IgG4-related retroperitoneal fibrosis induced by nivolumab and ipilimumab in a patient with non-small cell lung cancer: A case report.

IgG4-related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4-related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80-year-old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography-guided biopsy of the retroperitoneum showed B cell-dominant lymphocyte infiltration consistent with IgG4-related retroperitoneal fibrosis and characteristic CD8-positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4-related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4-related retroperitoneal fibrosis can occur as an immune-related adverse event when administering anti-PD-1 and anti-CTLA-4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune-related adverse event.

Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan.

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

Serial 68Ga-FAPI PET/CT After Treatment of Immunoglobulin G4-Related Pancreatitis and Retroperitoneal Fibrosis.

ABSTRACT: Immunoglobulin G4 (IgG4)-related disease is a fibroinflammatory condition involving diverse organs. We report a case of IgG4-related pancreatitis and retroperitoneal fibrosis with serial 68Ga-FAPI PET/CT scans after treatment. A 64-year-old man presented with left flank and epigastric pain. Laboratory, abdominal CT, and 68Ga-FAPI PET/CT findings were suggestive of IgG4-related pancreatitis and retroperitoneal fibrosis. Histology of the pancreas confirmed IgG4-related pancreatitis. The follow-up PET/CT scans after treatment with steroid therapy showed regression of 68Ga-FAPI uptake in the pancreas and periureteral soft tissue. The changes on 68Ga-FAPI PET/CT scans were much more prominent compared with the CT scans.

IgG4-related retroperitoneal fibrosis with acute kidney injury: a case report and literature review.

IgG4-related retroperitoneal fibrosis is a rare cause of renal dysfunction that usually manifests as obstructive nephropathy (sometimes with extrarenal manifestations). Due to the non-specific symptoms at the onset of the disease and often latent course, special laboratory and instrumental examination methods are usually needed to establish a diagnosis. The article describes a clinical case of a relapse of IgG4-related retroperitoneal fibrosis in a 53-year-old patient, who developed bilateral ureterohydronephrosis with postrenal acute kidney injury after the withdrawal of glucocorticoid therapy. The patient underwent bilateral percutaneous nephrostomy and resumed glucocorticoids at a dose of 30 mg/day. Postobstructive diuresis was 22 L. Treatment resulted in a complete normalization of the creatinine level and transient hypokalemia, which was eliminated with potassium medications. At the final stage of the treatment, bilateral stenting of both ureters was performed with a tapering of glucocorticoids to 5 mg per day with CT control of the retroperitoneal space after 5 months. A clinical case demonstrates that an interruption of glucocorticoid treatment in patients with IgG4-related retroperitoneal fibrosis can lead to ureterohydronephrosis with the development of acute kidney injury. In such cases, stenting of the ureters could be considered an optimal therapeutic option.

Successful therapy of retroperitoneal fibrosis due to IgG4-related disease with rituximab, cyclophosphamide and glucocorticoids followed by maintenance therapy wit ritutixmab.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. Common symptoms at onset include lower back, abdominal or flank pain, and constitutional symptoms such as malaise, fever, and anorexia and weight loss. Pain is frequently referred to the hip, to the groin and to the lateral regions of the leg, with nocturnal exacerbations, and typically does not modify with position. We report a case of 56 year-old male with recurrent lower back pain and lower abdominal pain. Contrast-enhanced computed tomography and was suggestive of retroperitoneal fibrosis and unilateral ureteral occlusion. Histologic examination with immunohistochemical staining for IgG4 demonstrate IgG4-related retroperitoneal fibrosis. Therapy was started with prednison 1 mg/kg, but the tolerance of this dose was poor. Therefore the therapy was switched to combination of rituximab 375 mg/ m2 on day 1, cyclophosphamide 300 mg/m2 mg infusion and dexamethasone 20 mg total dose infusion on day 1 and 15 in 28 days cycle. FDG-PET/CT control in fourth month showed residual accumulation of FDG in retroperitoneal fibrotic mass, and therefore the therapy was prolonged to 8 month. The subjective symptoms of this diseases disappeared in the 8th month. Then the maintenance therapy, administration of rituximab in 6 month interval, was started. The activity of this disease be further evaluated by FDG-PET/CT imagination. Glucocorticoids are considered the cornerstone of therapy. The use of other immunosuppressive agents, including cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil and biological agents such as rituximab, tocilizumab and infliximab and sirolimus have been reported as a valuable option mostly in case reports, cases series and small studies. This agents allowed to reduce cumulative dose of glucocorticoids and its adverse effects. Therefore in our patients we preferred combination of rituximab cyclophosphamide s dexamethasone with lover dose of prednisonem. This combination is preferable for patients who cannot tolerate glucocorticoids or who are likely to suffer from significant glucocorticoids -related toxicity.

Rituximab in the management of retroperitoneal fibrosis: A single tertiary rheumatology care center experience.

AIM: To investigate the clinical and radiological outcomes and glucocorticoid-sparing effect of rituximab therapy in 13 patients with retroperitoneal fibrosis (RPF). METHODS: We analyzed the data of both glucocorticoid-naive and glucocorticoid-resistant RPF patients who were treated with rituximab. Demographic features, positron emission tomography computed tomography (PET-CT) findings, and clinical and histopathologic outcomes were collected retrospectively. RESULTS: We evaluated the data of 13 RPF patients (8M/5F). The median follow-up duration was 28 months (interquartile range [IQR] 24.5-55.5 months) and median age at the time of diagnosis was 50.8 years (IQR 46.5-54.5 years). PET-CT scans showed that following the rituximab therapy, the craniocaudal diameter of the RPF mass reduced from 74 mm (IQR 50.5-130 mm) to 52 mm (IQR 35-77 mm; p = .06), and periaortic thickness of the RPF mass reduced from 14 mm (5.5-21.9 mm) to 7 mm (4.5-11 mm; p = .12). The maximum standardized uptake value (based on body weight) of the RPF mass decreased from 5.8 (4.3-9.7) to 3.1 (2.8-5.3) after the therapy (p = .03). The number of patients with hydronephrosis reduced from 11 to 6 following rituximab therapy (p = .04). Before rituximab, nine patients received a median dose of 10 mg (IQR 0-27.5 mg) prednisolone per day. After the rituximab treatment, we discontinued prednisolone treatment for four out of nine patients and reduced the daily dose for the remaining patients. At the time of the final evaluation of the patients, the median prescribed prednisolone dose was 5 mg/day (IQR 2.5-7.5 mg/day; p = .01). CONCLUSION: Our study shows that rituximab may be a favorable treatment option for glucocorticoid-refractory RPF patients with high disease activity on PET-CT scans.

Usefulness of methotrexate in relapsing idiopathic retroperitoneal fibrosis.

OBJECTIVES: Glucocorticoids are the mainstay for treatment of retroperitoneal fibrosis (RPF), a disease characterised by a periaortic proliferation of fibroinflammatory tissue frequently causing urinary obstruction. The therapeutic approach to patients unsuitable for steroid therapy and to relapsing cases is still undefined. METHODS: In this retrospective single-centre study we evaluated 15 patients with RPF who received second-line therapy with methotrexate (MTX) between January 2011 to December 2019. RESULTS: Fourteen out of 15 patients (93%) showed response to MTX. Two patients experienced relapse: one patient when on MTX therapy (28 months), the other, 58 months after MTX was interrupted. Liver toxicity grade 2 was documented in 2 patients and resolved with temporary dosage reduction. One patient stopped MTX autonomously because of nausea. No severe infections were recorded. CONCLUSIONS: In selected patients with RPF who are intolerant or refractory to steroid single therapy, MTX may be considered as useful and safe second-line treatment.

Pilot study of tocilizumab monotherapy for active chronic periaortitis.

OBJECTIVES: To investigate the effectiveness and safety of TCZ (tocilizumab) monotherapy for chronic periaortitis (CP) patients at acute active stage. METHODS: Twelve patients with definite or possible diagnosis of CP were enrolled and received intravenous infusions of TCZ (8 mg/kg) every 4 weeks for at least 3 months. Clinical features, laboratory and imaging findings were recorded at baseline and during the follow-up. The primary endpoint was the rate of partial and complete remission after 3 months TCZ monotherapy and the secondary endpoint was the frequency of treatment related adverse events. RESULTS: Three patients (27.3%) achieved partial remission and seven patients (63.6%) obtained complete remission after 3 months TCZ treatment. The total remission rate achieved 90.9%. All patients reported improvement in clinical symptoms. Inflammatory markers such as erythrocyte sedimentation rate and C reactive protein decreased to normal levels after TCZ treatment. Nine patients (81.8%) showed remarkable shrinkage of perivascular mass greater than or equal to 50% on CT. CONCLUSION: Our study showed that TCZ monotherapy contributed to remarkable clinical and laboratory improvement in CP patients and could be an alternative treatment option for CP.

The Onset of IgG4-related Retroperitoneal Fibrosis under Administration of a TNF Inhibitor in a Rheumatoid Arthritis Patient.

An 80-year-old woman with rheumatoid arthritis during treatment with etanercept, a tumor necrosis factor (TNF) inhibitor, showed swelling of the salivary glands and retroperitoneal fibrosis, which was diagnosed as IgG4-related disease. Although some reports have shown the efficacy of TNF inhibitors for IgG4-related disease or retroperitoneal fibrosis, TNF inhibitors sometimes cause paradoxical reactions like psoriasis, and the mechanisms are considered to involve the upregulation of plasmacytoid dendritic cells and IFN-α, which is also common in patients with IgG4-related disease. This is a case report of IgG4-related retroperitoneal fibrosis with the possibility of a rare paradoxical reaction by a TNF inhibitor.

Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis.

OBJECTIVES: Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects. METHODS: We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics. RESULTS: With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including TH2, TH17 and circulating TFH cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed. CONCLUSIONS: Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.

Idiopathic Retroperitoneal Fibrosis: What Is the Optimal Clinical Approach for Long-Term Preservation of Renal Function?

BACKGROUND: The aim of this study was to investigate the long-term effects of ureteral stenting and the exact timing of stent removal in favor of surgery in patients with idiopathic retroperitoneal fibrosis (IRF). SUMMARY: Medline research terms of "idiopathic retroperitoneal fibrosis" AND " medical therapy" OR "ureteral stenting" OR "surgical treatment" were done. Systematic reviews and observational and clinical studies were analyzed to obtain indication regarding the objective of the study for a narrative review. Ninety-two papers were analyzed. The treatment of IRF includes the monitoring of retroperitoneal fibrotic process spread and the prevention of abdominal organs entrapment. Treatment of ureteral obstruction includes medical therapy and ureteral stenting (US) or percutaneous nephrostomy (PNS) to overcome the worsening of renal function. Up to now, the timing of US or PNS removal is not yet clear, both for the complexity of evaluating the efficacy of the medical therapy and demonstrating the resolution of obstructive nephropathy. Moreover, it is not yet clear if the long-term ureteral stent placement or PNS is able to maintain an efficient renal function. Ureterolysis with a laparoscopic robot-assisted approach is now considered as an ultimate treatment for ureteral obstruction, limiting the progression of kidney impairment and improving the quality of life of patients, although nephrologists are generally abdicant regarding the potential switch toward the surgical approach. KEY MESSAGES: Prospective studies regarding the long-term effects of US on the renal function impairment in patients with IRF should be structured to obtain adequate information on the exact timing for the surgical approach.

Effective therapy of pirfenidone in a patient with idiopathic retroperitoneal fibrosis: report of a case.

Idiopathic retroperitoneal fibrosis (iRPF) is a chronic autoimmune disease characterized by fibroinflammatory tissue surrounding the abdominal aorta and iliac arteries and extending into the retroperitoneum to envelop neighboring structures. Hydronephrosis due to obstruction of ureters is the most common complication of iRPF. Glucocorticoid with or without immunosuppressants or tamoxifen, the mainstay of iRPF treatment, usually brings good response. Nevertheless, in some conditions, the obstruction of ureters remains unresolved with the treatment of all these medications. One of the reasons lies in the innate feature of the fibroinflammatory tissue. The proliferation of fibrosis tissue in addition to inflammation in the mass was associated with insufficient response to immunosuppressive therapies. Pirfenidone, an anti-fibrosis agent, has been successful in treating pulmonary fibrosis and renal fibrosis. Therefore, it is rationale to assume the effectiveness of pirfenidone in the treatment of iRPF. In the current article, we report a 61-year-old Chinese man with iRPF who responded well to pirfenidone.

Clinical significance of soluble interleukin-2 receptor measurement in patients with idiopathic retroperitoneal fibrosis.

BACKGROUND: Idiopathic retroperitoneal fibrosis (iRPF) is a rare chronic fibro-inflammatory disorder of unknown etiology. Activated T-helper cells, which shed soluble interleukin-2 receptor (sIL-2R) into the circulation, may play a pathogenetic role. Hence, measuring sIL-2R may be of value in monitoring disease activity and treatment response in iRPF patients. METHODS: We performed a prospective inception cohort study of 82 patients with untreated (re)active iRPF stratified by elevated (> 623 U/mL) or normal sIL-2R level at baseline and compared disease characteristics among these groups. Baseline and changes in sIL-2R levels following treatment with tamoxifen (TMX) or prednisone (PDN) were analyzed and related to treatment response. RESULTS: Median sIL-2R level was 668 U/mL (IQR 502.8-827.5); 48 patients (59%) had elevated baseline sIL-2R levels. Patients with elevated sIL-2R presented with higher CRP (P = 0.049) and serum creatinine (sCr) levels (P < 0.001) and more often had hydroureteronephrosis (P = 0.01). There was an age and sex adjusted linear association between baseline sIL-2R and both CRP (P = 0.02) and sCr (P < 0.001). Baseline and serial levels of sIL-2R were predictive and concordant, respectively, with clinical response in patients treated with PDN. ROC curve analyses of sIL-2R on a continuous scale and PDN treatment success showed an AUC of 0.84. A serum sIL-2R cut-off value for PDN treatment success of ≤ 703 U/mL was found with a sensitivity of 100% and specificity of 72%. CONCLUSION: Serial measurement of sIL-2R may be of value in monitoring disease activity and PDN treatment response in iRPF patients.

Comprehensive assessment and outcomes of patients with chronic periaortitis.

OBJECTIVES: Chronic periaortitis (CP) is a less known but more frequently diagnosed fibro-inflammatory disorder, but we know little about it and data regarding follow-up and outcome are still very limited. This study aims to identify the clinicopathologic, laboratory, and radiologic features, as well as outcomes of CP patients. METHODS: Patients with CP from HUVAC database were included in the study. CP was diagnosed based on compatible imaging findings and histopathological evaluation (if available), in addition to clinical findings. Demographics, laboratory, clinical, and imaging data were retrospectively reviewed from medical records. RESULTS: A total of 51 (male/female:37/14) patients were included in the study. Median (IQR) age was 63 (53-69) years and follow-up duration was 40 (4-60) months. 32 of the patients were IgG4-related CP. The most common form of CP in our cohort was idiopathic retroperitoneal fibrosis (82%), followed by inflammatory abdominal aortic aneurysms (12%) and peri-aneurysmal retroperitoneal fibrosis (8%). 8 (15.6%) patients had thoracic periaortitis and 16 (31.6%) venous involvement. Cyclophosphamide (CYC) combined with steroids was the most preferred treatment modality (43%), followed by rituximab (RTX) (31.3%). Follow-up imaging was done after a median (IQR) of 7(3-11) months, 30% of the patients were stable and 64.1% showed regression. A total of 18 (35.2%) had been taken off therapy at the last visit. CONCLUSIONS: Idiopathic retroperitoneal fibrosis was the most frequent presentation, whereas 15.6% of patients had thoracic involvement. Venous involvement was also not uncommon. Optimal time for follow-up imaging was determined as 6-9 months. Steroids along with CYC/RTX had a favourable outcome in the treatment of these patients.

Immunoglobulin G4-related retroperitoneal fibrosis.

Some patients diagnosed with idiopathic retroperitoneal fibrosis could be reclassified as IgG4-related disease (IgG4-RD). Classification criteria have not been uniform and prevalence of IgG4-related retroperitoneal fibrosis (IgG4-RPF) is unknown in our region. We aimed to describe IgG4-RPF frequency relying on criteria published recently and comparing clinical, histopathologic and radiologic features with non-IgG4-RPF. From January, 2005 to December, 2020, nineteen adults with histopathologic diagnosis of idiopathic retroperitoneal fibrosis were included in a dynamic retrospective cohort at Hospital Italiano de Buenos Aires. Pathology slides were reviewed and immunohistochemistry was performed and assessed for each case. We used classification criteria described in 2019 American College of Rheumatology/European League Against Rheumatism to identify IgG4-RD cases. Ten of 19 patients met criteria for IgG4-RPF. Median age was similar in two subsets (61 versus 55, p = 0.2) and both had male predominance. Three out of 10 patients (p = 0.2) featured other manifestations of IgG4-RD in the IgG4-RPF group, and periaortic fibrosis was the most significant finding in images (p = 0.01). Corticosteroids were mostly used as therapy, followed by azathioprine and rituximab. Most patients did not receive specific treatment. IgG4-RPF patients had dense lymphocytic infiltrate and 8 out of 10 showed storiform fibrosis (p = 0.02). IgG4+ cells/hpf and IgG4/IgG ratio were significantly higher (p = 0.01). Over half of the patients in our cohort met the criteria of IgG4-RPF. New criteria may harmonize the identification of IgG4-RD. As IgG4-RD may be reversible at initial stages, these findings may lead to early recognition, treatment and integral follow-up.

Muchos pacientes con diagnóstico de fibrosis retroperitoneal idiopática (FRI) pueden ser reclasificados como enfermedad relacionada con IgG4 (ER- IgG4). Los criterios diagnósticos no han sido uniformes y la frecuencia de fibrosis retroperitoneal relacionada con IgG4 en nuestra región es desconocida. El objetivo fue describir la frecuencia de ER-IgG4 en pacientes clasificados como FRI y comparar características clínicas, histopatológicas y de laboratorio con aquellos que no reunían criterios de la enfermedad. Se incluyeron 19 adultos en un estudio de cohorte retrospectiva dinámica con diagnóstico anatomopatológico de FRI, en el Hospital Italiano de Buenos Aires, desde enero de 2005 hasta diciembre de 2020. Se revisaron las biopsias y se realizó inmun ohistoquímica en cada una. Se consideró caso al paciente que reunía los criterios de la American College of Rheumatology/European League Against Rheumatism 2019. Diez pacientes reunieron criterios de ER-IgG4. La mediana de edad fue similar en ambos grupos (61 vs. 55, p = 0.2) y en ambos hubo predominio masculino. Tres de 10 pacientes (p = 0.2) tuvieron otras manifestaciones de ER-IgG4 y la fibrosis periaórtica fue el hallazgo más significativo en los estudios por imágenes (p = 0.01). Los corticoides fueron las drogas más utilizadas seguidos por azatioprina y rituximab, pero la mayoría no recibió tratamiento específico. Todos los pacientes con fibrosis retroperitoneal relacionada con IgG4 presentaron infiltrado linfocitario denso y 8/10 fibrosis estoriforme (p = 0.01), así como las células IgG4+/hpf y ratio IgG4/IgG fueron significativamente mayores (p = 0.01). Más de la mitad de los pacientes con FRI cumplieron criterios de ER-IgG4. Los nuevos criterios diagnósticos podrían contribuir a homogeneizar la identificación de ER-IgG4. Dado que esta enfermedad puede ser reversible en estadios tempranos, estos resultados promueven aumentar el conocimiento de la entidad para tratamiento precoz y seguimiento integral.

An international patient-centred study of retroperitoneal fibrosis.

BACKGROUND: The impact that rare chronic disorders, such as retroperitoneal fibrosis (RPF), can have on the physical and psychological aspects of a patient's health is poorly understood. Patient-related outcome measures and experiences provide a unique opportunity to understand the impact rare chronic disorders have on a patient's life as well as allowing healthcare providers to compare and improve performance. AIM: To understand the physical and psychosocial impact that RPF has upon peoples' lives. DESIGN: An international online questionnaire was therefore created to gain insights into how patients with RPF, a rare fibro-inflammatory condition, viewed their health and experiences. METHODS: An international online questionnaire comprising 62 questions/free text options, was designed in collaboration with two patient advocates and the multi-disciplinary Renal Association Rare Disease Registry (RaDaR) RPF Group the questionnaire was anonymous and freely accessible on a GOOGLE Form online platform for 6 months. RESULTS: A total of 229 patients from 30 countries across 5 continents responded. Four key issues were identified; (i) pain; (ii) therapy-related side effects; (iii) lack of informed doctors/information about their condition and its management; and (iv) psychological burden. Variations in diagnosis and management are highlighted with 55% undergoing a biopsy to reach a diagnosis of RPF; 75% of patients underwent a further interventional procedure with 60% concurrently treated medically. CONCLUSION: This study will guide further development of clinical and academic multi-disciplinary activity and shows the importance of trying to understand the impact of rare chronic disorders on the physical and psychological aspects of a patient's health.

Idiopathic retroperitoneal fibrosis: clinical features, treatment modalities, relapse rate in Greek patients and a review of the literature.

OBJECTIVES: Retroperitoneal fibrosis (RPF) is mostly idiopathic (iRPF); however, it can be secondary to drugs, malignancies, infections, or, as recently recognised, can be part of the IgG4-related diseases. The aim of our study was i) to describe the presenting clinical/laboratory/imaging features and treatment modalities used in patients with iRPF and ii) to evaluate factors potentially associated with disease relapse. METHODS: The medical records of patients diagnosed with iRPF and followed in four tertiary medical units in Athens, Greece from 2000 to 2018 were retrospectively evaluated. RESULTS: Sixty-seven patients with iRPF were included in the study. Seventy-three per cent were males, with a mean age at diagnosis 56.0±9.2 years. Low-back pain (63%) and constitutional symptoms (57%) were the commonest presenting symptoms. Elevated acute-phase reactants (78%), anaemia (43%) and impaired renal function (41%) were the most common laboratory findings. Serum IgG4 at diagnosis was evaluated in 36/67 patients and 36% of them had elevated levels (mean 297.7±166.3mg/dL). Diagnosis was mainly based on abdominal CT and/or MRI. Clinical/laboratory/radiological presentation did not differ between patients with elevated and normal serum IgG4 levels. Steroids were used as first-line treatment in 98%. Relapse occurred in 28.6% after a mean of 43.1±31.8 months. Relapse did not associate to initial clinical/imaging findings or to any treatment used, however patients with increased serum IgG4 had a significantly higher relapse rate (75% vs. 25%, p=0.005). CONCLUSIONS: Relapse occurred in one-fifth of patients independently of the initial clinical/radiographic presentation or treatment used. iRPF patients with baseline elevated serum IgG4 levels have a higher relapse rate.

"Stomach mass" as the first manifestation of IgG4-related disease: a case report.

BACKGROUND: IgG4-related disease mainly manifests as organomegaly and is accompanied by tissue fibrosis (Mimori, Mod Rheumatol 29(2):213, 2019) which is frequently confused with tumour (Dawei et al., J Gastroenterol Hepatol 29(12):1375-8, 2020). There are few reports with of IgG4-related disease with the first clinical manifestation involving the stomach. CASE PRESENTATION: We present the case of 46-year-old male patient with a "stomach tumour" as the first manifestation of IgG4-related disease. Gastroscopy showed a mass in the stomach, however, the pathology result was chronic inflammation with IgG4 positivity. CT scans of abdomen showed that the stomach wall was thick, the head of the pancreas was swollen, and retroperitoneal fibrosis was severe.The serum IgG4 level was 75 g/L (normal range 0.03-2.01 g/L).After treatment with methylprednisolone for one month, the symptoms were greatly relieved. CONCLUSIONS: To reduce the suffering of patients and relieve their financial burden, we should consider the possibility of IgG4-related disease when the initial manifestation is a stomach mass.

Surgical strategy of IgG4-related inflammatory abdominal aortic aneurysm with preoperative steroid therapy: A case report.

Immunoglobulin G4 (IgG4)-related disease, characterized by high serum IgG4 concentrations and IgG4-positive plasma cell infiltration, often presents as an inflammatory aneurysm. We herein report the case of a 78 year-old man, presenting with elevated inflammatory markers and IgG4 concentrations, who was diagnosed with IgG4-related inflammatory abdominal aortic aneurysm with dense perianeurysmal fibrosis. Before the surgical intervention, steroid therapy was administered to resolve his perianeurysmal inflammatory fibrosis. Half a year after the initiation of steroid therapy, there was an improvement in serum inflammatory markers and IgG4 concentrations, and the perianeurysmal fibrosis had regressed. Thus, we performed a surgical intervention including resection of the aneurysm and interposition with a prosthetic graft. Histopathological examination demonstrated few IgG4-positive plasma cells were distributed in the adventitia, which was suspected to be associated with the preoperative steroid therapy. This case study suggests preoperative steroid therapy is a useful therapeutic strategy for IgG4-related abdominal aortic aneurysm because it allows the use of open surgical procedures with reduced surgical risk.