Late-onset damage from occupational asbestos exposure: case report

Introduction

Retroperitoneal fibrosis (RPF) is a rare condition characterized by the progressive transformation of retroperitoneal adipose tissue into fibrous tissue. Despite its rarity, the pathophysiology of RPF remains poorly understood. However, recent advancements in imaging techniques have enhanced the diagnosis of RPF, increasing awareness of this condition in the context of various abdominal and vascular symptoms (1).

RPF often results in complications such as urinary obstruction and compression of the abdominal aorta, particularly in its subrenal portion, as well as involvement of the iliac arteries and inferior vena cava. Patients typically present with symptoms including abdominal pain, low back pain, and renal colic. Furthermore, alterations in the patient’s general condition due to the inflammatory processes associated with RPF are frequently observed (2).

Differentiating between idiopathic RPF and secondary forms can be clinically challenging. Therefore, a comprehensive medical history is essential, encompassing factors such as occupational exposure, smoking habits, medication use, prior radiotherapy, and previous surgeries. Complementary diagnostic tools—including laboratory tests, imaging studies, and biopsies—are crucial for accurate diagnosis (3).

We describe a case of a patient whose RPF was linked to asbestos exposure after carefully excluding other differential diagnoses. Remarkably, the patient’s condition improved significantly following an innovative treatment approach that combined corticosteroid therapy with azathioprine (AZA). This management led to notable clinical and biological improvements, as well as radiological regression of the fibrosis. We present this case in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-24-164/rc).

Case presentation

We present the case of a 64-year-old male patient who worked as an automotive sheet metal worker and was exposed to asbestos for twenty-five years. He was admitted following the onset of right low back pain that had persisted for one week, without any accompanying symptoms. The patient exhibited signs of apyrexia and a deterioration in his general condition, characterized by asthenia, anorexia, and a weight loss of 6 kg over the past year.

A thorough medical history revealed no toxic habits, particularly smoking, and there was no history of radiotherapy or previous surgeries. The patient denied any prior tuberculosis infection or known medication use.

Clinical examination did not reveal any signs of tumor syndrome, pulmonary or cardiac involvement, lower extremity edema, macroglossia, or bruising. However, sensitivity was noted in the right flank, along with a firm, mobile, well-defined left thyroid nodule measuring approximately one centimeter that was non-tender.

Ultrasound imaging of the kidneys and bladder showed moderate right ureteropyelocalicial dilation. A subsequent computed tomography (CT) scan revealed circumferential fusiform thickening of the right primary iliac artery wall [measuring 45 Hounsfield unit (HU)], which enhanced with contrast medium. The thickening measured 17 mm at its maximum thickness and extended over 50 mm, leading to compression of the iliac ureter at this level and resulting in moderate uretero-hydronephrosis upstream. Additionally, there was thickening of the ureteropelvic wall and significant infiltration of the perirenal fat (Figure 1).

Figure 1 Coronal view of abdominal-pelvic CT scan. The arrow indicates the right RPF. CT, computed tomography; RPF, retroperitoneal fibrosis.

Biological assessment indicated an inflammatory syndrome with a markedly elevated C-reactive protein (CRP) level of 130.8 mg/L, alongside procalcitonin at 0.02 ng/mL, hyperleukocytosis at 11,500/mm³, neutrophils at 7,950/mm³, and hyperfibrinogenemia at 5.6 g/L. Renal function remained preserved (urea at 0.42 g/L and creatinine at 5.1 mg/L), and the complete blood examination was germ-free without leukocyturia or hematuria. To further substantiate the etiological diagnosis, a protein electrophoresis test was performed, which returned normal results.

Testing for Koch’s bacillus from induced sputum and urine over three consecutive days yielded negative results on direct examination and Löwenstein culture. Additionally, the Interferon Gamma Release Assay (IGRA) was also negative.

The chest CT scan revealed bilateral pulmonary parenchymal nodules and micronodules of nonspecific disposition, with no evidence of interstitial involvement or pulmonary fibrosis (Figure 2).

Figure 2 Horizontal section of CT scan of the chest showing bilateral pulmonary parenchymal nodules and micronodules. CT, computed tomography.

Tumor markers, including prostate-specific antigen (PSA), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA), were all within normal limits. Antinuclear antibody tests returned negative results, and the IgG4 assay was also normal. Additionally, 24-hour proteinuria was negative, and a lip biopsy with Congo red staining showed no abnormalities. A biopsy for RPF was not performed.

In the exploratory assessment of the left thyroid nodule, cervical ultrasound identified a well-circumscribed, moderately hypoechoic nodular formation in the upper left polar region, classified as EUTIRADS 3. Thyroid hormone levels [thyroid stimulating hormone (TSH), T3, and T4] were normal.

Therapeutically, the patient underwent the placement of a right JJ stent (Figure 3) and was initiated on full-dose corticosteroid therapy for six weeks, followed by a gradual tapering along with AZA at a dosage of 150 mg per day.

Figure 3 Coronal view of abdominal-pelvic CT scan after right ureteral stenting. The arrow shows the right sided double J stent. CT, computed tomography.

The clinical course was favorable, marked by a regression of right low back pain and an overall improvement in the patient’s general condition. Biologically, the inflammatory syndrome resolved. At the 6-month follow-up CT scan after treatment, complete regression of the fibrous sheath around the right primary iliac pedicle was observed. However, there was persistent mild right pyelocaliceal dilation with the JJ stent still in place. Throughout the treatment period, there were no adverse or unanticipated events reported.

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In 1905, French urologist Albarran first described RPF as stenosing peri-ureteritis.

By 1948, it was recognized as a distinct clinical entity associated with Ormond (4). The incidence of RPF is notably higher in men aged 40 to 60 years. While idiopathic RPF is the most prevalent form, it remains a diagnosis of exclusion. Previously, it was believed that idiopathic RPF resulted from a local inflammatory reaction to antigens present in atherosclerotic plaques of the abdominal aorta. However, recent clinical and biological findings have prompted a reevaluation of the pathophysiogenesis of RPF. The presence of an inflammatory syndrome during the acute phase and its frequent association with autoimmune diseases suggest that RPF may represent either a manifestation of an autoimmune disorder or a systemic inflammatory disease (5). In approximately one-third of cases, RPF can be secondary to medications (such as ergot derivatives, methysergide, methyldopa, hydralazine, and beta-blockers), infections (including tuberculosis, histoplasmosis, and actinomycosis), or malignancies (such as lymphomas, sarcomas, and metastases). A thorough medical history should investigate any history of irradiation, surgery, or abdominal trauma. Additionally, rarer causes such as histiocytosis, Erdheim-Chester disease, and amyloidosis should not be overlooked (6). Numerous diseases are associated with asbestos exposure. While pleural involvement is predominant—manifesting as pleural plaques, extensive pleural fibrosis, benign pleural effusions, or mesothelioma—parenchymal involvement primarily presents as Hanke’s round atelectasias, fibrosis, and bronchopulmonary cancer. Although retroperitoneal fibrosis is less commonly reported in this context, it has been associated with peritoneal mesotheliomas and various cancers including gastric, renal, oropharyngeal, laryngeal cancers, and even leukemias (7). The etiopathogenesis of RPF remains enigmatic. It has been proposed that local inflammatory responses to antigens in atherosclerotic plaques may initiate chronic inflammatory processes. Additionally, evidence suggests that a significant proportion of idiopathic RPF can be classified within the spectrum of IgG4-related disease, which affects multiple organs and is characterized by lymphoplasmatic infiltration and fibrosis. Overall, while idiopathic RPF is often viewed as a localized reaction to vascular pathology, emerging evidence indicates that it may also reflect broader systemic conditions. This complexity underscores the need for continued research into the underlying mechanisms and potential treatment strategies for this challenging condition.

Exposure to asbestos is a causal factor in the development of RPF (8). According to the Agency for Toxic Substances and Disease Registry (ATSDR) (9) and the Occupational Safety and Health Administration (OSHA), asbestos exposure remains a major concern (10). The patient’s 25 years of experience in automotive sheet metal work significantly predisposes him to the development of RPF. A Finnish case-control study involving 43 patients found that the risk of developing RPF increased ninefold after 10 years of occupational exposure to asbestos. The latency period in this study was typical for asbestos-related diseases, exceeding 20 years in all but two cases (11).

In cases of occupational exposure to asbestos, RPF must be classified as a notifiable occupational disease. The diagnosis is typically established through a combination of anamnestic, clinical, radiological, and therapeutic evidence. A biopsy for RPF is indicated only in situations of diagnostic uncertainty or therapeutic failure. When performed, the biopsy reveals an extracellular matrix composed of type I collagen fibers organized into thick, irregular bundles surrounding the retroperitoneal vessels. Chronic exposure to asbestos over many years can significantly impact respiratory function prior to the onset of RPF. However, in our patient, respiratory involvement was not clinically evident and was only identified through imaging, which revealed nodular and micronodular patterns. CT is an essential diagnostic tool for detecting abnormalities in individuals with at least 20 years of occupational asbestos exposure. Lesions may be present in approximately 4.4% of cases as pleural plaques and in 1.4% as other abnormalities, including round atelectasis, asbestosis, thickening of the visceral pleura, bronchopulmonary cancer, and mesothelioma. Pulmonary nodules are observed in about 31.8% of cases and are generally stable over time (12). When urinary obstruction is suspected, a urogram is performed to visualize RPF, identify potential etiologies, and assess the therapeutic response. This comprehensive approach ensures that patients receive appropriate management for their condition while monitoring for any associated complications related to asbestos exposure.

The primary treatment for RPF is corticosteroid therapy in combination with immunosuppressants. The main therapeutic objectives in managing idiopathic RPF include halting the progression of the fibro-inflammatory reaction, addressing vascular and urinary complications, and preventing recurrences. Corticosteroids are the most commonly utilized medications, as they suppress the synthesis of various cytokines involved in the acute inflammatory response, reduce inflammation, and inhibit collagen synthesis. Consequently, corticosteroid therapy not only alleviates symptoms but also decreases the size of the RPF. Currently, the dosage and duration of corticosteroid treatment are not standardized. However, it is generally recommended to administer prednisone or prednisolone at a dosage of 0.5 to 1 mg/kg/d for an average duration of 2 years (13). Patients exhibiting elevated CRP levels tend to demonstrate a more favorable therapeutic response to corticosteroids compared to those with lower CRP values (14). The presence of an inflammatory syndrome is likely indicative of active RPF, which is responsive to treatment, as observed in our patient. In summary, corticosteroid therapy remains the cornerstone of treatment for idiopathic RPF. Ongoing research into optimizing treatment regimens and exploring alternative therapies may enhance patient outcomes while minimizing potential side effects associated with long-term corticosteroid use.

Cortisone-sparing treatment options for RPF represent a valuable strategy for preventing relapses. This approach includes the use of immunosuppressants such as cyclophosphamide, AZA, methotrexate, and mycophenolate mofetil, as well as other less specific agents like tamoxifen and colchicine (15). However, there is currently no established literature regarding recommended cortisone-sparing treatments specifically for secondary RPF related to asbestos exposure. The decision to utilize AZA in our patient is both novel and promising for medium-term outcomes. Ongoing follow-up for professional RPF associated with asbestos should involve comprehensive clinical, biological, and radiological monitoring. The frequency and duration of pleuropulmonary or abdominal assessments have not yet been standardized, allowing clinicians the flexibility to tailor their approach based on the patient’s evolving clinical profile. The potential for both early and late recurrences remains a concern. Bronchopulmonary cancer (BPC) is more prevalent among populations exposed to asbestos, even in the absence of pulmonary fibrosis. Additionally, with equivalent cumulative exposure, asbestosis significantly increases the risk of developing BPC, while pleural plaques are associated with an elevated risk of both BPC and mesothelioma. In summary, a multidisciplinary approach to managing RPF, particularly in patients with a history of asbestos exposure, is essential. This includes considering cortisone-sparing therapies and ensuring vigilant long-term monitoring to mitigate the risks of recurrence and associated malignancies (16).

Conclusions

RPF is a rare inflammatory disease whose diagnostic and therapeutic approaches remain largely undefined.

Prolonged exposure to asbestos is a significant yet often overlooked cause of RPF, and it is classified as a notifiable occupational disease. Continuous post-exposure monitoring is essential for the early detection of complications.

In cases of benign RPF, corticosteroid therapy remains the primary treatment option, often combined with urinary drainage procedures in instances of obstruction. The use of immunosuppressants, such as AZA, has shown promise in preventing relapses, providing a valuable alternative for patients requiring long-term management.

Looking forward, several recommendations can enhance the understanding and treatment of RPF such as standardization of diagnostic protocols, long-term monitoring framework, research on treatment modalities and increasing awareness among healthcare professionals. Furthermore, multidisciplinary approach encouraging collaboration among specialists can ensure holistic care and enhance diagnostic accuracy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-24-164/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-24-164/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-24-164/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study are in accordance with the ethical standards of the institutional and/or national research comittee(s). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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