Risk of herpes simplex virus infection in solid organ transplant recipients: A population-based cross-sectional study.

BACKGROUND: Herpes simplex virus (HSV) is an opportunistic infection antigen in solid organ transplant (SOT) recipients. However, this phenomenon has received limited attention from epidemiologists. Our study aims to determine the HSV infection risk in SOT recipients. METHODS: This was a nationwide population-based cross-sectional study based on the National Health Insurance Research Database from 2002 to 2015. We used propensity score matching to avoid selection bias and analyzed the association between HSV infection and SOT recipients with multiple logistic regression analysis. RESULTS: At a 3-year follow-up, SOT recipients had a higher risk of developing HSV, with an adjusted odds ratio (aOR) of 3.28 (95% confidence interval (CI), 2.51-4.29). Moreover, at 6-month, 1-year, and 2-year follow-ups, SOT recipients also had an increased risk of HSV than general patients with aORs of 3.85 (95% CI, 2.29-6.49), 4.27 (95% CI, 2.86-6.36), and 3.73 (95% CI, 2.74-5.08), respectively. In the subgroup analysis, lung transplant recipients (aOR = 8.01; 95% CI, 2.39-26.88) exhibited a significantly higher chance of HSV among SOT recipients, followed by kidney transplant recipients (aOR = 3.33; 95% CI, 2.11-5.25) and liver transplant recipients (aOR = 3.15; 95% CI, 2.28-4.34). CONCLUSION: HSV can develop at any time after organ transplantation. SOT recipients had a higher risk of HSV infection than the general population at 6 months, 1 year, 2 years, and 3 years after transplantation, with the highest chance at 1 year after. In addition, the patients who underwent lung transplantion were at higher risk for HSV infection than liver or kidney transplant recipients.

Reactivation of Herpes Simplex Virus Following Sphenopalatine Ganglion Nerve Block: Case Report and Review of the Literature.

A 36-year-old woman with no significant past medical history underwent a sphenopalatine ganglion block for treatment of a month-long migraine headache refractory to conservative treatment protocols. The headache resolved initially, but 1 day following the procedure, the headache recurred. The patient also developed an erythematous and edematous rash which cultures confirmed to be herpes simplex virus (HSV). Following several unsuccessful treatment modalities, the patient received valacyclovir, which resulted in resolution of her headache. Underlying HSV-1 infection may cause intractable migraine headache and nerve blocks may potentiate reactivation of latent HSV infection that caused the skin lesion in this case.

Two Cases of Herpes Gladiatorum Identified in a Korean Middle-School Wrestling Team: A Case Report.

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Risk factors of facial herpes simplex after percutaneous microballoon compression for trigeminal neuralgia: A retrospective case-cohort study..

BACKGROUND: Percutaneous microballoon compression (PMC) is an important clinical technique for the treatment of trigeminal neuralgia (TN). Some studies have shown that patients may be infected with herpes simplex virus type 1 (HSV-1) after surgery. However, the prevalence and associated risk factors are unclear yet. This study aimed to explore the potential risk factors of facial herpes simplex (FHS) in patients with TN treated by PMC retrospectively. METHODS: A retrospective study included 181 patients with TN undergoing PMC treatment between September 2019 and August 2020 in Sichuan Cancer Hospital and Institute. Depending on whether the patient was infected with HSV-1 after PMC operation or not, the patients were divided into two groups, FHS group and non-FHS group, respectively. Demographic, clinical, laboratory, and surgical data of the patients were collected. Univariable and multivariable logistic regression analysis were used to explore the risk factors of infecting with HSV-1 in patients with TN after PMC. RESULTS: Among 181 patients with TN treated by PMC surgery without FHS. 49 patients were diagnosed with FHS after operation, and the diagnosis was confirmed by PCR detection of HSV-1. All patients had no FHS before operation, the occurrence of FHS was 27.07% (49/181) in patients underwent PMC. Variables with p<0.05 in univariable analysis included gender (male/female), age, duration of disease and CD8+ T cells count. The results of multivariable logistic regression analysis showed the independent risk factors of FHS after PMC were gender (male/female) (p<0.01, OR 0.061, 95% CI 0.009~0.428), age (p<0.001, OR 1.169, 95% CI 1.065~1.283), duration of disease (p<0.001, OR 1.361, 95% CI 1.206~1.535) and CD8+T cells count (p<0.01, OR 0.993, 95% CI 0.989~0.998). CONCLUSIONS: In our study, we found that elderly patients and duration of disease were the risk factors of occurring FHS in TN patients after PMC surgery. CD8+T cells count and male gender were the protective factors for not developing FHS.

Disseminated cutaneous herpes simplex infection after COVID-19 vaccination in a rheumatoid arthritis patient: a case report and review.

Since COVID-19 vaccination started in December 2020, different side effects were reported. This case report describes the possibility of developing disseminated herpes simplex infection after COVID-19 vaccine in a patient with rheumatoid arthritis. In this case report, we describe a 63-year-old Iranian female. She was a known case of seronegative rheumatoid arthritis and presented with generalized papulo-pustular itchy and painful skin lesions which appeared about seven days after the second dose of Sinopharm BIBP COVID-19 vaccine (BIBP-CorV). A biopsy of the skin lesions revealed acantholysis, neutrophils, and enlarged keratinocytes with eosinophilic intra-nuclear inclusions. Findings were consistent with herpes simplex infection. She was successfully treated by acyclovir. Disseminated cutaneous herpes simplex infection may have been triggered by COVID-19 vaccination. Reactivation of herpes virus after COVID-19 vaccines was reported in both rheumatic patients and other individuals. Whether having an underlying autoimmune inflammatory disorder could be an additional risk factor is still unknown.

An Unusual Pediatric Manifestation of the Herpes Simplex Virus.

Herpetic whitlow is a viral infection of the fingers or toes caused by the herpes simplex virus. Herpes simplex virus is a common pathogen that causes infections in any cutaneous or mucocutaneous surface, most commonly gingivostomatitis or genital herpes. However, infection of the digits is also infrequently reported. Herpetic whitlow occurs when the virus infects the distal phalanx of the fingers or toes by means of direct inoculation, causing pain, swelling, erythema, and vesicle formation. The proper diagnosis is important because the condition can mimic various other podiatric abnormalities such as paronychia, bacterial cellulitis, or even embolic disease. Improper diagnosis often leads to unnecessary work-up, antibiotic therapy, or even surgical intervention. This case will help illuminate the clinical presentation of herpetic whitlow in an atypical location, and the patient's subsequent treatment. We present an atypical case of right hallux herpetic whitlow with delayed diagnosis and associated cellulitis. The patient was admitted after seeing multiple providers for a progressive right hallux infection that presented as a mixture of vesicular lesions and apparent cellulitis. His history was positive for biting his fingernails and toenails, and the lesions were noted to be honeycomb-like, with minimal drainage. The lesions were then deroofed and viral cultures were obtained, which were positive for herpes simplex virus type 1, thus confirming a diagnosis of herpetic whitlow. Although he remained afebrile with negative wound cultures during admission, a secondary bacterial infection could not be excluded because of his nail avulsion and surrounding cellulitis. He was discharged on oral antibiotics, antivirals, and wound care recommendations. Herpetic whitlow should be included in the differential diagnosis of pedal digital lesions that appear as vesicular or cellulitic in the pediatric population.

Dermatitis during Spaceflight Associated with HSV-1 Reactivation.

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.

Outcomes of Herpes Simplex Virus Pneumonitis in Critically Ill Patients.

Critically ill patients, such as those in intensive care units (ICUs), can develop herpes simplex virus (HSV) pneumonitis. Given the high prevalence of acute respiratory distress syndrome (ARDS) and multiple pre-existing conditions among ICU patients with HSV pneumonitis, factors predicting mortality in this patient population require further investigation. In this retrospective study, the bronchoalveolar lavage or sputum samples of ICU patients were cultured or subjected to a polymerase chain reaction for HSV detection. Univariable and multivariable Cox regressions were conducted for mortality outcomes. The length of hospital stay was plotted against mortality on Kaplan-Meier curves. Among the 119 patients with HSV pneumonitis (age: 65.8 ± 14.9 years), the mortality rate was 61.34% (73 deaths). The mortality rate was significantly lower among patients with diabetes mellitus (odds ratio [OR] 0.12, 95% confidence interval [CI]: 0.02-0.49, p = 0.0009) and significantly higher among patients with ARDS (OR: 4.18, 95% CI: 1.05-17.97, p < 0.0001) or high (≥30) Acute Physiology and Chronic Health Evaluation II scores (OR: 1.08, 95% CI: 1.00-1.18, p = 0.02). Not having diabetes mellitus (DM), developing ARDS, and having a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independent predictors of mortality among ICU patients with HSV pneumonitis.

Human genetic polymorphisms and risk of viral infection after solid organ transplantation.

The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomegalovirus (CMV) infection or disease has been attributed to certain SNPs in TLR9 or IFNL3 genes, whereas the opposite effect has been attributed to genetic polymorphisms in TLR2, MBL2, DC-SIGN, IL10 or IFNG. The presence of SNPs in other molecules not directly involved in innate or adaptive immune responses such as aquaporins or pregnane X appear to modulate the risk of CMV or BK polyomavirus infection, respectively. Little information is available on the genetic determinants of the post-transplant susceptibility to herpesviruses causing clinical infection (herpes simplex virus or varicella zoster virus) or the replication kinetics of components of the human blood virome used as immune surrogates (Torque teno virus). The present review critically summarizes the current knowledge on how SNP genotyping would be useful to stratify SOT recipients according to the individual risk of viral infection and proposes next research steps. Genetic susceptibility testing may improve personalized medicine and contribute to minimize the risk of viral infection after SOT.

Distinguishing Features Common to Dual Fatal Herpes Simplex Virus Infections That Occur in Both a Pregnant Woman and Her Newborn Infant.

Deaths from herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are rare. A major exception is perinatally acquired HSV-1 or HSV-2 infection where the neonatal death rate is substantial. Fatal HSV infection also occurs occasionally in pregnant women. The goal of this review is to enumerate the reports that describe dual deaths of both a pregnant woman and her newborn from a herpesvirus infection. A total of 15 reports were found in the medical literature, of which five described pregnant women with HSV encephalitis and 10 described women with disseminated HSV infection. When the virus was typed, most cases of dual mother/newborn deaths were caused by HSV-2. Of interest, in two situations caused by HSV-1, the pregnant woman probably acquired her primary HSV-1 infection from one of her children and not by sexual transmission. Complete genomic sequencing was performed on one set of HSV-1 isolates collected from mother (blood) and newborn (blood and skin). The mother's strain and the newborn's skin strain were 98.9% identical. When the newborn's two strains were compared, they were 97.4% identical. Only one mother was tested by the HerpeSelect IgG antibody kit. During the nine days of her undiagnosed disseminated infection preceding her death, her serology was negative. In summary, although dual mother/newborn deaths from HSV infection are rare, they continue to be reported as recently as 2017.

Darier disease, radiation therapy, and herpesvirus -- an unfortunate triad.

Darier disease (DD) is a rare autosomal dominant keratinizing disorder often characterized by brown scaly pruritic papules over the face, neck, and trunk. Herein is reported a patient who developed secondary cutaneous herpes simplex virus (HSV) following exacerbation of his DD as a result of radiation therapy. In November 2020, a 78-year-old man presented to clinic for a pruritic rash on his back consistent with DD. He had developed the rash after the conclusion of chemoradiation therapy for recently diagnosed urothelial carcinoma of the bladder with squamous differentiation. However, he returned two weeks later complaining of a marked worsening of the rash associated with a pain and burning sensations. Histopathology was non-conclusive, but the lesions were found to be positive for HSV-1 by PCR. The patient recovered without complication over a period of two weeks following a course of valacyclovir. There is precedent in the literature for ionizing radiation inducing flares of DD lesions in overlying skin. In addition, DD has been shown to put a patient at increased risk for secondary infections such as HSV. This case report demonstrates that HSV could pose a significant risk to those with DD receiving radiation therapy and thus could warrant prophylactic treatment.

High rate of HSV-1 reactivation in invasively ventilated COVID-19 patients: Immunological findings.

SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome with the need of invasive ventilation. Pulmonary herpes simplex-1 (HSV-1) reactivation in invasively ventilated patients is a known phenomenon. To date very little is known about the frequency and the predisposing factors of HSV-1 reactivation in COVID-19. Therefore, we evaluated our cohort of invasively ventilated COVID-19 patients with severe pneumonia for HSV-1 in respiratory specimens and combined these results with functional immunomonitoring of the peripheral blood. Tracheal secretions and bronchial lavages were screened by PCR for HSV-1 positivity. Comprehensive immunophenotyping and quantitative gene expression analysis of Interferon-stimulated genes (IFI44L, MX1, RSAD2, ISIG15 and IFIT1) and IL-1 beta were performed in whole blood. Time course of infection beginning at symptom onset was grouped into three phases ("early" phase 1: day 1-10, "middle" phase 2: day 11-30 and "late" phase 3: day 31-40). Pulmonary HSV-1 reactivation was exclusively observed in the later phases 2 and 3 in 15 of 18 analyzed patients. By FACS analysis a significant increase in activated CD8 T cells (CD38+HLADR+) in phase 2 was found when compared with phase 1 (p<0.05). Expression of Interferon-stimulated genes (IFI44L, RSAD2 ISIG15, MX1, IFIT1) was significantly lower after HSV-1 detection than before. Taken together, reactivation of HSV-1 in the later phase of SARS-CoV-2- infection occurs in parallel with a drop of antiviral innate responsiveness as shown by decreased expression of Interferon-stimulated genes and a concurrent increase of highly activated CD38+HLADR+ CD8 T cells.

COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.

The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.

Routine testing for herpes simplex virus in bronchoalveolar lavage specimens is unwarranted.

Herpes simplex virus (HSV) infections of the lung are rare, but HSV is occasionally detected in bronchoalveolar lavage (BAL) specimens. We assessed whether routinely performing HSV PCR tests in BAL specimens is warranted. HSV was detected in 7% (52/722) of BALs. In 47% of HSV-positive patients a typical respiratory virus or pathologic microorganism was identified. Oral HSV reactivation was identified in 27%; however, anti-HSV therapy was initiated in just three patients following the positive HSV test. Patients undergoing BAL for transplant surveillance received anti-HSV prophylaxis more often than those with acute respiratory failure, but both groups did not differ significantly in terms of patient outcome or co-infections. No patient was diagnosed with HSV pneumonia. These findings suggest that positive HSV PCR results in BAL specimens most commonly represents contamination from oral HSV reactivation, and that HSV PCR should be ordered selectively, rather than routinely, as part of a test panel.

Selective downregulation of natural killer activating receptors on NK cells and upregulation of PD-1 expression on T cells in children with severe and/or recurrent Herpes simplex virus infections.

Severe, recurrent or atypical Herpes simplex virus (HSV) infections are still posing clinical and diagnostic problem in clinical immunology facilities. However, the molecular background of this disorder is still unclear. The aim of this study was to investigate the expression of activating receptors on NK cells (CD16, NKp46, NKG2D, NKp80, 2B4, CD48 and NTB-A) and checkpoint molecule PD-1 on T lymphocytes and NK cells, in patients with severe and/or recurrent infections with HSV and age-matched healthy control subjects. As a result, we noticed that patients with severe and/or recurrent infection with HSV had significantly lower percentage of CD16brightCD56dim and higher percentage of CD16dimCD56bright NK cell subsets, when compared to control subjects, which may be associated with abnormal NK cell maturation during chronic HSV infection. Patients had also significantly downregulated expression of CD16 receptor on CD16bright NK cells. The expression of activating receptors was significantly reduced on patients' NK cells - either both the percentage of NK cells expressing the receptor and MFI of its expression (NKp46, NKp80 and 2B4 on CD16brightCD56dim cells and NKp46 on CD16dimCD56bright cells) or only MFI (NKG2D on both NK cell subsets). It should be noted that the reduction of receptor expression was limited to NK cells, since there was no differences in the percentage of receptor-positive cells or MFI on T cells. However, NTB-A receptor was the only one which expression was not only simultaneously changed in patients' NK and T cells, but also significantly upregulated on CD16dimCD56bright NK cell and CD8+ cell subsets. Patients had also upregulated proportion of CD4+ T cells expressing PD-1. Thus, we suggest that an increased percentage of PD-1+ cells may represent an independent indirect mechanism of downregulation of antiviral response, separate from the reduction of NK cell activating receptors expression. Altogether, our studies indicate two possible mechanisms which may promote perpetuation of HSV infection: 1) selective inhibition of activating receptors on NK cells, but not on T cells, and 2) upregulation of checkpoint molecule PD-1 on CD4+ T cells.

Delineating the Role of Serum Immunoglobulin Titers in Burn Patients at High Risk for Herpes Simplex Virus Infection.

Herpes simplex virus (HSV) is common in the population and reactivation of latent infection often occurs in times of physiologic stress, including postburn injury. Active HSV infection complicates burn injury recovery and increases morbidity. A retrospective chart review of high-risk burn patients (≥20%TBSA and/or facial burns) who had screening HSV immunoglobulin titers drawn from 2015 to 2018 was conducted. Titer levels and morbidity-related outcomes were compared between patients who developed active infection and those who did not. Fifty-six patients had serum HSV titers measured. Twenty-nine patients (52%) developed clinical signs of HSV infection, almost all of which (97%) suffered facial burns. Titers were ordered on median hospital day 1.5 (0.00-4.0) and infection occurred on day 8.0 (2.0-16). Median HSV-1,2 IgM titers were significantly increased in patients who developed clinically active HSV infection (0.71 [0.44-1.1] vs 0.52 [0.34-0.74], P = .02). Median HSV-1 IgG (P = .65) and HSV-2 IgG titers (P = .97) were not different between groups. Patients who developed active infection had a comparable hospital length of stay (27 [9.5-40] days vs 20 [8.0-28] days, P = .17) and ICU length of stay (26 [13-49] days vs 19 [11-27] days, P = .09) to those who did not develop infection. There was no difference in mortality. Increased HSV-1 and 2 IgM screening levels were associated with an increased risk of developing active HSV infection, and offer a specific screening modality in high-risk patients. Elevated IgM titers warrant further consideration for administration of HSV prophylaxis, as earlier intervention may prevent infection onset and minimize morbidity.

Postnatal Exposure to Herpes Simplex Virus: To Treat or Not to Treat?

Neonatal herpes simplex virus (HSV) infection carries significant morbidity and mortality. In contrast to perinatal exposure, there are no clear guidelines for the management of postnatal HSV exposure. This review focuses on the risk of HSV infection following postnatal exposure and suggests an approach to management. While many infants are protected by transplacentally transferred maternal anti-HSV antibodies, infants of seronegative mothers with significant postnatal HSV exposure may be at risk of severe disease. Individual risk assessment, appropriate investigations, and empiric acyclovir treatment should be considered in postnatally exposed newborns, even if asymptomatic. In all cases, close clinical follow-up is indicated, as well as education of families on the symptoms of neonatal HSV disease. Finally, measures to reduce the risk of postnatal HSV infection should be considered, such as discouraging individuals, particularly those with a history of recurrent cold sores, from kissing newborns.

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis.

BACKGROUND: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials. OBJECTIVE: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis. METHODS: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy. RESULTS: Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%. LIMITATIONS: Limited data in terms of size and follow-up time were available. CONCLUSION: Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events.

Herpes simplex virus type 2 myelitis mimicking ICU-acquired weakness as a complication of meningococcal meningitis: A case report.

Herpes simplex virus 2 (HSV-2) is a well-known cause of neurological complications. This case study describes the first reported case of reactivated HSV-2 myelitis, which was induced by immunosuppression due to sepsis. During the treatment of meningococcal meningitis, the patient developed quadriparesis and was later diagnosed as HSV-2 myelitis, mimicking ICU-acquired weakness. The case emphasizes the importance of excluding viral myelitis before making the diagnosis of ICU-acquired weakness.

Topical Treatment of Acyclovir-Resistant Herpes Simplex Virus Stomatitis after Allogeneic Hematopoietic Cell Transplantation.

INTRODUCTION: We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT). PATIENTS: HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir. RESULTS: Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived. CONCLUSIONS: ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.