AUCTORES
Globalize your Research
Case Report
*Corresponding Author: Janaki Deepak, Division of Pulmonary and Critical Care Medicine, Baltimore VA Medical Health Center, Baltimore, MD 21201, USA.
Citation: Janaki Deepak, Blaine Kenaa. (2020) Caplan’s syndrome with a twist. International Journal of Clinical Case Reports and Reviews. 2(1); DOI:10.31579/2690-4861/007
Copyright: © 2020 Janaki Deepak, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 19 December 2019 | Accepted: 16 January 2020 | Published: 22 January 2020
Keywords: Caplan’s syndrome; pulmonary nodules; leflunomide; hydroxychloroquine.
Caplan’s syndrome is seen in patients with rheumatoid arthritis (RA) and chronic silica inhalation. We present a patient with RA who presented with multiple pulmonary nodules. Biopsy of the nodules revealed silica crystals under polarized light. He continued treatment for RA and his pulmonary nodules remained stable. However, he subsequently developed renal failure with nephrotic range proteinuria. We discuss silica and the associated autoimmunity in patients with chronic occupational exposure.
Caplan’s syndrome also known as rheumatoid pneumoconiosis is a disease entity that is seen in patients with rheumatoid arthritis (RA) exposed to chronic silica and inorganic dust [1,2]. Classically, they form peripheral well-defined pulmonary nodules with characteristic silica retained in the necrobiotic center. In addition, epidemiological data has shown some association with silica and autoimmunity [3]. We present a case of silica and asbestosis exposure in a patient with rheumatoid arthritis who developed rheumatoid pneumoconiosis and subsequent renal failure. We highlight this rare disease, progression as well as other associated complications.
CASE PRESENTATION
A 73 y/o man with no smoking history and a diagnosis of RA was referred to the pulmonary clinic for multiple pulmonary nodules in a peri-lymphatic pattern (Figure 1).Patient was noted to have progressive pulmonary nodules that have been increasing in size (Figure 2).
His rheumatologist planned to start him on TNF-alpha inhibitors for his RA and wanted to evaluate for infections and malignant causes prior to proceeding with the treatment. He was asymptomatic and denied any respiratory complaints. At the time of presentation, he was being treated with leflunomide, hydroxychloroquine and sulfasalazine. Pt is a Navy veteran with exposure to asbestos while he was in the Navy. Following his discharge from the Navy, he worked 10 years overseeing production of plastic and metal parts for guided radar systems. He then transitioned to working in residential construction, hanging, siding and replacing windows. He also worked on restoring brick on old houses by stripping off paint for about 5 years.
Pulmonary function test (PFT) revealed mild obstructive ventilator defect with FEV1/FVC 66%, FEV1 of 3.13L, 94% predicted. He underwent bronchoscopy with transbronchial biopsies of the right upper lobe nodules. Pathology revealed a necrotic tissue (Figure 3) with central silica crystals visualized under polarized light which was consistent with silico-anthracotic nodules. The biopsies were negative for malignancy. There was no evidence of infection on bronchoalveolar lavage. His AFB and fungal cultures were also negative.
Autoimmunity is not isolated to patients with RA, nor is it only seen in silica. Epidemiological data suggests that similar correlation exists between asbestos exposure and autoimmunity [3]. In areas with significant silica exposure, there is an increased incidence in other autoimmune diseases such as systemic lupus erythematosus (SLE) with more male predominance [3]. In select animal models, exposure to silica and asbestos result in elevated ANA titers with IgG and C3 kidney deposits, simulating SLE-like disease. Following inhalation to the lungs, silica particles can mobilize to the kidney resulting in end stage renal disease in 5% of exposed individuals [3,4]. Our patient eventually developed nephrotic range proteinuria with renal biopsy confirming MCD and FSGS overlap. It is unclear what role the silica exposure played in the development of the kidney disease but his kidney biopsy did not reveal any immune deposits or silica crystals [5]. In a meta-analysis by Möhner et al, they highlighted the challenge in accurately characterizing the causal relationship between Silica and chronic non-malignant renal disease due to significant lag time between exposure and diagnosis [5]. Furthermore, it is difficult to identify a dose dependent relationship that could be attributed to an overall increase in mortality.Three years following his biopsy, the patient presented with lower extremity edema and dyspnea on exertion. He was found to have worsening renal failure with subsequent renal biopsy showing a mixture of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). The staining was negative for amyloid and no silica deposits were identified. He also underwent right heart catheterization that showed mild pulmonary hypertension with mean PAP of 33. CT chest did not show worsening or progression of the nodules.
Disccusion
Since it was first described by Caplan in 1953, the exact correlation between RA, pneumoconiosis and autoimmunity has been a topic of debate [2]. Silica is recognized as a pathogen associated molecular pattern (PAMP) which stimulates macrophages and subsequent release of cytokines like TNF-alpha and IL-1 [1]. This process triggers a cyclical pattern of macrophage apoptosis and chronic inflammation generating fibroblast deposits and tissue destruction. The cytokines further stimulate the adaptive immune system with subsequent increased production of autoantibodies and immune complex [1].
As an antigen, silica induces stimulation of bronchus associated lymphoid tissue (BALT), which is the mucosa associated lymphoid tissue (MALT) of the lung [3,6]. In normal healthy adults, BALT is either absent or if present lacks functional germinal centers. However, with chronic stimulation in the presence of an antigen, smoking or autoimmune diseases such as RA and SLE, it can mature with formation of the four germinal centers, triggering a malignant transformation [6]. Though silica is classified as a carcinogen by the International Agency for research on cancer (IARC), there is no documented association between silica and malignant lymphoma [4,7].
Following the diagnosis of Caplan’s syndrome, PFTs usually remain normal or have a mild obstructive physiology [1]. However, there have been case reports where patients have presented with a mixed restrictive and obstructive pattern depending on extent of the nodules, progressive parenchymal distortion and associated fibrosis [8]. Usually, the necrobiotic nodules remain peripheral and asymptomatic but they can also cavitate, enlarge and coalesce resulting in progressive massive fibrosis (PMF) [1]. In a retrospective case series by Constantinidis et al, they were able to demonstrate that patients with PMF had reduced vital capacity and significant airflow obstruction compared to patients with lesions that are localized to the periphery [9]. Our patients’ pulmonary status has remained the same over the course of 3 years.
In conclusion, Caplan’s syndrome remains a rare disease entity. Clear understanding of the exact causality between silica, RA and autoimmunity remains unclear. Diagnosis requires a thorough occupational health history that spans the patient’s adult life as well as second hand exposures during childhood. Differential diagnosis for these nodules includes lymphoma, tuberculosis, sarcoidosis or metastasis. Diagnostic sampling of the nodule is necessary not only to identify the necrobiotic nodules but to also rule out other similar disease processes. There is currently no evidence-based guideline on ways to routinely follow up these nodules and each case is addressed as an individual entity. However, patients should be monitored for rare complications such as hemoptysis or pneumothorax from the cavitated nodules as well as end stage pulmonary fibrosis.
LEARNING POINTS/TAKE HOME MESSAGES
There is no current guideline for silica exposure and cancer surveillance. It is recommended that patients follow age appropriate cancer screenings.
Funding: This research received no external funding. However, author Janaki Deepak has grant funding through National Institutes of Health, Laboratory of Human Carcinogenesis, CCR, NCI-NO2RC-57700.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
