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We present the case of a 49-year-old woman with a seronegative rheumatoid arthritis who developed pustular psoriasis whilst on etanercept and subsequently developed disseminated herpes simplex on infliximab.
Our patient presented with an inflammatory arthritis which failed to respond to both methotrexate and leflunomide, and sulphasalazine treatmen...
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Objective
Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting.
Methods
We used data for...
Citations
... Consistent with this study's findings, several research have identified a link between Herpesviruses, inflammation and RA [22,[38][39][40]. Some evidence connects Alpha herpesviruses including Herpes zoster and Herpes simplex viruses to RA [41,42], Herpesviruses have been detected in RA patients' blood and synovial fluid [40]. It was observed that RA patients receiving glucocorticoids and targeted synthetic DMARDs (Disease-modifying antirheumatic drugs) are at higher risk of Herpes zoster virus [42]. ...
Background
Despite evidence linking viruses and oral microbiome to rheumatoid arthritis (RA), limited whole genome sequencing research has been conducted on the oral virome (a viral component of the microbiome) of untreated RA patients. This pilot research seeks to address this knowledge gap by comparing the oral virome of untreated rheumatoid arthritis patients (RAs) and healthy individuals (HCs).
Method
Whole genome DNA sequence of saliva samples from 45 participants including 21 RAs and 24 age and gender matched HCs was obtained from the BioProject: PRJEB6997. Metaphlan3 pipeline and LEfSe analysis were used for the viral signature detection. Wilcoxon pairwise test and ROC analysis were used to validate and predict signatures.
Results
RA exhibits higher alpha diversity compared to HCs. Callitrichine gammaherpesvirus 3, Human gammaherpesvirus 4 (EBV), Murid betaherpesvirus 8, and Suid alphaherpesvirus 1 were enriched in RAs, while Aotine betaherpesvirus 1 from the Cytomegalovirus genus was enriched in HCs. In addition, Saccharomyces cerevisiae killer virus M1 (ScV-M1) was found to be enriched in RAs, whereas bacteriophage Hk97virus (Siphoviridae) and Cd119virus (Myoviridae) were enriched in HCs.
Conclusion
This study identifies significant DNA oral viral signatures at species level as potential biomarkers for the early detection and diagnosis of rheumatoid arthritis.
... [2]. Previous reports have shown an increased herpes zoster virus (HZV) risk in RA patients associated with the use of glucocorticoids and targeted synthetic DMARDs [3,4]. Less is known about herpes simplex in RA and the effect of immunomodulation. ...
... The equally frequently reported adverse reactions occurring after biological drug administration include occurrence or intensification of contagious diseases and opportunistic infections [13]. Bergler-Czop et al. [15] describe occurrence of zoster during adalimumab therapy whereas Justice et al. [16] present disseminated cutaneous herpes simplex virus after infliximab treatment. ...
Psoriasis is one of the most common, chronic skin diseases of as yet unexplained etiopathogenesis. In the recent years it has been proven that an immunological factor plays an important role in the dermatosis onset. This has led to introduction of biological drugs to the disease treatment regimen, which include, inter alia, adalimumab and ustekinumab. New therapy has become an alternative for patients with psoriasis resistant to standard treatment methods as well as an alternative form of treatment in case of occurrence of severe adverse drug reactions after administration of standard treatment. Despite good treatment results the administration of these drugs is associated with the occurrence of adverse reactions. This article presents cases of 4 patients who have been administered biological treatment and in whom there have been observed, inter alia, the occurrence of hypersensitivity reactions in the form of acute urticaria as well as skin lesions of erythema multiforme nature or positive antinuclear antibodies titre. The symptoms experienced by the presented patients posed no direct threat to life and the benefits of the drugs' administration had a significant therapeutic importance.
... 28 Entre las principales manifestaciones clínicas reportadas tras el uso de infliximab en pacientes con artritis reumatoide se encuentran diseminación cutánea, herpes labial y encefalitis. 29 Además, se han reportado casos aislados de encefalitis causada por VHS-1 resistente a aciclovir tras el uso de adalimumab. 30 En la actualidad, no está indicado el screening para VHS previo al inicio de terapia con anti-TNF-α, por lo que la administración pro-filáctica de aciclovir deberá considerarse e individualizarse en pacientes con alto riesgo de recaídas. ...
... A pathway analysis was performed on all putative disease-associated target genes using the Kyoto Encyclopedia of Genes and Genomes (KEGG) [53][54][55], a curated database of molecular pathways and disease signatures (see the "KEGG pathway analysis" section). The top 5 resulting KEGG pathways (Table 1) have been previously (directly or indirectly) associated with rheumatoid arthritis [56][57][58][59][60]. A complete list of all predicted gene-enhancer pairs associated with at least 1 of the top 5 KEGG pathways can be found in Additional file 1: Table S7. ...
We present the software Condition-specific Regulatory Units Prediction (CRUP) to infer from epigenetic marks a list of regulatory units consisting of dynamically changing enhancers with their target genes. The workflow consists of a novel pre-trained enhancer predictor that can be reliably applied across cell types and species, solely based on histone modification ChIP-seq data. Enhancers are subsequently assigned to different conditions and correlated with gene expression to derive regulatory units. We thoroughly test and then apply CRUP to a rheumatoid arthritis model, identifying enhancer-gene pairs comprising known disease genes as well as new candidate genes.
... [5] RA patients are often on immunosuppressives which make them further susceptible to develop secondary viral, bacterial, or fungal infections. [20] Ziemer et al. observed such infections in 7.5% of their patients. [6] In our study herpes infection seen in 1%. ...
... [8] Justice et al. reported a case of widespread cutaneous herpes simplex virus type 1 infection following treatment with infliximab. [21] Pustular psoriasis [20] and MTX-related lymphoproliferative disorder with extensive vascular involvement have also been described recently. [22] Raynaud's phenomenon (RP) is an exaggerated response to cold temperature or stress. ...
... 16 Serious infections occur at an estimated rate of 6.7 events per 100 patient years in Crohn's disease patients receiving treatment with TNF-α inhibitors. 17 The first case of disseminated (cutaneous) HSV-1 infection following treatment with TNF-α inhibitor (infliximab) 18 However, there are limited data on the effect of TNF-α inhibitors on the incidence of tissue-invasive HSV infections. 8 To the best of our knowledge, to date, there are only two reported cases of IBD treated by TNF-α inhibitors (infliximab and adalimumab) with subsequent development of HSV hepatitis. ...
Herpes simplex virus (HSV) hepatitis is an uncommon cause of fulminant hepatic failure, seen mostly in immunocompromised patients. Conventional treatment modalities for inflammatory bowel disease (IBD), such as steroids and azathioprine, have been known to cause HSV hepatitis. However, the reported incidence of HSV hepatitis in IBD patients undergoing tumor necrosis factor (TNF)-α inhibitor therapy is very rare. In this case report, we describe a rare case of fulminant HSV hepatitis that developed in a patient with Crohn’s disease after treatment with the TNF-α inhibitor, adalimumab.
... Herpes simplex virus (HSV) is also a concern in patients with some biologic targeted therapies. Different cases in the literature describe HSV encephalitis and disseminated cutaneous infections with the use of TNFα-targeted agents [69][70][71], and in rituximab regimens for lymphoma treatment, HSV infection was present in 1.6%. In addition, bortezomib-based therapies for multiple myeloma show an increased risk of HSV infection, as with VZV, and prophylaxis is also recommended [62]. ...
Introduction: The development of biologic therapies for treating patients with rheumatic, hematologic, or oncological diseases has increased in the last few years, spreading their use in clinical practice.
Areas covered: Clinical experience has evidenced substantial risks for some viral infections and/or reactivations such as viral hepatitis, herpetic infections and other viruses, as a consequence of specific immune pathway blockages. Biological therapies produce a variable risk of reactivation of viral infections, which is particularly uncertain in the case of the most recently introduced agents. Here we make an extensive review of the viral infections associated with the use of biological drugs and provide a series of recommendations for its prevention and management.
Expert commentary: To prevent these infections/reactivations, the practitioner must be aware of the infection-risk profile, performing accurate screening during and after the use of any biologic agent. In some instances, expert recommendations are made for some therapies, while in other scenarios recommendations have not yet been defined making experimental and clinical research an essential approach to elucidate multiple issues yet not resolved in this field.
... [5] RA patients are often on immunosuppressives which make them further susceptible to develop secondary viral, bacterial, or fungal infections. [20] Ziemer et al. observed such infections in 7.5% of their patients. [6] A much higher percentage (34.2%) of patients of the current series had cutaneous infections. ...
... [8] Justice et al. reported a case of widespread cutaneous herpes simplex virus type 1 infection following treatment with infliximab. [22] Pustular psoriasis [20] and MTX-related lymphoproliferative disorder with extensive vascular involvement have also been described recently. [23] The other cutaneous manifestations of RA may include skin atrophy, transparent skin, generalized hyperpigmentation, hyperhidrosis of the palms, erythema nodosum, alopecia, vitiligo, contact dermatitis, urticaria, tylosis, clavus, ingrown nail, among others. ...
Background: Cutaneous manifestations are fairly common in rheumatoid arthritis (RA) and
they can help in early diagnosis, prompt treatment, and hence reduced morbidity from the
disease. Aims: The objective of the present study was to find out the different patterns of
dermatoses in a group of patients with RA from Eastern India. Methodology: Consecutive
patients fulfilling the American Rheumatism Association 1987 revised criteria for the
classification of RA and who had different dermatoses were included in this cross‑sectional
study done over a period of 8 years in a tertiary care hospital in Eastern India. Thorough
clinical examination and appropriate laboratory investigations were performed as needed.
Data were recorded in a predesigned schedule, and appropriate statistical analysis was done.
Results: We studied 111 evaluable patients with an age range of 19–71 years and a female
to male ratio of 7:1. The mean disease duration of RA was 6.5 years. Cutaneous infections
as a group was the most common mucocutaneous manifestation (34.2%) followed by xerosis
including ichthyotic skin changes (27%), pigmented purpuric dermatoses (14.4%), leg
ulcer (9.9%), periungual telangiectasia (9.9%), rheumatoid nodules (RNs) (8.1%), purpura
and ecchymoses (7.2%), small vessel vasculitis in (7.2%), corn and callosities (6.3%), palmar
erythema (4.5%), and neutrophilic dermatosis (4.5%). Raynaud’s phenomenon was found in
3.6% patients and panniculitis in (3.6%) patients. Rheumatoid factor (RF) and anti‑cyclic
citrullinated peptides antibody were positive in 74.8% and 88.3% patients, respectively.
No statistically significant difference of incidence of leg ulcer, small vessel vasculitis, RN,
or Raynaud’s phenomenon could be noted between RF positive and negative groups.
Limitations: Being an institution‑based study, the study findings may not reflect the true
situation in the community which remained a limitation of this study. Conclusion: While
some of the features of this study were analogous to Western data, other features showed
discordance which may be due to ethnic variations among the patients with RA.
... 8,9,10,11,12,13 There are also some reported cases of cutaneous herpes simplex virus (HSV) infection following treatment with infliximab. 14, 15 We are not aware of any published reports of ocular HSV infections associated with use of TNF inhibitors. ...
A 51-year-old man was diagnosed with Behçet’s disease in 2001. The patient was resistant to all immunosuppressive therapies. After
6 months of infliximab therapy, he presented to our clinic with pain and blurred vision in his right eye. The visual acuity was 20/200
and the intraocular pressure was 35 mmHg in the right eye. Biomicroscopic examination revealed corneal dendritic ulcers and 2+ cells
in the anterior chamber in the right eye. The herpetic keratouveitis attack was controlled with antiviral therapy but the patient needed
another glaucoma surgery. Trabeculectomy with mitomycin C was performed about halfway through an eight-week interval between
two doses of infliximab.
