{"paper_id":"33faeeb6-700d-496b-984b-e1492aba6ed9","body_text":"Severe HSV1 pneumonia and EBV enteritidis in a patient with Felty syndrome and ulcerative colitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Severe HSV1 pneumonia and EBV enteritidis in a patient with Felty syndrome and ulcerative colitis Jianjun He, Da Liu, ShaLi Jiang, Sai Wang, Yongfeng Zhu, Yafei Yin, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4227348/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Felty syndrome (FS), as a rare syndrome, primarily presents as splenomegaly and neutropenia in the context of rheumatoid arthritis (RA).although Inflammatory bowel disease and rheumatoid arthritis are both autoimmune diseases, they only appear together in rare cases.Herpesviruses can be activated in this pathological process, thereby precipitating associated infections, including severe herpes simplex virus type 1(HSV1) pneumonia, and Epstein-Barr virus (EBV) enteritidis in our case. Case presentation: Here, we report a case illustrating the rapid deterioration of FS following the discontinuation of prednisone andmethotrexate. During the course, this patient exhibited fever, diarrhea, cold sores, and finally be dignosed severe HSV1 pneumonia, cheilitis, EBV enteritidis and ulcerative colitis. Conclusions: In patients with rheumatoid arthritis, sudden cessation of anti rheumatic drugs may induce Felty syndrome, which in turn can induce the activation of herpesvirus in the body, leading to a series of herpesvirus related infections, such as ,cheilitis, pneumonia and enteritis. Early intravenous use of sufficient antiviral drugs and timely initiation of antirheumatic drugs may be a more appropriate solution. HSV-1 pneumonia Felty syndrome EBV enteritidis ulcerative colitis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction HSV-1 pneumonia is an uncommon but severe disease, with an incidence rate of approximately 0.5% [ 1 ] and a mortality rate that can reach up to 60% [ 2 ] . It arises from the direct spread of viruses in the upper and lower respiratory tract, or from reproductive organs and oral lesions most likely through bloodstream. Its clinical manifestations include cough, shortness of breath, fever, hypoxemia, reduced white blood cell count, which may be accompanied by HSV damage to the skin and mucosa, but with no specificity. Epstein-Barr virus associated enteritis is unusual ,with which is easily misdiagnosed as inflammatory bowel disease(IBD) and has the possibility of transitioning to precancerous lesions or tumors. The prognosis of most patients is poor and should be taken seriously by clinical physicians. However, multicenter studies in China have suggested that compared to patients with IBD, those with Epstein-Barr virus associated enteritis more commonly present with intermittent fever, hepatosplenomegaly, and lymphadenopathy. C-reactive protein and serum EB virus DNA load are significantly elevated in these patients [ 3 ] . FS, known as \"super rheumatoid arthritis\", is a relatively rare complication in rheumatoid arthritis (RA) patients, with an incidence rate of approximately 1–3%, primarily characterized by splenomegaly and neutropenia [ 4 ] . 1/3 of patients may have typical features of Felty's syndrome such as neutropenia and rheumatoid arthritis, but without splenomegaly. About 60% of patients with this disease have secondary infections, mostly on the skin or in respiratory tract. The pathogenic bacteria are mostly common Staphylococcus, Streptococcus, and Gram-negative bacterium. Infection may be related to a decrease in granulocytes. Here we report a case illustrating the rapid deterioration of FS following the discontinuation of prednisone and methotrexate. During the course of treatment, the patient suffered from ulcerative colitis(UC) and experienced activation of herpesviruses, including HSV1 pneumonia, cheilitis, EBV enteritidis. Ultimately, through an extended period of antiviral and immunomodulatory therapy, the patient's condition improved. Case presentation A 65-year-old male patient was admitted to our hospital on December 30, 2023, with complaints of \"Bilateral hand joint pain for 8 months, diarrhea for 1 months, and fever for 3 days.\" 8 months prior to admission, the patient experienced joint pain in both hands accompanied by morning stiffness lasting more than 1 hour, which progressively worsened. At a local hospital, the patient's Rheumatoid Factor (RF) was measured at 159.20 IU/ml, and anti-citrullinated peptide antibody (ACPA) was 287.40 U/ml. Color Doppler imaging of the wrist indicated synovitis thickening in both wrists, leading to a diagnosis of rheumatoid arthritis. Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scores of 36 and 37, respectively, suggested high disease activity, prompting initiation of prednisone and methotrexate antirheumatic therapy. One month prior to admission, the patient had diarrhea, with mucopurulent bloody stools for about 7–8 times a day, accompanied by poor appetite and fatigue. The patient stopped methotrexate and was hospitalized in another facility's rheumatology department, where routine blood tests revealed pancytopenia with white blood cell (WBC) count of 1.96×10 9 /L, hemoglobin (Hb) of 92g/L, platelet(PLT) count 94×10 9 /L and absolute neutrophil count of 0.65×10 9 /L. Due to concurrent diarrhea, prednisone was discontinued, and anti-infection treatment with meropenem was initiated without improvement. Three days before admission, the patient developed fever and mildly dry cough. He underwent chest and abdominal CT scan, revealing multiple lung abnormalities, mediastinal lymphadenopathy, and diffuse colon wall thickening. Consequently, the patient was transferred to the respiratory department of our hospital for further treatment. Throughout the illness, the patient exhibited poor appetite, mental state and extreme emaciation. The patient's history includes a 30 pack-year smoking habit. Physical examination revealed a high temperature about 40.0 degree centigrade, polypnea with breathing rate of 26 times per minute and finger pulse oxygen saturation of 92%. Multiple ruptures and blisters on the upper and lower lips, with some forming irregular erosion surfaces of varying sizes, surrounded by red halos and black scabs could be observed (Fig. 1 ). Bilateral enlarged supraclavicular fossa can be palpated as \"soybean sized\", regular morphology, tenderness, and moderate mobility. Breathing sounds were clear in both lungs and no rhonchus or rale could be heard. There was a mild tenderness around the navel with an active bowel sounds about 7–8 beats per minute. Joints examination revealed arthroncus and deformities in both interphalangeal, metacarpophalangeal and wrist joints (Fig. 2 ). On admission, the results of blood tests were as follows: WBC 1.96×10 9 /L, Hb 76g/L, PLT 52×10 9 /L and absolute neutrophil count of 0.25×10 9 /L,C-reactive protein levels 99.60mg/L, erythrocyte sedimentation rate 112mm/h, procalcitonin 1.83ng/ml, IL-6 712.50pg/ml, ferritin 1520ng/ml, serum EB viral deoxyribonucleic acid 1.35×10 5 copies/ml, Herpes simplex virus type-1 IgG antibody 867.61AU/ml. While other biochemical parameters, including hepatic and renal functions, blood glucose, serum lipid, electrolyte, coagulation function and tuberculosis interferon gamma release assay were unremarkable. Sputum pathogens smear and culture, including bacteria, tuberculosis, and fungi were negative. Sputum targeted pathogen second-generation sequencing(tNGS) revealed human herpesvirus type 1(sequence number: 121402). Bronchoalveolar lavage fluid tNGS also revealed human herpesvirus type 1(sequence number: 25588). Ultrasonographic evaluations unveiled enlarged bilateral supraclavicular lymph nodes (Fig. 3 ) and synovial hyperplasia in the wrists (Fig. 4 ). Radiological investigations delineated diffuse pulmonary anomalies, especially in both upper lung (Fig. 5 a), along with colonic wall thickening (Fig. 6 a). Bronchoscope revealed mild airway mucosa hyperemia (Fig. 7 ). Colonoscopy revealed chronic active inflammation and mucosal erosion (Fig. 8 ), while in situ hybridization unveiled EBV-encoded RNA in lymphocytes (Fig. 9). Bone marrow scrutiny delineated stable hyperplasia, diminished red and megakaryocyte lines, and anomalous granule morphology. On admission, considering the patient had long-standing rheumatoid arthritis prescribed with prednisone and methotrexate, Chest CT imaging exhibited polymorphic lesions of both upper lungs, blood test showed granulocytopenia, tuberculologist prompted suspicion of secondary pulmonary tuberculosis and bacterial pneumonia. However, evidence towards pulmonary tuberculosis was absent and broad-spectrum anti-bacterial therapy failed. After discontinuation of immunosuppressive medicine, the patient's condition still deteriorated rapidly, with progressive pulmonary involvement and persistent systemic symptoms. Through further examination and discussion, Pulmonary physicians diagnosed HSV1 pneumonia and Antiviral therapy with adenosine and acyclovir was initiated, yet the patient's fever persisted and pulmonary and labial lesions progressed after a week. We conducted multidisciplinary consultations to guide decisions regarding diagnostic tests and treatment. Gastroenterologist diagnosed UC complicated with EBV related enteritidis considering intestinal manifestations and pathological results and advised anti-EBV therapy with Ganciclovir and change from mesalazine tablets to mesalazine granule was essential. Dermatologists recommended recombinant human interferon α-2b gel for external use combined with systemic antiviral therapy is necessary for recurrent herpes labialis. Hematologist provided recommendations for the differential diagnosis of pancytopenia. The diagnosis of hemophagocytic syndrome, leukemia, lymphoma lacks sufficient evidence, but we should attach importance to accompanied EBV activation. Intravenous Ganciclovir and immunoglobulin could be a better choice. Besides, granulocyte colony-stimulating factor(G-CSF) could be administered. Rheumatologist identified Felty syndrome as the cause of pancytopenia and advised anti-inflammatory and immunoregulatory therapy with methylprednisolone and immunoglobulin, but methotrexate must be prescribed after pneumonia improved. Pharmaceutical experts recommended antiviral therapy should be extended to two weeks or more depending on the patient’s recovery condition. During the period, physician should pay close attention to adverse drug reactions, such as neurotoxicity and renal dysfunction. After multidisciplinary discussion, we discontinued acyclovir and initiated intravenous ganciclovir 0.3g q12h for antiviral therapy, recombinant human interferon α-2b gel for external use, alongside methylprednisolone 40mg qd ,immunoglobulin 10g qd, mesalazine granule 1.0g qid and G-CSF 200ug tiw. Within 2 weeks, the oral cold sores healed visibly (Fig. 1 c), while lung lesions showed significant improvement (Fig. 5 b), leading to improvement of respiratory failure and the diarrhea vanished with intestinal CT revealing subsided intestinal edema (Fig. 6 b). But the patient still complained fever, joint pain of hands and refractory granulocytopenia. methotrexate (10mg qw) for anti-rheumatic purposes was added, combined with G-CSF at a dose of 200ug biw to elevate leukocyte count. Subsequent one-month follow-up revealed resolution of fever, alleviation of joint pain, and normalization of repeated blood routine examination after G-CSF stopped one month later. Discussion It is a complex case of multi organ viral activation, as HSV1 pneumonia, cheilitis and EBV enteritidis in the context of RA and UC. Following discontinuation of prednisone and methotrexate due to persistent diarrhea, the patient experienced uncontrolled rheumatic activity and refractory panhemopenia. Despite initial acyclovir being ineffective, subsequent adjustment to ganciclovir and immunoglobulin proved beneficial. Continuation of methylprednisolone, methotrexate, and mesalazine gradually alleviated symptoms associated with FS and UC. Pancytopenia was observed to improve one month later after initiating G-CSF treatment. RA combined with UC is not common in clinical practice. It was reported that the occurrence rate of RA combined with IBD is around 5–10% [ 5 ] . The etiology of UC remains elusive, likely stemming from alterations in gut microbiota, genetic predisposition, and environmental factors. The IL-23/IL-17 axis is a common inflammatory pathway, playing a crucial role in the pathological process by inducing the production of inflammatory cytokines and tissue inflammation in both RA and UC, with IL-23 being a key cytokine [ 6 ] .Short-chain fatty acids, particularly butyrate, produced by gut bacteria, are crucial for intestinal health, known to inhibit pro-inflammatory cytokine formation, enhance epithelial cell integrity, and bolster the gut barrier by fortifying tight junctions [ 7 ] . Studies have shown that fecal microbiota transplantation can induce remission in UC patients, attributed to increased microbial diversity, including butyrate-producing species like Eubacterium hallii [ 8 ] . Conversely, a deficiency in butyrate-producing species and reduced microbial diversity have been observed in RA patients, with intestinal butyrate metabolites implicated in RA autoantibody production and bone erosion [ 9 ] . This contradiction in the roles of short-chain fatty acids may partly explain the rare co-occurrence of UC and RA.Genetic factors also contribute to IBD, with up to 12% of affected individuals having a family history [ 10 ] . Among the numerous risk genes associated with IBD, NOD2 is extensively studied. NOD2 encodes a receptor in intestinal epithelial cells and lymphocytes, which recognizes bacterial cell wall dipeptides and triggers pro-inflammatory cytokine production [ 11 ] . Down-regulation of NOD2 gene expression has been linked to reduced inflammation in RA synovial fibroblasts, suggesting a pro-inflammatory role of NOD2 in RA [ 12 ] . Moreover, genome-wide association studies have identified shared gene loci between IBD and RA, as PTPN22 , FCGR2A , IL2/IL21 , that play important roles in the activation and differentiation of immune cells, as well as cytokine signaling, and jointly participate in the occurrence of IBD and RA [ 13 ] . Environmental factors also influence the onset of IBD, with smoking, place of residence, and air pollution being significant contributors. Smoking, in particular, is closely associated with RA pathogenesis, as it induces the expression of enzymes that generate immune-triggering neoantigens [ 14 ] . We performed whole exome sequencing on the patient but did not detect any related genetic variations. Despite residing in rural areas, the patient's prolonged heavy smoking history might have contributed to the development of RA combined with UC. During RA treatment, the patient exhibited diarrhea, elevated serum EBV nucleic acid levels, and systemic lymph node enlargement, prompting consideration of EBV activation. Notably, intestinal pathology revealed strong positive EBER in infiltrated lymphocytes, and active anti-EBV treatment improved symptoms, indicating EBV's potential role in the pathogenesis of UC. Although the exact mechanism remains elusive, studies suggest that EBV infection may induce DNA damage and dysregulate autophagy in colon cells via ERK1/2 signaling pathway. Epigenetic modulation of these processes, such as with 5-Azacytidine, can activate ERK1/2 pathway and mitigate inflammation, suggesting a therapeutic potential for anti-EBV therapy in UC [ 15 ] . Belonging to the Herpesviridae family, comprising structurally similar, enveloped DNA viruses, more than 100 viruses have been documented, with eight types associated with human infection, categorized into three subfamilies [ 16 ] . While approximately 66% of the global population carries HSV-1, most individuals remain asymptomatic after primary infection, with the virus entering a latent state in ganglia, particularly the trigeminal ganglia. Reactivation of HSV1 can manifest as recurrent perioral or oral lesions (\"cold sores\") and skin/mucosal lesions when the immune system is compromised [ 17 ] . Studies have linked lip herpes occurrence in some individuals during COVID-19 infection to latent herpes simplex reactivation [ 18 ] . In this case, concurrent HSV1 pneumonia and cheilitis, coupled with EBV enteritis, involved in the pathogenesis of FS and UC. Further research is warranted to investigate whether EBV can also trigger latent herpes simplex reactivation. HSV1 pneumonia is an uncommon occurrence in respiratory virus infections, with a mere 0.5% incidence in lower respiratory tract infections, usually occurs in specific individuals such as HIV infection, malignant tumors, organ transplantation, or immune dysfunction. Clinical manifestations are atypical, including cough, shortness of breath, fever, hypoxia, may be accompanied by skin and mucosal HSV damage. Chest CT findings present the following characteristics: central lobular nodule with surrounding patchy ground glass lesions (called halo sign), grid shadows, thickening of interlobular septa, diffuse ground glass lesions and pleural effusion. The diagnosis of HSV1 pneumonia contain clinical manifestation, changes of chest CT imaging, and histological evidence or virus isolation from the lower respiratory tract. Regrettably, HSV1 pneumonia wasn’t diagnosed initially for this patient, although HSV1 was detected in the sputum specimen. However, despite antibacterial treatment, the lack of response prompted a reevaluation via bronchoscopy, revealing the persistence of HSV1 in alveolar lavage fluid. Nucleoside antiviral drugs such as acyclovir and ganciclovir are commonly used for HSV1 infection, with the course of treatment is about 9 days in immunocompetent patients and about 17 days in immunocompromised patients [ 19 ] . However, in our case, after a week of acyclovir treatment, the patient’s respiratory failure persisted, and lung lesion enlarged. Perhaps lung injury not only occurred from direct viral damage, but also from immunological damage caused by internal inflammatory storms caused by uncontrolled FS, UC and EBV activation. The changes in the composition and function of the gut microbiota affect the respiratory system through mucosal immune system, and the disruption of the respiratory microbiota can also affect the digestive tract through immune regulation. This interaction between the gut and lungs is called the lung-gut axis. In 2018, an article in Science reported that natural lymphocytes involved in pathological processes such as homeostasis, asthma, and chronic obstructive pulmonary disease (COPD) may migrate from the intestine to the lungs and participate in lung immune responses [ 20 ] . Inflammatory type 2 natural lymphocytes enter the bloodstream through the lymphatic system and function in the lungs. There is current research focusing on the role of the gut-lung axis in various diseases, such as using the modulation of gut microbiota as a novel therapeutic target for COPD [ 21 ] . This all suggests that when lung diseases are combined with intestinal manifestations, attention should be paid to the treatment of intestinal diseases. Following multidisciplinary team discussions, significant improvement occurred after 14 days of intravenous ganciclovir combined with immunoglobulin therapy. During follow-up, HSV1 pneumonia did not recur, and body temperature normalized. Clinical studies have shown HSV1 mortality rates is up to 63% in severe respiratory infection patients [ 22 ] , with those having normal immune function, exhibiting more severe clinical manifestations and higher mortality [ 18 ] . If patients with RA experiencing progressive pancytopenia, particularly persistent neutropenia, clinical physicians should be vigilant for FS even in the absence of splenomegaly, and caution should be exercised when discontinuing antirheumatic drugs. Abrupt cessation of methotrexate has been reported to exacerbate FS, with symptoms gradually improving upon methotrexate re-prescribed leading to a gradual increase in neutrophil counts [ 23 ] . The exact pathogenesis of neutropenia in FS remains unclear but may involve an imbalance between neutrophilic production and clearance. Myelodysplasia, primarily granulocyte maturation disorder, leading to reduced neutrophil production [ 24 ] , and increased autoantibodies in circulation, such as histone H3 antibodies and neutrophil extracellular chromatin traps (NETs) autoantibodies, contribute to enhanced neutrophil clearance [ 25 ] . Corticosteroids, methotrexate, and recombinant human colony-stimulating factor are considered the main therapeutic drugs [ 26 ] , while methotrexate is considered the most effective and well tolerated choice among antirheumatic drugs for improving RA symptoms and neutropenia. Therefore, it is recommended as the first-line treatment for such patients. A study by the Peking Union Medical College Hospital in China reported 17 cases of FS collected over the past 10 years. Successful treatment outcame in most cases with methylprednisolone (30-60mg Qd) and methotrexate (5-15mg qw), while splenectomy was considered for cases with accompanying splenomegaly and poor drug treatment response [ 27 ] . In approximately 80% of cases, neutrophil counts can continue to normalize after splenectomy for more than 6 months. If neutrophil counts could not be elevated by methotrexate, rituximab may be considered, with nearly two-thirds of cases showing normalization after the first course of rituximab treatment, as indicated by systematic review of case reports [ 28 ] . Conclusion We reported an uncommon case of HSV1 pneumonia accompanied by EBV enteritis. Considering the patient developed a multi system including lips, lung, intestinal tract, we further discovered the underlying immune disorders of FS and UC, that probably induced tissue damage through enlarged inflammatory imbalance as our initial antiviral treatment is unsatisfactory. What role does the virus play exactly in the pathogenesis of inflammatory diseases? It may be the pathogenesis, comorbidities, or clinical outcomes, and function diversely. But still now, these researches are insufficient and it deserves more attentions in the future. Abbreviations ACPA: anti-citrullinated peptide antibody; COPD: chronic obstructive pulmonary disease; CDAI: clinical disease activity index; EBV: epstein-barr virus; FS: felty syndrome; G-CSF: granulocyte colony-stimulating factor; HSV1: herpes simplex virus type 1; Hb: hemoglobin; NETs: neutrophil extracellular chromatin traps; PLT: platelet; RA: rheumatoid arthritis; SDAI: simplified disease activity index; tNGS: targeted pathogen second-generation sequencing; UC: ulcerative colitis; WBC: white blood cell. Declarations Acknowledgements Not applicable. Authors ’ contributions Guarantors of integrity of entire study, Liu Da; study concepts/study design or data acquisition or data analysis/interpretation, Jianjun He, Liu Da; manuscript drafting or manuscript revision for important intellectual content, Jianjun He,Liu Da; Contribution of diagnosis and treatment opinions, Da Liu, Shali Jiang, Sai Wang, Yongfeng Zhu, Yafei Yin, Jingjiang Yao; agreement to ensure any questions related to the work are appropriately. Funding This work was supported by the Youth program of the Hunan Provincial Natural Science Foundation of China (2021JJ40622), the National Natural Science Foundation of China (82300042), Changsha Natural Science Foundation of China (kq2007081) and Clinical Medical Research 4310 Project of University of South China (20214310NHYPY04). Availability of data and materials Not applicable. Ethics approval and consent to participate The case report was approved and supervised by The Afffliated Changsha Central Hospital, Hengyang Medical School, University of South China (committee’s reference number：KY-2024-059-02) Consent for publication Informed consent was obtained from the patient. Competing interests The authors declare that they have no competing interest. References Jellinge M E, Hansen F, Coia J E, et al. Herpes simplex virus type 1 pneumonia—a review[J]. Journal of Intensive Care Medicine, 2021, 36(12): 1398-1402. [1]Simoons-Smit A M, Kraan E M, Beishuizen A, et al. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: real pathogen or innocent bystander?[J]. Clinical microbiology and infection, 2006, 12(11): 1050-1059. Liu R, Wang M, Zhang L, et al. The clinicopathologic features of chronic active Epstein-Barr virus infective enteritis[J]. Modern Pathology, 2019, 32(3): 387-395. Pezhouh M K, Miller J A, Sharma R, et al. 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Arthritis & Rheumatism, 2002, 46(9): 2384-2391. Rashba E J, Rowe J M, Packman C H. Treatment of the neutropenia of Felty syndrome[J]. Blood reviews, 1996, 10(3): 177-184. 宋爱凤,张莉,徐东等.费尔蒂综合征17例临床分析[J].中华临床免疫和变态反应杂志,2021,15(05):534-539. Narváez J, Domingo-Domenech E, Gómez-Vaquero C, et al. Biological agents in the management of Felty's syndrome: a systematic review[C]//Seminars in arthritis and rheumatism. WB Saunders, 2012, 41(5): 658-668. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4227348\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":290525807,\"identity\":\"ff1b4185-9d2c-4294-a27e-f9db95f93430\",\"order_by\":0,\"name\":\"Jianjun He\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jianjun\",\"middleName\":\"\",\"lastName\":\"He\",\"suffix\":\"\"},{\"id\":290525809,\"identity\":\"00028c51-3cd7-4ce9-8a07-24cfbb960df2\",\"order_by\":1,\"name\":\"Da Liu\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBACfmbGxgeJfyTk7I83H4AIHSCgRbK9udngY4ONMcOZYwnEaTE4c7xNcmZDWiLDjRwD4rQw3EhsNubdcTiBcUbON8kfNQxyfDcSGD8X4NHBOCOx8THvmcN5zDxvt0nzHGMwlryRwCw9A48WZgmgLTxsh4vZ2HO3STM2MCRuuJHAxsyDRwubRGKbNFBLYg9DzjPJnw0M9QS18PAcBHq/LS1xBkcOmwRvA0OCASEtEuyNzQYfztgYG/AcM7bmOSZhOPPMw2ZpfFrsD7M/fJBQISFnwN788OaPGht5vuPJBz/j04JhKxADA2EUjIJRMApGAWUAABlQUNTU5K/JAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Da\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":290525811,\"identity\":\"86da3f1a-2d5e-418a-8a59-20664e4e9158\",\"order_by\":2,\"name\":\"ShaLi Jiang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"ShaLi\",\"middleName\":\"\",\"lastName\":\"Jiang\",\"suffix\":\"\"},{\"id\":290525813,\"identity\":\"5f9e7996-c3cd-41ee-8f63-b02b26e6ba26\",\"order_by\":3,\"name\":\"Sai Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Sai\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":290525815,\"identity\":\"d24a372c-8809-4e1a-8d90-f290d59f3929\",\"order_by\":4,\"name\":\"Yongfeng Zhu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yongfeng\",\"middleName\":\"\",\"lastName\":\"Zhu\",\"suffix\":\"\"},{\"id\":290525817,\"identity\":\"53ef5121-7652-4645-af57-d2837f6347b7\",\"order_by\":5,\"name\":\"Yafei Yin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yafei\",\"middleName\":\"\",\"lastName\":\"Yin\",\"suffix\":\"\"},{\"id\":290525819,\"identity\":\"3ce118a9-74d4-465d-914d-992111825d8a\",\"order_by\":6,\"name\":\"Jingjiang Yao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Afffliated Changsha Central Hospital, University of South China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jingjiang\",\"middleName\":\"\",\"lastName\":\"Yao\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-04-06 12:14:11\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4227348/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4227348/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":55009720,\"identity\":\"14a9e77c-d087-4266-91f0-d5c66ce7691a\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 19:15:37\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":156100,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eHSV1 related libial lesion. Before antiviral therapy(a); After 1 week of intravenous acyclovir therapy(b); After 2 weeks of intravenous Ganciclovir combined with immunoglobulin therapy(c).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/8556a3800a76ee51ce55fbc4.jpg\"},{\"id\":55007078,\"identity\":\"bb350475-e0dd-4232-9ae8-b6a3ba21b408\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:36\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":198130,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eArthroncus and deformities of the hands\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/1506919be6df7ef97ab0591f.jpg\"},{\"id\":55007079,\"identity\":\"ec4a0f88-4b6a-4a1b-8dd6-e8a64104cd46\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:36\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":155489,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eLymphoglandula ultrasound showed multiple enlarged lymph nodes in both supraclavicular fossas. The largest one is \\u0026nbsp;11mm×7.5mm in left side (a) and 18mm×8.5mm in right side(b).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/fe93a9a3a48abba3c0ddf854.jpg\"},{\"id\":55008702,\"identity\":\"e30a5b57-558f-4ff4-9148-d318f53fda52\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 19:07:36\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":174631,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eWrists ultrasound showed synovial thickening in both sides, 4mm on the right(a) and 4.6mm on the left(b).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/d167eab4ddace9dc9b079fd5.jpg\"},{\"id\":55007076,\"identity\":\"ea6db4b7-abbb-4d7a-90c7-4c635f96ff0a\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:36\",\"extension\":\"jpg\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":483657,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eChest CT imaging before and after therapy. On admission, it showed diffuse patchy and nodular ground-glass opacities (red arrows), interspersed with patchy consolidation (blue arrows), and small nodular opacities (yellow arrows) in both upper lungs(a). After 2 weeks of antiviral and immunoregulatory therapy, it showed the ground-glass opacities in both lungs have decreased(b).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"5.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/06816bc5c9f5ff61218d1269.jpg\"},{\"id\":55007083,\"identity\":\"c5fb9cee-b2c6-4edc-8c20-a68536ab9fd0\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:37\",\"extension\":\"jpg\",\"order_by\":6,\"title\":\"Figure 6\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":509260,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAbdominal CT imaging before and after therapy. On admission, there were significant thickening of the wall, with some colonic haustral pattern shallow or disappearing in entire colon(a). After 2 weeks Mesalazin and antiviral therapy, it showed the edema of the intestinal wall has subsided(b).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"6.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/1f5e9fb61c3a55e3f1f94616.jpg\"},{\"id\":55008703,\"identity\":\"30d4be87-e206-4ef4-a03c-0cc26b530944\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 19:07:37\",\"extension\":\"jpg\",\"order_by\":7,\"title\":\"Figure 7\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":153396,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eBronchoscope revealed airway mucosa hyperemia.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"7.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/f48e07af5a26436f8588d0ae.jpg\"},{\"id\":55007084,\"identity\":\"6016039d-7275-4abe-afc8-10776d3c0808\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:37\",\"extension\":\"jpg\",\"order_by\":8,\"title\":\"Figure 8\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":175108,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eColonoscopy revealed granular changes, erosion, and bleeding in some areas of the mucosa.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"8.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/ec66fa9444855c2800575f7b.jpg\"},{\"id\":55007081,\"identity\":\"6f0addc4-925f-4c62-94cb-7b160c100937\",\"added_by\":\"auto\",\"created_at\":\"2024-04-19 18:59:37\",\"extension\":\"jpg\",\"order_by\":9,\"title\":\"Figure 9\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":299292,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eIntestinal histopathology with HE staining: Extensive mucosal erosion, mixed inflammatory cell infiltration (including abundant lymphocytes, plasma cells, neutrophils, and eosinophils), with crypt distortion and cryptitis, without granulomatous changes (a-b); in situ hybridization for EBER demonstrates lymphocytes positive (c).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"9.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/80a3f1b1df4af9f229fb20ba.jpg\"},{\"id\":57444806,\"identity\":\"85ad25e6-3856-4af3-8b42-491e47ccdc2f\",\"added_by\":\"auto\",\"created_at\":\"2024-05-30 19:07:19\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2646578,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4227348/v1/b476044d-5ad9-42e1-8c93-79b52948e3ff.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Severe HSV1 pneumonia and EBV enteritidis in a patient with Felty syndrome and ulcerative colitis\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eHSV-1 pneumonia is an uncommon but severe disease, with an incidence rate of approximately 0.5%\\u003csup\\u003e[\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]\\u003c/sup\\u003e and a mortality rate that can reach up to 60%\\u003csup\\u003e[\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]\\u003c/sup\\u003e. It arises from the direct spread of viruses in the upper and lower respiratory tract, or from reproductive organs and oral lesions most likely through bloodstream. Its clinical manifestations include cough, shortness of breath, fever, hypoxemia, reduced white blood cell count, which may be accompanied by HSV damage to the skin and mucosa, but with no specificity. Epstein-Barr virus associated enteritis is unusual ,with which is easily misdiagnosed as inflammatory bowel disease(IBD) and has the possibility of transitioning to precancerous lesions or tumors. The prognosis of most patients is poor and should be taken seriously by clinical physicians. However, multicenter studies in China have suggested that compared to patients with IBD, those with Epstein-Barr virus associated enteritis more commonly present with intermittent fever, hepatosplenomegaly, and lymphadenopathy. C-reactive protein and serum EB virus DNA load are significantly elevated in these patients\\u003csup\\u003e[\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e. FS, known as \\\"super rheumatoid arthritis\\\", is a relatively rare complication in rheumatoid arthritis (RA) patients, with an incidence rate of approximately 1\\u0026ndash;3%, primarily characterized by splenomegaly and neutropenia\\u003csup\\u003e[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/sup\\u003e. 1/3 of patients may have typical features of Felty's syndrome such as neutropenia and rheumatoid arthritis, but without splenomegaly. About 60% of patients with this disease have secondary infections, mostly on the skin or in respiratory tract. The pathogenic bacteria are mostly common Staphylococcus, Streptococcus, and Gram-negative bacterium. Infection may be related to a decrease in granulocytes. Here we report a case illustrating the rapid deterioration of FS following the discontinuation of prednisone and methotrexate. During the course of treatment, the patient suffered from ulcerative colitis(UC) and experienced activation of herpesviruses, including HSV1 pneumonia, cheilitis, EBV enteritidis. Ultimately, through an extended period of antiviral and immunomodulatory therapy, the patient's condition improved.\\u003c/p\\u003e\"},{\"header\":\"Case presentation\",\"content\":\"\\u003cp\\u003eA 65-year-old male patient was admitted to our hospital on December 30, 2023, with complaints of \\\"Bilateral hand joint pain for 8 months, diarrhea for 1 months, and fever for 3 days.\\\" 8 months prior to admission, the patient experienced joint pain in both hands accompanied by morning stiffness lasting more than 1 hour, which progressively worsened. At a local hospital, the patient's Rheumatoid Factor (RF) was measured at 159.20 IU/ml, and anti-citrullinated peptide antibody (ACPA) was 287.40 U/ml. Color Doppler imaging of the wrist indicated synovitis thickening in both wrists, leading to a diagnosis of rheumatoid arthritis. Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scores of 36 and 37, respectively, suggested high disease activity, prompting initiation of prednisone and methotrexate antirheumatic therapy. One month prior to admission, the patient had diarrhea, with mucopurulent bloody stools for about 7\\u0026ndash;8 times a day, accompanied by poor appetite and fatigue. The patient stopped methotrexate and was hospitalized in another facility's rheumatology department, where routine blood tests revealed pancytopenia with white blood cell (WBC) count of 1.96\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, hemoglobin (Hb) of 92g/L, platelet(PLT) count 94\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L and absolute neutrophil count of 0.65\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L. Due to concurrent diarrhea, prednisone was discontinued, and anti-infection treatment with meropenem was initiated without improvement. Three days before admission, the patient developed fever and mildly dry cough. He underwent chest and abdominal CT scan, revealing multiple lung abnormalities, mediastinal lymphadenopathy, and diffuse colon wall thickening. Consequently, the patient was transferred to the respiratory department of our hospital for further treatment. Throughout the illness, the patient exhibited poor appetite, mental state and extreme emaciation. The patient's history includes a 30 pack-year smoking habit. Physical examination revealed a high temperature about 40.0 degree centigrade, polypnea with breathing rate of 26 times per minute and finger pulse oxygen saturation of 92%. Multiple ruptures and blisters on the upper and lower lips, with some forming irregular erosion surfaces of varying sizes, surrounded by red halos and black scabs could be observed (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Bilateral enlarged supraclavicular fossa can be palpated as \\\"soybean sized\\\", regular morphology, tenderness, and moderate mobility. Breathing sounds were clear in both lungs and no rhonchus or rale could be heard. There was a mild tenderness around the navel with an active bowel sounds about 7\\u0026ndash;8 beats per minute. Joints examination revealed arthroncus and deformities in both interphalangeal, metacarpophalangeal and wrist joints (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). On admission, the results of blood tests were as follows: WBC 1.96\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L, Hb 76g/L, PLT 52\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L and absolute neutrophil count of 0.25\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e/L,C-reactive protein levels 99.60mg/L, erythrocyte sedimentation rate 112mm/h, procalcitonin 1.83ng/ml, IL-6 712.50pg/ml, ferritin 1520ng/ml, serum EB viral deoxyribonucleic acid 1.35\\u0026times;10\\u003csup\\u003e5\\u003c/sup\\u003ecopies/ml, Herpes simplex virus type-1 IgG antibody 867.61AU/ml. While other biochemical parameters, including hepatic and renal functions, blood glucose, serum lipid, electrolyte, coagulation function and tuberculosis interferon gamma release assay were unremarkable. Sputum pathogens smear and culture, including bacteria, tuberculosis, and fungi were negative. Sputum targeted pathogen second-generation sequencing(tNGS) revealed human herpesvirus type 1(sequence number: 121402). Bronchoalveolar lavage fluid tNGS also revealed human herpesvirus type 1(sequence number: 25588). Ultrasonographic evaluations unveiled enlarged bilateral supraclavicular lymph nodes (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e) and synovial hyperplasia in the wrists (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). Radiological investigations delineated diffuse pulmonary anomalies, especially in both upper lung (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003ea), along with colonic wall thickening (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003ea). Bronchoscope revealed mild airway mucosa hyperemia (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e7\\u003c/span\\u003e). Colonoscopy revealed chronic active inflammation and mucosal erosion (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e8\\u003c/span\\u003e), while in situ hybridization unveiled EBV-encoded RNA in lymphocytes (Fig.\\u0026nbsp;9). Bone marrow scrutiny delineated stable hyperplasia, diminished red and megakaryocyte lines, and anomalous granule morphology.\\u003c/p\\u003e\\n\\u003cp\\u003eOn admission, considering the patient had long-standing rheumatoid arthritis prescribed with prednisone and methotrexate, Chest CT imaging exhibited polymorphic lesions of both upper lungs, blood test showed granulocytopenia, tuberculologist prompted suspicion of secondary pulmonary tuberculosis and bacterial pneumonia. However, evidence towards pulmonary tuberculosis was absent and broad-spectrum anti-bacterial therapy failed. After discontinuation of immunosuppressive medicine, the patient's condition still deteriorated rapidly, with progressive pulmonary involvement and persistent systemic symptoms. Through further examination and discussion, Pulmonary physicians diagnosed HSV1 pneumonia and Antiviral therapy with adenosine and acyclovir was initiated, yet the patient's fever persisted and pulmonary and labial lesions progressed after a week. We conducted multidisciplinary consultations to guide decisions regarding diagnostic tests and treatment. Gastroenterologist diagnosed UC complicated with EBV related enteritidis considering intestinal manifestations and pathological results and advised anti-EBV therapy with Ganciclovir and change from mesalazine tablets to mesalazine granule was essential. Dermatologists recommended recombinant human interferon \\u0026alpha;-2b gel for external use combined with systemic antiviral therapy is necessary for recurrent herpes labialis. Hematologist provided recommendations for the differential diagnosis of pancytopenia. The diagnosis of hemophagocytic syndrome, leukemia, lymphoma lacks sufficient evidence, but we should attach importance to accompanied EBV activation. Intravenous Ganciclovir and immunoglobulin could be a better choice. Besides, granulocyte colony-stimulating factor(G-CSF) could be administered. Rheumatologist identified Felty syndrome as the cause of pancytopenia and advised anti-inflammatory and immunoregulatory therapy with methylprednisolone and immunoglobulin, but methotrexate must be prescribed after pneumonia improved. Pharmaceutical experts recommended antiviral therapy should be extended to two weeks or more depending on the patient\\u0026rsquo;s recovery condition. During the period, physician should pay close attention to adverse drug reactions, such as neurotoxicity and renal dysfunction.\\u003c/p\\u003e\\n\\u003cp\\u003eAfter multidisciplinary discussion, we discontinued acyclovir and initiated intravenous ganciclovir 0.3g q12h for antiviral therapy, recombinant human interferon \\u0026alpha;-2b gel for external use, alongside methylprednisolone 40mg qd ,immunoglobulin 10g qd, mesalazine granule 1.0g qid and G-CSF 200ug tiw. Within 2 weeks, the oral cold sores healed visibly (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003ec), while lung lesions showed significant improvement (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003eb), leading to improvement of respiratory failure and the diarrhea vanished with intestinal CT revealing subsided intestinal edema (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e6\\u003c/span\\u003eb). But the patient still complained fever, joint pain of hands and refractory granulocytopenia. methotrexate (10mg qw) for anti-rheumatic purposes was added, combined with G-CSF at a dose of 200ug biw to elevate leukocyte count. Subsequent one-month follow-up revealed resolution of fever, alleviation of joint pain, and normalization of repeated blood routine examination after G-CSF stopped one month later.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIt is a complex case of multi organ viral activation, as HSV1 pneumonia, cheilitis and EBV enteritidis in the context of RA and UC. Following discontinuation of prednisone and methotrexate due to persistent diarrhea, the patient experienced uncontrolled rheumatic activity and refractory panhemopenia. Despite initial acyclovir being ineffective, subsequent adjustment to ganciclovir and immunoglobulin proved beneficial. Continuation of methylprednisolone, methotrexate, and mesalazine gradually alleviated symptoms associated with FS and UC. Pancytopenia was observed to improve one month later after initiating G-CSF treatment.\\u003c/p\\u003e \\u003cp\\u003eRA combined with UC is not common in clinical practice. It was reported that the occurrence rate of RA combined with IBD is around 5\\u0026ndash;10%\\u003csup\\u003e[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]\\u003c/sup\\u003e. The etiology of UC remains elusive, likely stemming from alterations in gut microbiota, genetic predisposition, and environmental factors. The IL-23/IL-17 axis is a common inflammatory pathway, playing a crucial role in the pathological process by inducing the production of inflammatory cytokines and tissue inflammation in both RA and UC, with IL-23 being a key cytokine\\u003csup\\u003e[\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]\\u003c/sup\\u003e.Short-chain fatty acids, particularly butyrate, produced by gut bacteria, are crucial for intestinal health, known to inhibit pro-inflammatory cytokine formation, enhance epithelial cell integrity, and bolster the gut barrier by fortifying tight junctions\\u003csup\\u003e[\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]\\u003c/sup\\u003e. Studies have shown that fecal microbiota transplantation can induce remission in UC patients, attributed to increased microbial diversity, including butyrate-producing species like Eubacterium hallii\\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e. Conversely, a deficiency in butyrate-producing species and reduced microbial diversity have been observed in RA patients, with intestinal butyrate metabolites implicated in RA autoantibody production and bone erosion\\u003csup\\u003e[\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]\\u003c/sup\\u003e. This contradiction in the roles of short-chain fatty acids may partly explain the rare co-occurrence of UC and RA.Genetic factors also contribute to IBD, with up to 12% of affected individuals having a family history\\u003csup\\u003e[\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e. Among the numerous risk genes associated with IBD, NOD2 is extensively studied. NOD2 encodes a receptor in intestinal epithelial cells and lymphocytes, which recognizes bacterial cell wall dipeptides and triggers pro-inflammatory cytokine production\\u003csup\\u003e[\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]\\u003c/sup\\u003e. Down-regulation of NOD2 gene expression has been linked to reduced inflammation in RA synovial fibroblasts, suggesting a pro-inflammatory role of NOD2 in RA\\u003csup\\u003e[\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]\\u003c/sup\\u003e. Moreover, genome-wide association studies have identified shared gene loci between IBD and RA, as \\u003cem\\u003ePTPN22\\u003c/em\\u003e, \\u003cem\\u003eFCGR2A\\u003c/em\\u003e, \\u003cem\\u003eIL2/IL21\\u003c/em\\u003e, that play important roles in the activation and differentiation of immune cells, as well as cytokine signaling, and jointly participate in the occurrence of IBD and RA \\u003csup\\u003e[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]\\u003c/sup\\u003e. Environmental factors also influence the onset of IBD, with smoking, place of residence, and air pollution being significant contributors. Smoking, in particular, is closely associated with RA pathogenesis, as it induces the expression of enzymes that generate immune-triggering neoantigens\\u003csup\\u003e[\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]\\u003c/sup\\u003e. We performed whole exome sequencing on the patient but did not detect any related genetic variations. Despite residing in rural areas, the patient's prolonged heavy smoking history might have contributed to the development of RA combined with UC. During RA treatment, the patient exhibited diarrhea, elevated serum EBV nucleic acid levels, and systemic lymph node enlargement, prompting consideration of EBV activation. Notably, intestinal pathology revealed strong positive EBER in infiltrated lymphocytes, and active anti-EBV treatment improved symptoms, indicating EBV's potential role in the pathogenesis of UC. Although the exact mechanism remains elusive, studies suggest that EBV infection may induce DNA damage and dysregulate autophagy in colon cells via ERK1/2 signaling pathway. Epigenetic modulation of these processes, such as with 5-Azacytidine, can activate ERK1/2 pathway and mitigate inflammation, suggesting a therapeutic potential for anti-EBV therapy in UC\\u003csup\\u003e[\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eBelonging to the Herpesviridae family, comprising structurally similar, enveloped DNA viruses, more than 100 viruses have been documented, with eight types associated with human infection, categorized into three subfamilies\\u003csup\\u003e[\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]\\u003c/sup\\u003e. While approximately 66% of the global population carries HSV-1, most individuals remain asymptomatic after primary infection, with the virus entering a latent state in ganglia, particularly the trigeminal ganglia. Reactivation of HSV1 can manifest as recurrent perioral or oral lesions (\\\"cold sores\\\") and skin/mucosal lesions when the immune system is compromised\\u003csup\\u003e[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]\\u003c/sup\\u003e. Studies have linked lip herpes occurrence in some individuals during COVID-19 infection to latent herpes simplex reactivation\\u003csup\\u003e[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]\\u003c/sup\\u003e. In this case, concurrent HSV1 pneumonia and cheilitis, coupled with EBV enteritis, involved in the pathogenesis of FS and UC. Further research is warranted to investigate whether EBV can also trigger latent herpes simplex reactivation. HSV1 pneumonia is an uncommon occurrence in respiratory virus infections, with a mere 0.5% incidence in lower respiratory tract infections, usually occurs in specific individuals such as HIV infection, malignant tumors, organ transplantation, or immune dysfunction. Clinical manifestations are atypical, including cough, shortness of breath, fever, hypoxia, may be accompanied by skin and mucosal HSV damage. Chest CT findings present the following characteristics: central lobular nodule with surrounding patchy ground glass lesions (called halo sign), grid shadows, thickening of interlobular septa, diffuse ground glass lesions and pleural effusion. The diagnosis of HSV1 pneumonia contain clinical manifestation, changes of chest CT imaging, and histological evidence or virus isolation from the lower respiratory tract. Regrettably, HSV1 pneumonia wasn\\u0026rsquo;t diagnosed initially for this patient, although HSV1 was detected in the sputum specimen. However, despite antibacterial treatment, the lack of response prompted a reevaluation via bronchoscopy, revealing the persistence of HSV1 in alveolar lavage fluid. Nucleoside antiviral drugs such as acyclovir and ganciclovir are commonly used for HSV1 infection, with the course of treatment is about 9 days in immunocompetent patients and about 17 days in immunocompromised patients \\u003csup\\u003e[\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]\\u003c/sup\\u003e. However, in our case, after a week of acyclovir treatment, the patient\\u0026rsquo;s respiratory failure persisted, and lung lesion enlarged. Perhaps lung injury not only occurred from direct viral damage, but also from immunological damage caused by internal inflammatory storms caused by uncontrolled FS, UC and EBV activation. The changes in the composition and function of the gut microbiota affect the respiratory system through mucosal immune system, and the disruption of the respiratory microbiota can also affect the digestive tract through immune regulation. This interaction between the gut and lungs is called the lung-gut axis. In 2018, an article in Science reported that natural lymphocytes involved in pathological processes such as homeostasis, asthma, and chronic obstructive pulmonary disease (COPD) may migrate from the intestine to the lungs and participate in lung immune responses\\u003csup\\u003e[\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]\\u003c/sup\\u003e. Inflammatory type 2 natural lymphocytes enter the bloodstream through the lymphatic system and function in the lungs. There is current research focusing on the role of the gut-lung axis in various diseases, such as using the modulation of gut microbiota as a novel therapeutic target for COPD\\u003csup\\u003e[\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]\\u003c/sup\\u003e. This all suggests that when lung diseases are combined with intestinal manifestations, attention should be paid to the treatment of intestinal diseases. Following multidisciplinary team discussions, significant improvement occurred after 14 days of intravenous ganciclovir combined with immunoglobulin therapy. During follow-up, HSV1 pneumonia did not recur, and body temperature normalized. Clinical studies have shown HSV1 mortality rates is up to 63% in severe respiratory infection patients\\u003csup\\u003e[\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]\\u003c/sup\\u003e, with those having normal immune function, exhibiting more severe clinical manifestations and higher mortality\\u003csup\\u003e[\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eIf patients with RA experiencing progressive pancytopenia, particularly persistent neutropenia, clinical physicians should be vigilant for FS even in the absence of splenomegaly, and caution should be exercised when discontinuing antirheumatic drugs. Abrupt cessation of methotrexate has been reported to exacerbate FS, with symptoms gradually improving upon methotrexate re-prescribed leading to a gradual increase in neutrophil counts\\u003csup\\u003e[\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]\\u003c/sup\\u003e. The exact pathogenesis of neutropenia in FS remains unclear but may involve an imbalance between neutrophilic production and clearance. Myelodysplasia, primarily granulocyte maturation disorder, leading to reduced neutrophil production\\u003csup\\u003e[\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]\\u003c/sup\\u003e, and increased autoantibodies in circulation, such as histone H3 antibodies and neutrophil extracellular chromatin traps (NETs) autoantibodies, contribute to enhanced neutrophil clearance\\u003csup\\u003e[\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eCorticosteroids, methotrexate, and recombinant human colony-stimulating factor are considered the main therapeutic drugs\\u003csup\\u003e[\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]\\u003c/sup\\u003e, while methotrexate is considered the most effective and well tolerated choice among antirheumatic drugs for improving RA symptoms and neutropenia. Therefore, it is recommended as the first-line treatment for such patients. A study by the Peking Union Medical College Hospital in China reported 17 cases of FS collected over the past 10 years. Successful treatment outcame in most cases with methylprednisolone (30-60mg Qd) and methotrexate (5-15mg qw), while splenectomy was considered for cases with accompanying splenomegaly and poor drug treatment response\\u003csup\\u003e[\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]\\u003c/sup\\u003e. In approximately 80% of cases, neutrophil counts can continue to normalize after splenectomy for more than 6 months. If neutrophil counts could not be elevated by methotrexate, rituximab may be considered, with nearly two-thirds of cases showing normalization after the first course of rituximab treatment, as indicated by systematic review of case reports\\u003csup\\u003e[\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eWe reported an uncommon case of HSV1 pneumonia accompanied by EBV enteritis. Considering the patient developed a multi system including lips, lung, intestinal tract, we further discovered the underlying immune disorders of FS and UC, that probably induced tissue damage through enlarged inflammatory imbalance as our initial antiviral treatment is unsatisfactory. What role does the virus play exactly in the pathogenesis of inflammatory diseases? It may be the pathogenesis, comorbidities, or clinical outcomes, and function diversely. But still now, these researches are insufficient and it deserves more attentions in the future.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cp\\u003eACPA: anti-citrullinated peptide antibody; COPD: chronic obstructive pulmonary disease; CDAI: clinical disease activity index; EBV: epstein-barr virus; FS: felty syndrome; G-CSF: granulocyte colony-stimulating factor; HSV1: herpes simplex virus type 1; Hb: hemoglobin; NETs: neutrophil extracellular chromatin traps; PLT: platelet; RA: rheumatoid arthritis; SDAI: simplified disease activity index; tNGS: targeted pathogen second-generation sequencing; UC: ulcerative colitis; WBC: white blood cell.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026rsquo;\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eGuarantors of integrity of entire study, Liu Da; study concepts/study design or data acquisition or data analysis/interpretation, Jianjun He, Liu Da; manuscript drafting or manuscript revision for important intellectual content, Jianjun He,Liu Da; Contribution of diagnosis and treatment opinions, Da Liu, Shali Jiang, Sai Wang, Yongfeng Zhu, Yafei Yin, Jingjiang Yao; agreement to ensure any questions related to the work are appropriately.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis work was supported by the Youth program of the Hunan Provincial Natural Science Foundation of China (2021JJ40622), the National Natural Science Foundation of China (82300042), Changsha Natural Science Foundation of China (kq2007081) and Clinical Medical Research 4310 Project of University of South China (20214310NHYPY04).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe case report was approved and supervised by The Afffliated Changsha Central Hospital, Hengyang Medical School, University of South China (committee\\u0026rsquo;s reference number：KY-2024-059-02)\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eInformed consent was obtained from the patient.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interest.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n \\u003cli\\u003eJellinge M E, Hansen F, Coia J E, et al. Herpes simplex virus type 1 pneumonia\\u0026mdash;a review[J]. Journal of Intensive Care Medicine, 2021, 36(12): 1398-1402.\\u003c/li\\u003e\\n \\u003cli\\u003e[1]Simoons-Smit A M, Kraan E M, Beishuizen A, et al. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: real pathogen or innocent bystander?[J]. Clinical microbiology and infection, 2006, 12(11): 1050-1059.\\u003c/li\\u003e\\n \\u003cli\\u003eLiu R, Wang M, Zhang L, et al. The clinicopathologic features of chronic active Epstein-Barr virus infective enteritis[J]. Modern Pathology, 2019, 32(3): 387-395.\\u003c/li\\u003e\\n \\u003cli\\u003ePezhouh M K, Miller J A, Sharma R, et al. Refractory inflammatory bowel disease: is there a role for Epstein-Barr virus? A case-controlled study using highly sensitive Epstein-Barr virus\\u0026ndash;encoded small RNA1 in situ hybridization[J]. Human pathology, 2018, 82: 187-192.\\u003c/li\\u003e\\n \\u003cli\\u003eRohekar S, Chan J, Tse S, et al. Characteristics associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis. 2009;68(2): 364-9.\\u003c/li\\u003e\\n \\u003cli\\u003eT, et al. Rheumatoid arthritis in patients with inflammatory bowel disease: a retrospective observational study. World J Gastroenterol. 2017;23(39):7179-7186.\\u003c/li\\u003e\\n \\u003cli\\u003eLin L, Zhang J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases[J]. BMC immunology, 2017, 18: 1-25.\\u003c/li\\u003e\\n \\u003cli\\u003eParamsothy S, Nielsen S, Kamm M A, et al. Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis[J]. Gastroenterology, 2019, 156(5): 1440-1454. e2.\\u003c/li\\u003e\\n \\u003cli\\u003eHe J, Chu Y, Li J, et al. Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis[J]. Science advances, 2022, 8(6): eabm1511.\\u003c/li\\u003e\\n \\u003cli\\u003eLiu J Z, Anderson C A. Genetic studies of Crohn\\u0026apos;s disease: past, present and future[J]. Best Practice \\u0026amp; Research Clinical Gastroenterology, 2014, 28(3): 373-386.\\u003c/li\\u003e\\n \\u003cli\\u003ePhilpott D J, Sorbara M T, Robertson S J, et al. NOD proteins: regulators of inflammation in health and disease[J]. Nature Reviews Immunology, 2014, 14(1): 9-23.\\u003c/li\\u003e\\n \\u003cli\\u003eKim H W, Kwon Y J, Park B W, et al. Differential expressions of NOD-like receptors and their associations with inflammatory responses in rheumatoid arthritis[J]. Clin Exp Rheumatol, 2017, 35(4): 630-7.\\u003c/li\\u003e\\n \\u003cli\\u003eLees C W, Barrett J C, Parkes M, et al. New IBD genetics: common pathways with other diseases[J]. Gut, 2011, 60(12): 1739-1753.\\u003c/li\\u003e\\n \\u003cli\\u003eMakrygiannakis D, Hermansson M, Ulfgren A K, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells[J]. Annals of the rheumatic diseases, 2008, 67(10): 1488-1492.\\u003c/li\\u003e\\n \\u003cli\\u003eSantarelli R, Evangelista L, Pompili C, et al. EBV infection of primary colonic epithelial cells causes inflammation, DDR and autophagy dysregulation, effects that may predispose to IBD and carcinogenesis[J]. Virus Research, 2023, 338: 199236.\\u003c/li\\u003e\\n \\u003cli\\u003eLan K, Luo M H. Herpesviruses: epidemiology, pathogenesis, and interventions[J]. Virologica Sinica, 2017, 32: 347-348.\\u003c/li\\u003e\\n \\u003cli\\u003eArduino P G, Porter S R. Herpes Simplex Virus Type 1 infection: overview on relevant clinico‐pathological features[J]. Journal of oral pathology \\u0026amp; medicine, 2008, 37(2): 107-121.\\u003c/li\\u003e\\n \\u003cli\\u003eShafiee A, Teymouri Athar M M, Amini M J, et al. Reactivation of herpesviruses during COVID‐19: A systematic review and meta‐analysis[J]. Reviews in medical virology, 2023, 33(3): e2437.\\u003c/li\\u003e\\n \\u003cli\\u003eSchuller D. Lower respiratory tract reactivation of herpes simplex virus: comparison of immunocompromised and immunocompetent hosts[J]. Chest, 1994, 106(1): 3S-7S.\\u003c/li\\u003e\\n \\u003cli\\u003eMj\\u0026ouml;sberg J, Rao A. Lung inflammation originating in the gut[J]. Science, 2018, 359(6371): 36-37.\\u003c/li\\u003e\\n \\u003cli\\u003eBudden K F, Shukla S D, Bowerman K L, et al. Faecal microbial transfer and complex carbohydrates mediate protection against COPD[J]. Gut, 2024.\\u003c/li\\u003e\\n \\u003cli\\u003eL\\u0026oacute;pez-Giraldo A, Sialer S, Esperatti M, et al. Viral-reactivated pneumonia during mechanical ventilation: is there need for antiviral treatment?[J]. Frontiers in Pharmacology, 2011, 2: 66.\\u003c/li\\u003e\\n \\u003cli\\u003eHamsho S, Alannouf I, Ashour A A. Rapidly Progressive Felty Syndrome After Sudden Discontinuation of Methotrexate: A Case Report and Review of Literature[J]. International Medical Case Reports Journal, 2022: 473-477.\\u003c/li\\u003e\\n \\u003cli\\u003eDancey J T, Brubaker L H. Neutrophil marrow profiles in patients with rheumatoid arthritis and neutropenia[J]. British Journal of Haematology, 1979, 43(4): 607-617.\\u003c/li\\u003e\\n \\u003cli\\u003eHellmich B, Csernok E, Schatz H, et al. Autoantibodies against granulocyte colony‐stimulating factor in Felty\\u0026apos;s syndrome and neutropenic systemic lupus erythematosus[J]. Arthritis \\u0026amp; Rheumatism, 2002, 46(9): 2384-2391.\\u003c/li\\u003e\\n \\u003cli\\u003eRashba E J, Rowe J M, Packman C H. Treatment of the neutropenia of Felty syndrome[J]. Blood reviews, 1996, 10(3): 177-184.\\u003c/li\\u003e\\n \\u003cli\\u003e宋爱凤,张莉,徐东等.费尔蒂综合征17例临床分析[J].中华临床免疫和变态反应杂志,2021,15(05):534-539.\\u003c/li\\u003e\\n \\u003cli\\u003eNarv\\u0026aacute;ez J, Domingo-Domenech E, G\\u0026oacute;mez-Vaquero C, et al. Biological agents in the management of Felty\\u0026apos;s syndrome: a systematic review[C]//Seminars in arthritis and rheumatism. WB Saunders, 2012, 41(5): 658-668.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"HSV-1 pneumonia, Felty syndrome, EBV enteritidis, ulcerative colitis\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4227348/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4227348/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground: \\u003c/strong\\u003eFelty syndrome (FS), as a rare syndrome, primarily presents as splenomegaly and neutropenia in the context of rheumatoid arthritis (RA).although Inflammatory bowel disease and rheumatoid arthritis are both autoimmune diseases, they only appear together in rare cases.Herpesviruses can be activated in this pathological process, thereby precipitating associated infections, including severe herpes simplex virus type 1(HSV1) pneumonia, and Epstein-Barr virus (EBV) enteritidis in our case.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCase presentation: \\u003c/strong\\u003eHere, we report a case illustrating the rapid deterioration of FS following the discontinuation of prednisone andmethotrexate. During the course, this patient exhibited fever, diarrhea, cold sores, and finally be dignosed severe HSV1 pneumonia, cheilitis, EBV enteritidis and ulcerative colitis.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions: \\u003c/strong\\u003eIn patients with rheumatoid arthritis, sudden cessation of anti rheumatic drugs may induce Felty syndrome, which in turn can induce the activation of herpesvirus in the body, leading to a series of herpesvirus related infections, such as ,cheilitis, pneumonia and enteritis. Early intravenous use of sufficient antiviral drugs and timely initiation of antirheumatic drugs may be a more appropriate solution.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Severe HSV1 pneumonia and EBV enteritidis in a patient with Felty syndrome and ulcerative colitis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-04-19 18:59:32\",\"doi\":\"10.21203/rs.3.rs-4227348/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"a67b083c-b237-44c0-b745-b9146b1e3490\",\"owner\":[],\"postedDate\":\"April 19th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-05-30T18:59:12+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-04-19 18:59:32\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4227348\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4227348\",\"identity\":\"rs-4227348\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}