients received varicella vaccination, were rescreened and enrolled. The overall HZ incidence in clinical trials was low (≤1% of patients), all cases were distributed across a single dermatome, and no serious or complicated cases occurred in ozanimod-treated patients with VZV immunity. Additional studies are warranted to evaluate the incidence of HZ in clinical practice.