Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

BACKGROUND AND PURPOSE: Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. METHODS: For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. RESULTS: In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. CONCLUSION: These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

Erythema multiforme: Differences between HSV-1 and HSV-2 and management of the disease-A case report and mini review.

Erythema multiforme (EM) is an immune-mediated reaction characterized by target lesions and with possible mucosal involvement. Its most frequent cause is HSV, with HSV-1 more common than -2. It is usually self-limited but it can show recurrences. We report a peculiar case of recurrent herpes-associated erythema multiforme (HAEM) in a 35-year-old man. The patient was affected by both herpes labialis and genitalis, but the typical target lesions were only associated with recurrent herpes labialis. Here, we hypothesize about the pathogenic differences between HSV-1 and HSV-2, and discuss the therapeutic management of HAEM.

Recurrent herpes labialis in the pediatric population: Prevalence, therapeutic studies, and associated complications.

Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English-language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under- or over-estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.

Recurrent Herpes Labialis in Adults: New Tricks for an Old Dog.

Herpes labialis remains a common worldwide affliction. Recent advances in understanding the basic pathogenesis have led to new therapeutic intervention, both on-label and off-label. Aside from reducing the duration and symptomatology of acute outbreaks, another goal of treatment is to decrease the frequency of future episodes. Oral and topical acyclovir and its analogues are the mainstay of both chronic suppressive and episodic therapy. A new muco-adhesive formulation of acyclovir provides a decrease in outbreaks, probably due to a diminution of herpesvirus load in all reservoir sites. Acyclovir-resistant strains are rare in immunocompetent hosts; parenteral foscarnet and cidofovir are administered in this situation. Parenteral acyclovir is the drug of choice for eczema herpeticum, which may begin as herpes labialis in an atopic dermatitis patient. Thermotherapy may be beneficial, and a certified device to deliver heat is available outside the United States.

J Drugs Dermatol. 2017;16(3 Suppl):s49-53.

Postherpetic Nevocentric Erythema Multiforme.

A previously healthy 35-year-old Caucasian woman presented with abrupt onset of erythematous, mildly pruritic plaques surrounding the majority of the nevi present on her neck, chest, back, and upper and lower extremities. She denied history of any recent systemic illnesses and was not taking any medications. On further questioning, the patient reported a recent episode of recurrent herpes labialis 2 weeks prior. The patient has a Fitzpatrick type I skin type with more than 100 brown and reddish brown pigmented macules and papules over her entire body. Plaques ranged in size from 0.4 cm to 1.5 cm depending on the size of the corresponding nevus. The patient's skin was examined in its entirety, and there were no lesions suspicious for melanoma. Two biopsies were performed from the patient's back: one from the nevus itself and another from the surrounding erythematous plaque. The nevocentric erythematous plaques were visible for approximately 1 week at which time they gradually disappeared without treatment. As these areas improved, the patient noticed targetoid lesions on the dorsal hands without associated nevi. Two weeks later, the targetoid lesions had spontaneously resolved.

Clinical and cytologic features of antibiotic-resistant acute paronychia.

BACKGROUND: Acute paronychia usually is treated as a bacterial infection, but antibiotic-resistant acute paronychia may be caused by other infectious and noninfectious problems. OBJECTIVE: We sought to describe the clinical, etiologic, cytologic, and therapeutic features of antibiotic-resistant acute paronychia. METHODS: A retrospective review of medical records and cytology was performed in 58 patients (age, 1 month-91 years; 36 children and adolescents [62%] and 22 adults [38%]) who had antibiotic-resistant acute paronychias. RESULTS: Causes of paronychia included bacteria (25 patients [43%]), viruses (21 patients [36%]), fungi (5 patients [9%]), drugs (3 patients [5%]), pemphigus vulgaris (3 patients [5%]), and trauma (1 patient [2%]). Diagnostic cytologic findings were noted in 54 patients (93%); no diagnostic cytologic findings were present with drug-induced (3 patients) or traumatic (1 patient) paronychia. The most common predisposing factors were the habits of finger- or thumb-sucking (14 patients [24%]) and nail-biting (11 patients [19%]). Complications included id reaction with erythema multiforme in 3 patients (5%). LIMITATIONS: Limitations include retrospective study design from 1 treatment center. CONCLUSION: Antibiotic-resistant acute paronychia may be infectious or noninfectious. Cytologic examination with Tzanck smear may be useful diagnostically and may prevent unnecessary use of antibiotics and surgical drainage.

[Using cycloferon in the complex treatment of herpetic infection in patients with atopic dermatitis].

Clinical efficacy of including cycloferon liniment in combined treatment of herpetic infection in a group of 40 patients with atopic dermatitis has been analyzed. It is concluded that the administration of cycloferon favors dynamic disappearance of general infectious syndrome, reduces timeline of rash as well as length of local inflammation, accelerates epithelization of erosions (on the average 1.2 - 1.4 times, p < 0.05), decreases frequency of recurrent infections, and reduces the level of pro-inflammatory cytokines in the blood of patients.

The impact of HSV for inflammatory arthropathy patients.

Herpes simplex virus type 1 (HSV-1), also known as herpes labialis, is the etiologic agent of vesicular lesions of the oral mucosa commonly referred to as "cold sores". HSV-1 can also cause clinical disease in a wide variety of other anatomic locations including the genitalia, liver, lung, eye, and central nervous system. These infections can be severe, particularly in the setting of immunosuppression, such as inflammatory arthropathy patients on Methotrexate ± biological therapies. Here, we highlight the importance of physician awareness of HSV due to its potential impact for rheumatology patients.

The study of role of stress in children with behavior disorders and orofacial lesions.

AIM: (1) To study the behavior disorders in children between 5 to 15 years. (2) To study the role of stress in causing behavior disorders. (3) To interpret the orofacial findings in children with behavior disorders. (4) Correlate the orofacial findings with behavior disorder. MATERIALS AND METHODS: Ninty children with behavior problems between age of 5 to 15 years along with their parents who visited the Department of Child-Guidance Clinic, BYL Nair Charitable Hospital, Mumbai. Intraoral examinations were conducted. Behavioral disorders and factors predisposing to those disorders were recorded. RESULTS: Behavior disorders with orofacial lesions was more common in age group of 8 to 10 years. The children were continuously under stress, which manifested in the form of various orofacial disorders or oral lesions. Most common orofacial condition was bruxism. CONCLUSION: Awareness of behavior disorders in dental treatment should guide the pediatric dentist to seek child psychiatric consultation for behavioral disorders to enable early evaluation of the underlying disorder. CLINICAL SIGNIFICANCE: The present study suggested that orofacial and behavior characteristics can serve as markers to diagnose children with behavioral disorders. It also serves as a guide to dental clinicians to refer such children to psychiatrists or pediatricians for early identification, prevention and treatment.

Immunoglobulin A deficiency and oral health status: a case-control study.

INTRODUCTION: Immunoglobulin A (IgA) is important for mucosal health. Selective IgA deficiency (IgAD) is the most common primary immunodeficiency but its effect on oral health is unclear. The aim of this study was to investigate dental, periodontal and oral mucosal health in IgAD individuals. MATERIAL AND METHODS: In total, 32 adult IgAD subjects were compared with 63 randomly selected individuals. Participants answered questionnaires regarding general and oral health and underwent oral examination, including examination using the periodontal screening and recording (PSR) system and dental examination using the DMF system. RESULTS: The IgAD individuals had significantly more often undergone tonsillectomy (44%versus 24%, p=0.046) and adenoidectomy (31%versus 8%, p=0.003) compared with the controls. Furthermore, the IgAD subjects reported having pharyngitis, stomatitis and herpes labialis significantly more often. There was no significant difference in periodontal health (mean PSR index; 1.87 versus 1.77) or dental health (mean DMFS; 51.3 versus 53.7) between the two cohorts. A positive correlation between Helicobacter pylori infection and severity of periodontitis was found (p=0.036). CONCLUSION: IgAD predisposes to oral mucosal infections but does not influence periodontal or dental health. This is the first controlled study to include detailed clinical history and investigations, together with full oral and dental examination, in adults with IgAD.

Prevention of ulcerative lesions by episodic treatment of recurrent herpes labialis: A literature review.

There are substantial difficulties involved in carrying out clinical studies of recurrent herpes labialis, since the disease has a rapid onset, short-lasting viral shedding period and is rapidly self-healing. The aim of this paper was to critically assess published reports of episodic treatment of herpes labialis and to review biological and methodological problems involved in such studies. Limited, but statistically significant, results have been shown with topical antivirals, such as acyclovir and penciclovir, improving healing times by approximately 10%. Orally administrated antivirals, such as valaciclovir and famciclovir, have subsequently found clinical use. However, these two oral medications have different profiles in phase 3 studies. Famciclovir showed additional improvement of efficacy in terms of lesion healing time, but no effect on prevention of ulcerative lesions, while valaciclovir appeared to have similar efficacy to that of acyclovir cream on lesion healing, but some additional efficacy with respect to prevention of ulcerative lesions. A formulation of acyclovir/hydrocortisone showed further improvement in prevention of ulcerative lesions, while retaining efficacy with respect to lesion healing.

Recurrent infections in patients with nickel allergic hypersensitivity.

Nickel (Ni) is the most common contact allergen among the general population in the industrialized world. Ni has been shown to exhibit immunomodulatory, if not immunotoxic, effects in several experiments conducted on humans and on rodents. This study tests the incidence of different infectious diseases in 100 patients with Ni hypersensitivity and compares it to data from 100 healthy volunteers. One hundred subjects with Ni hypersensitivity were enrolled. A group of 100 matched healthy volunteers with negative European standard patch test were enrolled as healthy controls. In patients with Ni hypersensitivity a higher incidence of recurrent herpes labialis (RHL), urinary tract infections (RUTI), genital candidiasis, and upper respiratory tract infections (RURTI) was detected. Fifteen patients with nickel allergic hypersensitivity (NAH) followed a Ni-poor diet. After a one-year diet a net reduction of incidence of RHL was found. Indeed, the number of episodes of RHL per year decreased from 6 +/- 2.75 to 2.4 +/- 1.2. Conversely, among the matched control group with NAH following a normal daily dietary nickel intake the RHL number did not show any statistically significant changes (6.1 +/- 1.7 vs 6 +/- 1.5 ). In conclusion, our study demonstrates a higher incidence of recurrent infections among patients with NAH. A low-Ni diet reduces the number of RHL episodes per year.

Oral herpes simplex virus infection in pregnancy: what are the concerns?

Although epidemiologic data and the potentially serious effects of transmission of genital herpes from mother to infant during birth have been widely reported, published reports on oral herpes disease in pregnancy remain scarce and no clear management guidelines exist. Thus, questions remain about acquisition, transmission and outcome of infection, especially with respect to acute gingivostomatitis in pregnancy. In response to these questions, we summarize previous reports on herpes simplex virus 1 (HSV-1) oral disease in pregnancy and, briefly, present 2 cases of primary gingivostomatitis in the first trimester of pregnancy, resulting in a favourable outcome for both mother and infant. We also point out the most recent data on rare, potentially severe in outcome, but treatable, primary central nervous system HSV-1 infection in later stages of pregnancy. Finally, we emphasize a multidisciplinary approach to oral HSV disease in pregnancy, with dentist participation in the diagnosis and treatment.

The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behçet's disease.

Behçet's disease (BD) is a multisystemic disorder characterized by oral, genital ulcers and involvement of the cutaneous (erythema nodosum, pustular vasculitis), ocular (anterior or posterior uveitis), musculoskeletal, vascular (both arterial and venous vasculitis), gastrointestinal and central nervous (meningoencephalitis) systems. It has an unpredictable clinical spectrum from mild mucocutaneous manifestations to severe ocular, vascular or neurological disability. In this review, the aetiology, clinical presentations and treatment modalities of BD are evaluated in the context of microbial factors within the existing literature. The relationships between microbial agents (streptococcia and herpes simplex virus), microbial antigens [heat shock proteins (HSP), lipoteichoic acid (LTA)] and immune mechanisms such as innate and adaptive responses against microorganisms are discussed.

Herpetic whitlow.

Herpetic whitlow is a painful cutaneous infection that most commonly affects the distal phalanx of the fingers and occasionally the toes. It is caused by herpes simplex virus (HSV) types 1 or 2. Herpetic whitlow has been known mainly for infecting healthcare workers in contact with infected secretions or mucous membranes, but the implementation of universal precautions has resulted in a decrease in the incidence of occupation-related cases. Herpetic whitlow occurs mainly in adults aged 20 to 30 years and children. In children, most cases can be attributed to autoinoculation of HSV-1, while in adolescents and adults, herpetic whitlow tends to be caused by autoinoculation of HSV-2. Herpetic whitlow may have a prodrome of burning, pruritus, and/or tingling of the affected finger or the entire limb, followed by erythema, pain, and vesicle formation.

Longitudinal evaluation of herpes simplex virus DNA load during episodes of herpes labialis.

BACKGROUND: Few studies have performed sequential evaluation of the herpes simplex virus (HSV) load using quantitative PCR during episodes of herpes labialis. OBJECTIVE: To determine HSV viral load kinetics during recurrences of herpes labialis. STUDY DESIGN: Twenty-two subjects were monitored by daily swabs during recurrences of herpes labialis. A real-time PCR detecting both HSV-1 and HSV-2 was used to quantify the viral load. RESULTS: Median duration of HSV-1 shedding was 60 h and 48 h by PCR and culture, respectively. No HSV-2 DNA was detected in that study. Peak viral DNA load (123.6 copies/cell) occurred at 48 h with no virus detected beyond 96 h of onset of symptoms. CONCLUSIONS: These viral load kinetics data could be used as surrogate markers of antiviral activity in future clinical trials.