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JAKi offer a potential therapeutic option for mitigating bone loss in RA
Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.
Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.
Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.
Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.
Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0
Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.
Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.
Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.
Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.
Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0
Key clinical point: Janus kinase inhibitors (JAKi) were more potent in inhibiting bone mineral density (BMD) loss compared with other targeted therapies in patients with rheumatoid arthritis (RA), specifically in those with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA.
Major finding: JAKi therapy led to greater gains in bilateral femoral BMD than conventional synthetic disease-modifying antirheumatic drugs (csDMARD; P < .05), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologics, with the improvements in femoral BMD being significant in patients with ACPA-positive RA (P < .01) but not in those with ACPA-negative RA. Similar trends were observed for BMD values at the lumbar spine.
Study details: This retrospective observational study included 362 patients with RA who were treated with JAKi, csDMARD, TNFi, and non-TNFi biologics.
Disclosures: This study was supported by the National Science and Technology Council, Taiwan, and other sources. The authors declared no conflicts of interest.
Source: Chen YW et al. Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis. Clin Rheumatol. 2023 (Sep 2). doi: 10.1007/s10067-023-06735-0
Circulating semaphorin 4A shows potential for predicting treatment failure in RA
Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).
Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).
Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.
Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.
Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3
Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).
Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).
Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.
Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.
Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3
Key clinical point: Circulating semaphorin 4A (SEMA4A) serum levels predicted treatment failure and showed an association with response to therapy in patients with rheumatoid arthritis (RA).
Major finding: Baseline serum levels of SEMA4A > 94 ng/mL predicted the risk for treatment failure defined by the occurrence of flares and treatment escalation (adjusted hazard ratio [aHR] 2.73; 95% CI 1.24-5.96). The baseline SEMA4A serum levels were significantly higher in patients who experienced no or moderate response than in those with a good response (P = .035).
Study details: The data come from a prospective observational routine care study that included two cohorts; the first cohort comprised 101 patients with established RA and the second comprised 40 patients with RA who initiated new therapy due to insufficient disease control.
Disclosures: E Vandebeuque declared receiving grants from the Société Française de Rhumatologie, Paris, and other sources. The authors declared no conflicts of interest.
Source: Avouac J et al. Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment. Sci Rep. 2023;13:14626 (Sep 5). doi: 10.1038/s41598-023-41943-3
Tofacitinib + iguratimod offers choice for dual treat-to-target in RA with usual interstitial pneumonia
Key clinical point: Tofacitinib combined with iguratimod relieves clinical symptoms and results in a higher response rate compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in patients with rheumatoid arthritis with usual interstitial pneumonia (RA-UIP).
Major finding: After 6 months, treatment with tofacitinib + iguratimod vs csDMARD significantly improved forced vital capacity percentage (P = .031) and high-resolution computed tomography fibrosis score (P = .015) and resulted in a higher overall response rate (66.7% vs 35.7%; P = .027), with no patients discontinuing tofacitinib or iguratimod due to side effects or poor efficacy.
Study details:This prospective observational cohort study included 78 patients with RA-UIP who received tofacitinib + iguratimod, csDMARD + iguratimod, or csDMARD.
Disclosures: This study did not declare any specific funding source. The authors declared no conflicts of interest.
Source: Wang S et al. A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia. Front Immunol. 2023;14:1215450 (Aug 23). doi: 10.3389/fimmu.2023.1215450
Key clinical point: Tofacitinib combined with iguratimod relieves clinical symptoms and results in a higher response rate compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in patients with rheumatoid arthritis with usual interstitial pneumonia (RA-UIP).
Major finding: After 6 months, treatment with tofacitinib + iguratimod vs csDMARD significantly improved forced vital capacity percentage (P = .031) and high-resolution computed tomography fibrosis score (P = .015) and resulted in a higher overall response rate (66.7% vs 35.7%; P = .027), with no patients discontinuing tofacitinib or iguratimod due to side effects or poor efficacy.
Study details:This prospective observational cohort study included 78 patients with RA-UIP who received tofacitinib + iguratimod, csDMARD + iguratimod, or csDMARD.
Disclosures: This study did not declare any specific funding source. The authors declared no conflicts of interest.
Source: Wang S et al. A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia. Front Immunol. 2023;14:1215450 (Aug 23). doi: 10.3389/fimmu.2023.1215450
Key clinical point: Tofacitinib combined with iguratimod relieves clinical symptoms and results in a higher response rate compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in patients with rheumatoid arthritis with usual interstitial pneumonia (RA-UIP).
Major finding: After 6 months, treatment with tofacitinib + iguratimod vs csDMARD significantly improved forced vital capacity percentage (P = .031) and high-resolution computed tomography fibrosis score (P = .015) and resulted in a higher overall response rate (66.7% vs 35.7%; P = .027), with no patients discontinuing tofacitinib or iguratimod due to side effects or poor efficacy.
Study details:This prospective observational cohort study included 78 patients with RA-UIP who received tofacitinib + iguratimod, csDMARD + iguratimod, or csDMARD.
Disclosures: This study did not declare any specific funding source. The authors declared no conflicts of interest.
Source: Wang S et al. A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia. Front Immunol. 2023;14:1215450 (Aug 23). doi: 10.3389/fimmu.2023.1215450
Real-world study supports tocilizumab as first-line biologic in DMARD-IR patients with RA
Key clinical point: First-line biologic treatment with tocilizumab significantly reduced disease activity scores and demonstrated a good safety profile in a real-world cohort of patients with rheumatoid arthritis (RA) who had had an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).
Major finding: At 12 months, tocilizumab treatment led to significant reductions in disease activity scores (all P < .001), with 85.5% of patients receiving tocilizumab achieving remission or low disease activity according to the Disease Activity Score of 28 Joints; however, 22.0% of patients switched to other biologic DMARD either due to inefficacy or side effects.
Study details: Findings are from an analysis of 258 patients with RA from the TReasure Registry who were DMARD-IR and received first-line biologic therapy with tocilizumab as monotherapy (n = 80) or in combination with conventional synthetic DMARD (n = 178).
Disclosures: This study was sponsored by Roche Pharmaceuticals, Turkey, and funded by Hacettepe Rheumatology Society, Ankara. Some authors, including the lead author, declared receiving research support, consulting fees, or honoraria from and having other ties with Roche and other sources.
Source: Karadag O et al. Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: Real life experience from the TReasure Registry. Clin Exp Rheumatol. 2023 (Aug 29). doi: 10.55563/clinexprheumatol/2h6ma1
Key clinical point: First-line biologic treatment with tocilizumab significantly reduced disease activity scores and demonstrated a good safety profile in a real-world cohort of patients with rheumatoid arthritis (RA) who had had an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).
Major finding: At 12 months, tocilizumab treatment led to significant reductions in disease activity scores (all P < .001), with 85.5% of patients receiving tocilizumab achieving remission or low disease activity according to the Disease Activity Score of 28 Joints; however, 22.0% of patients switched to other biologic DMARD either due to inefficacy or side effects.
Study details: Findings are from an analysis of 258 patients with RA from the TReasure Registry who were DMARD-IR and received first-line biologic therapy with tocilizumab as monotherapy (n = 80) or in combination with conventional synthetic DMARD (n = 178).
Disclosures: This study was sponsored by Roche Pharmaceuticals, Turkey, and funded by Hacettepe Rheumatology Society, Ankara. Some authors, including the lead author, declared receiving research support, consulting fees, or honoraria from and having other ties with Roche and other sources.
Source: Karadag O et al. Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: Real life experience from the TReasure Registry. Clin Exp Rheumatol. 2023 (Aug 29). doi: 10.55563/clinexprheumatol/2h6ma1
Key clinical point: First-line biologic treatment with tocilizumab significantly reduced disease activity scores and demonstrated a good safety profile in a real-world cohort of patients with rheumatoid arthritis (RA) who had had an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).
Major finding: At 12 months, tocilizumab treatment led to significant reductions in disease activity scores (all P < .001), with 85.5% of patients receiving tocilizumab achieving remission or low disease activity according to the Disease Activity Score of 28 Joints; however, 22.0% of patients switched to other biologic DMARD either due to inefficacy or side effects.
Study details: Findings are from an analysis of 258 patients with RA from the TReasure Registry who were DMARD-IR and received first-line biologic therapy with tocilizumab as monotherapy (n = 80) or in combination with conventional synthetic DMARD (n = 178).
Disclosures: This study was sponsored by Roche Pharmaceuticals, Turkey, and funded by Hacettepe Rheumatology Society, Ankara. Some authors, including the lead author, declared receiving research support, consulting fees, or honoraria from and having other ties with Roche and other sources.
Source: Karadag O et al. Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: Real life experience from the TReasure Registry. Clin Exp Rheumatol. 2023 (Aug 29). doi: 10.55563/clinexprheumatol/2h6ma1
Factors associated with persistent fatigue in early RA
Key clinical point: Patients with early rheumatoid arthritis (RA) presenting with mono- or oligo-arthritis and high perceived disease impact as assessed by Patient Global Assessment (PGA) scores have severe persistent fatigue over time and may benefit from early nonpharmacologic interventions for fatigue.
Major finding: During the 5-year follow-up, the average fatigue score was significantly higher in patients presenting with mono-arthritis (mean difference in fatigue score [β] +4.3 mm; P = .038) and oligo-arthritis (β +4.8 mm; P = .001) vs poly-arthritis at diagnosis, whereas it was significantly lower in patients presenting with poly-arthritis and low PGA scores vs mono- or oligo-arthritis and high PGA scores (β −20 mm; P < .001).
Study details: This study evaluated 1560 and 415 patients with early RA from the Leiden Early Arthritis Cohort and the Treatment in the Rotterdam Early Arthritis Cohort, respectively.
Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Boeren AMP et al. Rheumatoid arthritis presenting with mono- or oligo-arthritis and high VAS remains most fatigued during 5-years follow-up. Rheumatology (Oxford). 2023 (Aug 26). doi: 10.1093/rheumatology/kead429
Key clinical point: Patients with early rheumatoid arthritis (RA) presenting with mono- or oligo-arthritis and high perceived disease impact as assessed by Patient Global Assessment (PGA) scores have severe persistent fatigue over time and may benefit from early nonpharmacologic interventions for fatigue.
Major finding: During the 5-year follow-up, the average fatigue score was significantly higher in patients presenting with mono-arthritis (mean difference in fatigue score [β] +4.3 mm; P = .038) and oligo-arthritis (β +4.8 mm; P = .001) vs poly-arthritis at diagnosis, whereas it was significantly lower in patients presenting with poly-arthritis and low PGA scores vs mono- or oligo-arthritis and high PGA scores (β −20 mm; P < .001).
Study details: This study evaluated 1560 and 415 patients with early RA from the Leiden Early Arthritis Cohort and the Treatment in the Rotterdam Early Arthritis Cohort, respectively.
Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Boeren AMP et al. Rheumatoid arthritis presenting with mono- or oligo-arthritis and high VAS remains most fatigued during 5-years follow-up. Rheumatology (Oxford). 2023 (Aug 26). doi: 10.1093/rheumatology/kead429
Key clinical point: Patients with early rheumatoid arthritis (RA) presenting with mono- or oligo-arthritis and high perceived disease impact as assessed by Patient Global Assessment (PGA) scores have severe persistent fatigue over time and may benefit from early nonpharmacologic interventions for fatigue.
Major finding: During the 5-year follow-up, the average fatigue score was significantly higher in patients presenting with mono-arthritis (mean difference in fatigue score [β] +4.3 mm; P = .038) and oligo-arthritis (β +4.8 mm; P = .001) vs poly-arthritis at diagnosis, whereas it was significantly lower in patients presenting with poly-arthritis and low PGA scores vs mono- or oligo-arthritis and high PGA scores (β −20 mm; P < .001).
Study details: This study evaluated 1560 and 415 patients with early RA from the Leiden Early Arthritis Cohort and the Treatment in the Rotterdam Early Arthritis Cohort, respectively.
Disclosures: This study was supported by the European Research Council and the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Boeren AMP et al. Rheumatoid arthritis presenting with mono- or oligo-arthritis and high VAS remains most fatigued during 5-years follow-up. Rheumatology (Oxford). 2023 (Aug 26). doi: 10.1093/rheumatology/kead429
No effect of initial glucocorticoid bridging on glucocorticoid use over time in RA
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
No effect of initial glucocorticoid bridging on glucocorticoid use over time in RA
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
Key clinical point: In patients with newly diagnosed rheumatoid arthritis (RA), initial glucocorticoid bridging (GB) led to more rapid clinical improvements than non-bridging, without any apparent risk for increased glucocorticoid use after the intended bridging period.
Major finding: The risk of using glucocorticoids at 12 months was higher in the GB vs non-bridging group, but this risk reduced over time and was not significantly different at 18 and 24 months. The cumulative doses did not differ significantly between groups after the planned bridging schedule. Patients in the GB group showed more rapid improvements in the mean Disease Activity Score of 28 Joints during the first 6 months (P < .001).
Study details: This individual patient data meta-analysis combined data from three randomized clinical trials and included 625 patients with newly diagnosed RA who received conventional synthetic disease-modifying antirheumatic drugs with (n = 252) or without (n = 373) initial GB.
Disclosures: This study did not declare any specific funding source. Some authors declared receiving consultancy or speaker honoraria, fees, or grants from or providing expert advice or testimony for or serving as chair for various sources.
Source: van Ouwerkerk L et al. Initial glucocorticoid bridging in rheumatoid arthritis: Does it affect glucocorticoid use over time? Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224270
Tapering TNFi raises disease flare likelihood in patients with RA even in those in remission
Key clinical point: Patients with rheumatoid arthritis (RA) in long-standing remission had a significant risk of experiencing a disease flare if the tumor necrosis factor inhibitor (TNFi) dose is tapered to discontinuation, but most patients regained remission after the original TNFi dose was reinstated.
Major finding: The frequency of disease activity flares during the 12-month follow-up was significantly higher among patients who tapered TNFi to discontinuation vs those who continued with the stable dose (risk difference 58%; P < .0001). However, reinstatement of the initial TNFi dose led to comparable remission rates in both treatment groups.
Study details: Findings are from the phase 4 ARCTIC REWIND trial including 92 patients with RA in sustained remission for ≥ 1 year on stable TNFi therapy and without swollen joints at inclusion, who were randomly assigned to either tapering of their TNFi dose to discontinuation or to a continued stable TNFi dose.
Disclosures: This study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. Some authors declared receiving personal fees or grants from various sources, including the study funders.
Source: Lillegraven S et al. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: A randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224476
Key clinical point: Patients with rheumatoid arthritis (RA) in long-standing remission had a significant risk of experiencing a disease flare if the tumor necrosis factor inhibitor (TNFi) dose is tapered to discontinuation, but most patients regained remission after the original TNFi dose was reinstated.
Major finding: The frequency of disease activity flares during the 12-month follow-up was significantly higher among patients who tapered TNFi to discontinuation vs those who continued with the stable dose (risk difference 58%; P < .0001). However, reinstatement of the initial TNFi dose led to comparable remission rates in both treatment groups.
Study details: Findings are from the phase 4 ARCTIC REWIND trial including 92 patients with RA in sustained remission for ≥ 1 year on stable TNFi therapy and without swollen joints at inclusion, who were randomly assigned to either tapering of their TNFi dose to discontinuation or to a continued stable TNFi dose.
Disclosures: This study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. Some authors declared receiving personal fees or grants from various sources, including the study funders.
Source: Lillegraven S et al. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: A randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224476
Key clinical point: Patients with rheumatoid arthritis (RA) in long-standing remission had a significant risk of experiencing a disease flare if the tumor necrosis factor inhibitor (TNFi) dose is tapered to discontinuation, but most patients regained remission after the original TNFi dose was reinstated.
Major finding: The frequency of disease activity flares during the 12-month follow-up was significantly higher among patients who tapered TNFi to discontinuation vs those who continued with the stable dose (risk difference 58%; P < .0001). However, reinstatement of the initial TNFi dose led to comparable remission rates in both treatment groups.
Study details: Findings are from the phase 4 ARCTIC REWIND trial including 92 patients with RA in sustained remission for ≥ 1 year on stable TNFi therapy and without swollen joints at inclusion, who were randomly assigned to either tapering of their TNFi dose to discontinuation or to a continued stable TNFi dose.
Disclosures: This study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. Some authors declared receiving personal fees or grants from various sources, including the study funders.
Source: Lillegraven S et al. Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: A randomised, open label, non-inferiority trial. Ann Rheum Dis. 2023 (Aug 22). doi: 10.1136/ard-2023-224476
Weight gain and increased BP concerns should not deter low-dose glucocorticoid use in RA
Key clinical point: The administration of low-dose glucocorticoids over 2 years resulted in a modest weight gain of ~1 kg but had no effect on blood pressure (BP) in patients with early and established rheumatoid arthritis (RA).
Major finding: After 2 years, participants in both the low-dose glucocorticoid and control groups gained weight, but the low-dose glucocorticoid group gained an additional 1.1 kg of body weight (P < .001), with no significant between-group differences in the mean arterial pressure (P = .187).
Study details: Findings are from a pooled analysis of five randomized controlled trials including 1112 patients with early and established RA who received low-dose glucocorticoids (≤7.5 mg/day of prednisone equivalent; n = 548) or control treatment (n = 564) over at least 2 years.
Disclosures: This study did not receive any specific funding. Some authors declared receiving investigator fees, grants or contracts, consulting fees, payments or honoraria, or support for attending meetings or travel from or owning stocks or options in various sources.
Source: Palmowski A et al. The effect of low-dose glucocorticoids over two years on weight and blood pressure in rheumatoid arthritis: Individual patient data from five randomized trials. Ann Intern Med. 2023 (Aug 15). doi: 10.7326/M23-0192
Key clinical point: The administration of low-dose glucocorticoids over 2 years resulted in a modest weight gain of ~1 kg but had no effect on blood pressure (BP) in patients with early and established rheumatoid arthritis (RA).
Major finding: After 2 years, participants in both the low-dose glucocorticoid and control groups gained weight, but the low-dose glucocorticoid group gained an additional 1.1 kg of body weight (P < .001), with no significant between-group differences in the mean arterial pressure (P = .187).
Study details: Findings are from a pooled analysis of five randomized controlled trials including 1112 patients with early and established RA who received low-dose glucocorticoids (≤7.5 mg/day of prednisone equivalent; n = 548) or control treatment (n = 564) over at least 2 years.
Disclosures: This study did not receive any specific funding. Some authors declared receiving investigator fees, grants or contracts, consulting fees, payments or honoraria, or support for attending meetings or travel from or owning stocks or options in various sources.
Source: Palmowski A et al. The effect of low-dose glucocorticoids over two years on weight and blood pressure in rheumatoid arthritis: Individual patient data from five randomized trials. Ann Intern Med. 2023 (Aug 15). doi: 10.7326/M23-0192
Key clinical point: The administration of low-dose glucocorticoids over 2 years resulted in a modest weight gain of ~1 kg but had no effect on blood pressure (BP) in patients with early and established rheumatoid arthritis (RA).
Major finding: After 2 years, participants in both the low-dose glucocorticoid and control groups gained weight, but the low-dose glucocorticoid group gained an additional 1.1 kg of body weight (P < .001), with no significant between-group differences in the mean arterial pressure (P = .187).
Study details: Findings are from a pooled analysis of five randomized controlled trials including 1112 patients with early and established RA who received low-dose glucocorticoids (≤7.5 mg/day of prednisone equivalent; n = 548) or control treatment (n = 564) over at least 2 years.
Disclosures: This study did not receive any specific funding. Some authors declared receiving investigator fees, grants or contracts, consulting fees, payments or honoraria, or support for attending meetings or travel from or owning stocks or options in various sources.
Source: Palmowski A et al. The effect of low-dose glucocorticoids over two years on weight and blood pressure in rheumatoid arthritis: Individual patient data from five randomized trials. Ann Intern Med. 2023 (Aug 15). doi: 10.7326/M23-0192
Idiopathic Granulomatous Lobular Mastitis: A Mimicker of Inflammatory Breast Cancer
Idiopathic granulomatous lobular mastitis (IGLM) is a rare, chronic inflammatory breast disease first described in 1972.1 IGLM usually affects women during reproductive years and has similar clinical features to breast cancer.2 Ultrasonography and mammography yield nonspecific results and cannot adequately differentiate between malignancy and inflammation.3 Magnetic resonance imaging (MRI) is known to be more sensitive in detecting lesions in dense breasts; however, it does not differentiate between granulomatous lesions and other disorders.4,5 Histopathology is the gold standard for diagnosis.1-12
Infectious and autoimmune causes of granulomatous mastitis must be excluded before establishing an IGLM diagnosis. The clinical quandary that remains is how to adequately manage the disease. Although there are no defined treatment guidelines, current literature has proposed a multimodal strategy.6,9 In this report, we describe a case of IGLM successfully treated with surgical excision after failed medical therapy.
Case Presentation
A 43-year-old gravida 5, para 4 White woman presented with a 2-week history of right breast tenderness, heaviness, warmth, and redness that was refractory to cephalexin and dicloxacillin. She had no personal or family history of breast cancer; never had breast surgery and breastfed all 4 children.
An examination of the right breast demonstrated erythema and an 8-cm tender mass in the right lower outer quadrant but no skin retraction or dimpling (Figure 1). The mammography, concerning for inflammatory breast cancer, was category BI-RADS 4 and demonstrated a suspicious right axillary lymph node (Figure 2).
A core needle breast biopsy revealed granulomatous mastitis (Figure 3A), without evidence of malignancy. Rheumatology and endocrinology excluded secondary causes of granulomatous mastitis (ie, sarcoidosis, tuberculosis, granulomatosis with polyangiitis, and other autoimmune conditions). A pituitary MRI to assess an elevated serum prolactin level showed no evidence of microadenoma.
After a prolonged course of 8 months of unsuccessful therapy with prednisone and methotrexate, the patient was referred for surgical excision. Culture and special stains (Gram stain, periodic acid-Schiff stain, acid-fast Bacillus culture, Fite stain, and Brown and Benn stain) of the breast tissue were negative for organisms (Figure 3B). Seven months after excision the patient was doing well and had no evidence of recurrence.
Discussion
IGLM is a rare, chronic benign inflammatory breast disease of unknown etiology and more commonly reported in individuals of Mediterranean descent.13 It is believed that hyperprolactinemia causing extravasation of fat and protein during milk letdown leads to lymphocyte and macrophage migration, resulting in a localized autoimmune response in the breast ducts.10,14
There are 2 types of granulomatous mastitis: idiopathic and specific. Infectious, autoimmune, and malignant causes of granulomatous mastitis (ie, tuberculosis, sarcoidosis, Corynebacterium spp, granulomatosis with polyangiitis, systemic lupus erythematosus, Behçet disease, ductal ectasia, or granulomatous reaction in a carcinoma) must be excluded prior to establishing an IGLM diagnosis, as these can be fatal if left untreated.15 The most frequent findings on ultrasound and mammography are hypoechoic masses and focal asymmetric densities, respectively.3,5 MRI has been proposed more for surveillance in patients with chronic IGLM.4,5 Histopathology—featuring lobular noncaseating granulomas with epithelioid histiocytes; and multinucleated giant cells in a background of neutrophils, lymphocytes, plasma cells, and eosinophils—is the gold standard for diagnosing IGLM.1-12
There are currently no universal treatment guidelines and management usually consists of observation, systemic and topical steroids, or surgery.3,13 Topical and injectable steroids have been effective in treating both initial and recurrent IGLM in patients who are unable to be treated with systemic steroids.16-18 Due to reported high recurrence rates with steroid tapers, adjunctive therapy with methotrexate, azathioprine, colchicine, and hydroxychloroquine have been proposed.1,3-6,10-12
Additionally, antibiotics are recommended only in the management of IGLM when microbial co-infection is concerning, such as with Corynebacterium spp.9,11,19-22 Histologically, this bacterium is distinct from IGLM and demonstrates granulomatous, neutrophilic inflammation within cystic spaces.19-21 Wide surgical excision with negative margins is the only definitive treatment to reduce recurrence and expedite recovery time.2,3,7-10 Notably, surgical excision has been associated with poor wound healing and occasional recurrence compared with medication alone.5,11
Although IGLM is normally a benign process, chronic disease has been related (without causality) to infiltrating breast carcinoma.4 A proposed theory for the development of malignancy suggests that chronic inflammation leading to free radical formation can result in cellular dysplasia and cancer.23
Conclusions
Fifty years after its first description, IGLM is still a poorly understood disease. There remains no consensus behind its etiology or management. In our case, we demonstrated a stepwise treatment progression, beginning with medical therapy before proceeding to surgical cure. Given concerns for poor wound healing and postsurgical infections, monitoring the response and recurrence to an initial trial of conservative medical treatment is not unreasonable. Because of possible risk for malignancy with chronic IGLM, patients should not delay surgical excision if their condition remains refractory to medical therapy alone.
1. Garcia-Rodiguez JA, Pattullo A. Idiopathic granulomatous mastitis: a mimicking disease in a pregnant woman: a case report. BMC Res Notes. 2013;6:95. doi.10.1186/1756-0500-6-95
2. Gurleyik G, Aktekin A, Aker F, Karagulle H, Saglamc A. Medical and surgical treatment of idiopathic granulomatous lobular mastitis: a benign inflammatory disease mimicking invasive carcinoma. J Breast Cancer. 2012;15(1):119-123. doi:10.4048/jbc.2012.15.1.119
3. Hovanessian Larsen LJ, Peyvandi B, Klipfel N, Grant E, Iyengar G. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193(2):574-581. doi:10.2214/AJR.08.1528
4. Mazlan L, Suhaimi SN, Jasmin SJ, Latar NH, Adzman S, Muhammad R. Breast carcinoma occurring from chronic granulomatous mastitis. Malays J Med Sci. 2012;19(2):82-85.
5. Patel RA, Strickland P, Sankara IR, Pinkston G, Many W Jr, Rodriguez M. Idiopathic granulomatous mastitis: case reports and review of literature. J Gen Intern Med. 2010;25(3):270-273. doi:10.1007/s11606-009-1207-2
6. Akbulut S, Yilmaz D, Bakir S. Methotrexate in the management of idiopathic granulomatous mastitis: review of 108 published cases and report of four cases. Breast J. 2011;17(6):661-668. doi:10.1111/j.1524-4741.2011.01162.x
7. Ergin AB, Cristofanilli M, Daw H, Tahan G, Gong Y. Recurrent granulomatous mastitis mimicking inflammatory breast cancer. BMJ Case Rep. 2011;2011:bcr0720103156. doi:10.1136/bcr.07.2010.3156
8. Hladik M, Schoeller T, Ensat F, Wechselberger G. Idiopathic granulomatous mastitis: successful treatment by mastectomy and immediate breast reconstruction. J Plast Reconstr Aesthet Surg. 2011;64(12):1604-1607. doi:10.1016/j.bjps.2011.07.01
9. Hur SM, Cho DH, Lee SK, et al. Experience of treatment of patients with granulomatous lobular mastitis. J Korean Surg Soc. 2013;85(1):1-6. doi:10.4174/jkss.2013.85.1.
10. Kayahan M, Kadioglu H, Muslumanoglu M. Management of patients with granulomatous mastitis: analysis of 31 cases. Breast Care (Basel). 2012;7(3):226-230. doi:10.1159/000337758
11. Neel A, Hello M, Cottereau A, et al. Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study. QJM. 2013;106(5):433-441. doi:10.1093/qjmed/hct040
12. Seo HR, Na KY, Yim HE, et al. Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis. J Breast Cancer. 2012;15(1):111-118. doi:10.4048/jbc.2012.15.1.111
13. Martinez-Ramos D, Simon-Monterde L, Suelves-Piqueres C, et al. Idiopathic granulomatous mastitis: a systematic review of 3060 patients. Breast J. 2019;25(6):1245-1250. doi:10.1111/tbj.13446
14. Lin CH, Hsu CW, Tsao TY, Chou J. Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia. Diagn Pathol. 2012;7:2. doi:10.1186/1746-1596-7-2
15. Goulabchand R, Hafidi A, Van de Perre P, et al. Mastitis in autoimmune diseases: review of the literature, diagnostic pathway, and pathophysiological key players. J Clin Med. 2020;9(4):958. doi:10.3390/jcm9040958
16. Altintoprak F. Topical steroids to treat granulomatous mastitis: a case report. Korean J Intern Med. 2011;26(3):356-359. doi:10.3904/kjim.2011.26.3.356
17. Tang A, Dominguez DA, Edquilang JK, et al. Granulomatous mastitis: comparison of novel treatment of steroid injection and current management. J Surg Res. 2020;254:300-305. doi:10.1016/j.jss.2020.04.018
18. Toktas O, Toprak N. Treatment results of intralesional steroid injection and topical steroid administration in pregnant women with idiopathic granulomatous mastitis. Eur J Breast Health. 2021;17(3):283-287. doi:10.4274/ejbh.galenos.2021.2021-2-4
19. Bercot B, Kannengiesser C, Oudin C, et al. First description of NOD2 variant associated with defective neutrophil responses in a woman with granulomatous mastitis related to corynebacteria. J Clin Microbiol. 2009;47(9):3034-3037. doi:10.1128/JCM.00561-09
20. Renshaw AA, Derhagopian RP, Gould EW. Cystic neutrophilic granulomatous mastitis: an underappreciated pattern strongly associated with gram-positive bacilli. Am J Clin Pathol. 2011;136(3):424-427. doi:10.1309/AJCP1W9JBRYOQSNZ
21. Stary CM, Lee YS, Balfour J. Idiopathic granulomatous mastitis associated with corynebacterium sp. Infection. Hawaii Med J. 2011;70(5):99-101.
22. Taylor GB, Paviour SD, Musaad S, Jones WO, Holland DJ. A clinicopathological review of 34 cases of inflammatory breast disease showing an association between corynebacteria infection and granulomatous mastitis. Pathology. 2003;35(2):109-119.
23. Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3-4):123-130.
Idiopathic granulomatous lobular mastitis (IGLM) is a rare, chronic inflammatory breast disease first described in 1972.1 IGLM usually affects women during reproductive years and has similar clinical features to breast cancer.2 Ultrasonography and mammography yield nonspecific results and cannot adequately differentiate between malignancy and inflammation.3 Magnetic resonance imaging (MRI) is known to be more sensitive in detecting lesions in dense breasts; however, it does not differentiate between granulomatous lesions and other disorders.4,5 Histopathology is the gold standard for diagnosis.1-12
Infectious and autoimmune causes of granulomatous mastitis must be excluded before establishing an IGLM diagnosis. The clinical quandary that remains is how to adequately manage the disease. Although there are no defined treatment guidelines, current literature has proposed a multimodal strategy.6,9 In this report, we describe a case of IGLM successfully treated with surgical excision after failed medical therapy.
Case Presentation
A 43-year-old gravida 5, para 4 White woman presented with a 2-week history of right breast tenderness, heaviness, warmth, and redness that was refractory to cephalexin and dicloxacillin. She had no personal or family history of breast cancer; never had breast surgery and breastfed all 4 children.
An examination of the right breast demonstrated erythema and an 8-cm tender mass in the right lower outer quadrant but no skin retraction or dimpling (Figure 1). The mammography, concerning for inflammatory breast cancer, was category BI-RADS 4 and demonstrated a suspicious right axillary lymph node (Figure 2).
A core needle breast biopsy revealed granulomatous mastitis (Figure 3A), without evidence of malignancy. Rheumatology and endocrinology excluded secondary causes of granulomatous mastitis (ie, sarcoidosis, tuberculosis, granulomatosis with polyangiitis, and other autoimmune conditions). A pituitary MRI to assess an elevated serum prolactin level showed no evidence of microadenoma.
After a prolonged course of 8 months of unsuccessful therapy with prednisone and methotrexate, the patient was referred for surgical excision. Culture and special stains (Gram stain, periodic acid-Schiff stain, acid-fast Bacillus culture, Fite stain, and Brown and Benn stain) of the breast tissue were negative for organisms (Figure 3B). Seven months after excision the patient was doing well and had no evidence of recurrence.
Discussion
IGLM is a rare, chronic benign inflammatory breast disease of unknown etiology and more commonly reported in individuals of Mediterranean descent.13 It is believed that hyperprolactinemia causing extravasation of fat and protein during milk letdown leads to lymphocyte and macrophage migration, resulting in a localized autoimmune response in the breast ducts.10,14
There are 2 types of granulomatous mastitis: idiopathic and specific. Infectious, autoimmune, and malignant causes of granulomatous mastitis (ie, tuberculosis, sarcoidosis, Corynebacterium spp, granulomatosis with polyangiitis, systemic lupus erythematosus, Behçet disease, ductal ectasia, or granulomatous reaction in a carcinoma) must be excluded prior to establishing an IGLM diagnosis, as these can be fatal if left untreated.15 The most frequent findings on ultrasound and mammography are hypoechoic masses and focal asymmetric densities, respectively.3,5 MRI has been proposed more for surveillance in patients with chronic IGLM.4,5 Histopathology—featuring lobular noncaseating granulomas with epithelioid histiocytes; and multinucleated giant cells in a background of neutrophils, lymphocytes, plasma cells, and eosinophils—is the gold standard for diagnosing IGLM.1-12
There are currently no universal treatment guidelines and management usually consists of observation, systemic and topical steroids, or surgery.3,13 Topical and injectable steroids have been effective in treating both initial and recurrent IGLM in patients who are unable to be treated with systemic steroids.16-18 Due to reported high recurrence rates with steroid tapers, adjunctive therapy with methotrexate, azathioprine, colchicine, and hydroxychloroquine have been proposed.1,3-6,10-12
Additionally, antibiotics are recommended only in the management of IGLM when microbial co-infection is concerning, such as with Corynebacterium spp.9,11,19-22 Histologically, this bacterium is distinct from IGLM and demonstrates granulomatous, neutrophilic inflammation within cystic spaces.19-21 Wide surgical excision with negative margins is the only definitive treatment to reduce recurrence and expedite recovery time.2,3,7-10 Notably, surgical excision has been associated with poor wound healing and occasional recurrence compared with medication alone.5,11
Although IGLM is normally a benign process, chronic disease has been related (without causality) to infiltrating breast carcinoma.4 A proposed theory for the development of malignancy suggests that chronic inflammation leading to free radical formation can result in cellular dysplasia and cancer.23
Conclusions
Fifty years after its first description, IGLM is still a poorly understood disease. There remains no consensus behind its etiology or management. In our case, we demonstrated a stepwise treatment progression, beginning with medical therapy before proceeding to surgical cure. Given concerns for poor wound healing and postsurgical infections, monitoring the response and recurrence to an initial trial of conservative medical treatment is not unreasonable. Because of possible risk for malignancy with chronic IGLM, patients should not delay surgical excision if their condition remains refractory to medical therapy alone.
Idiopathic granulomatous lobular mastitis (IGLM) is a rare, chronic inflammatory breast disease first described in 1972.1 IGLM usually affects women during reproductive years and has similar clinical features to breast cancer.2 Ultrasonography and mammography yield nonspecific results and cannot adequately differentiate between malignancy and inflammation.3 Magnetic resonance imaging (MRI) is known to be more sensitive in detecting lesions in dense breasts; however, it does not differentiate between granulomatous lesions and other disorders.4,5 Histopathology is the gold standard for diagnosis.1-12
Infectious and autoimmune causes of granulomatous mastitis must be excluded before establishing an IGLM diagnosis. The clinical quandary that remains is how to adequately manage the disease. Although there are no defined treatment guidelines, current literature has proposed a multimodal strategy.6,9 In this report, we describe a case of IGLM successfully treated with surgical excision after failed medical therapy.
Case Presentation
A 43-year-old gravida 5, para 4 White woman presented with a 2-week history of right breast tenderness, heaviness, warmth, and redness that was refractory to cephalexin and dicloxacillin. She had no personal or family history of breast cancer; never had breast surgery and breastfed all 4 children.
An examination of the right breast demonstrated erythema and an 8-cm tender mass in the right lower outer quadrant but no skin retraction or dimpling (Figure 1). The mammography, concerning for inflammatory breast cancer, was category BI-RADS 4 and demonstrated a suspicious right axillary lymph node (Figure 2).
A core needle breast biopsy revealed granulomatous mastitis (Figure 3A), without evidence of malignancy. Rheumatology and endocrinology excluded secondary causes of granulomatous mastitis (ie, sarcoidosis, tuberculosis, granulomatosis with polyangiitis, and other autoimmune conditions). A pituitary MRI to assess an elevated serum prolactin level showed no evidence of microadenoma.
After a prolonged course of 8 months of unsuccessful therapy with prednisone and methotrexate, the patient was referred for surgical excision. Culture and special stains (Gram stain, periodic acid-Schiff stain, acid-fast Bacillus culture, Fite stain, and Brown and Benn stain) of the breast tissue were negative for organisms (Figure 3B). Seven months after excision the patient was doing well and had no evidence of recurrence.
Discussion
IGLM is a rare, chronic benign inflammatory breast disease of unknown etiology and more commonly reported in individuals of Mediterranean descent.13 It is believed that hyperprolactinemia causing extravasation of fat and protein during milk letdown leads to lymphocyte and macrophage migration, resulting in a localized autoimmune response in the breast ducts.10,14
There are 2 types of granulomatous mastitis: idiopathic and specific. Infectious, autoimmune, and malignant causes of granulomatous mastitis (ie, tuberculosis, sarcoidosis, Corynebacterium spp, granulomatosis with polyangiitis, systemic lupus erythematosus, Behçet disease, ductal ectasia, or granulomatous reaction in a carcinoma) must be excluded prior to establishing an IGLM diagnosis, as these can be fatal if left untreated.15 The most frequent findings on ultrasound and mammography are hypoechoic masses and focal asymmetric densities, respectively.3,5 MRI has been proposed more for surveillance in patients with chronic IGLM.4,5 Histopathology—featuring lobular noncaseating granulomas with epithelioid histiocytes; and multinucleated giant cells in a background of neutrophils, lymphocytes, plasma cells, and eosinophils—is the gold standard for diagnosing IGLM.1-12
There are currently no universal treatment guidelines and management usually consists of observation, systemic and topical steroids, or surgery.3,13 Topical and injectable steroids have been effective in treating both initial and recurrent IGLM in patients who are unable to be treated with systemic steroids.16-18 Due to reported high recurrence rates with steroid tapers, adjunctive therapy with methotrexate, azathioprine, colchicine, and hydroxychloroquine have been proposed.1,3-6,10-12
Additionally, antibiotics are recommended only in the management of IGLM when microbial co-infection is concerning, such as with Corynebacterium spp.9,11,19-22 Histologically, this bacterium is distinct from IGLM and demonstrates granulomatous, neutrophilic inflammation within cystic spaces.19-21 Wide surgical excision with negative margins is the only definitive treatment to reduce recurrence and expedite recovery time.2,3,7-10 Notably, surgical excision has been associated with poor wound healing and occasional recurrence compared with medication alone.5,11
Although IGLM is normally a benign process, chronic disease has been related (without causality) to infiltrating breast carcinoma.4 A proposed theory for the development of malignancy suggests that chronic inflammation leading to free radical formation can result in cellular dysplasia and cancer.23
Conclusions
Fifty years after its first description, IGLM is still a poorly understood disease. There remains no consensus behind its etiology or management. In our case, we demonstrated a stepwise treatment progression, beginning with medical therapy before proceeding to surgical cure. Given concerns for poor wound healing and postsurgical infections, monitoring the response and recurrence to an initial trial of conservative medical treatment is not unreasonable. Because of possible risk for malignancy with chronic IGLM, patients should not delay surgical excision if their condition remains refractory to medical therapy alone.
1. Garcia-Rodiguez JA, Pattullo A. Idiopathic granulomatous mastitis: a mimicking disease in a pregnant woman: a case report. BMC Res Notes. 2013;6:95. doi.10.1186/1756-0500-6-95
2. Gurleyik G, Aktekin A, Aker F, Karagulle H, Saglamc A. Medical and surgical treatment of idiopathic granulomatous lobular mastitis: a benign inflammatory disease mimicking invasive carcinoma. J Breast Cancer. 2012;15(1):119-123. doi:10.4048/jbc.2012.15.1.119
3. Hovanessian Larsen LJ, Peyvandi B, Klipfel N, Grant E, Iyengar G. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193(2):574-581. doi:10.2214/AJR.08.1528
4. Mazlan L, Suhaimi SN, Jasmin SJ, Latar NH, Adzman S, Muhammad R. Breast carcinoma occurring from chronic granulomatous mastitis. Malays J Med Sci. 2012;19(2):82-85.
5. Patel RA, Strickland P, Sankara IR, Pinkston G, Many W Jr, Rodriguez M. Idiopathic granulomatous mastitis: case reports and review of literature. J Gen Intern Med. 2010;25(3):270-273. doi:10.1007/s11606-009-1207-2
6. Akbulut S, Yilmaz D, Bakir S. Methotrexate in the management of idiopathic granulomatous mastitis: review of 108 published cases and report of four cases. Breast J. 2011;17(6):661-668. doi:10.1111/j.1524-4741.2011.01162.x
7. Ergin AB, Cristofanilli M, Daw H, Tahan G, Gong Y. Recurrent granulomatous mastitis mimicking inflammatory breast cancer. BMJ Case Rep. 2011;2011:bcr0720103156. doi:10.1136/bcr.07.2010.3156
8. Hladik M, Schoeller T, Ensat F, Wechselberger G. Idiopathic granulomatous mastitis: successful treatment by mastectomy and immediate breast reconstruction. J Plast Reconstr Aesthet Surg. 2011;64(12):1604-1607. doi:10.1016/j.bjps.2011.07.01
9. Hur SM, Cho DH, Lee SK, et al. Experience of treatment of patients with granulomatous lobular mastitis. J Korean Surg Soc. 2013;85(1):1-6. doi:10.4174/jkss.2013.85.1.
10. Kayahan M, Kadioglu H, Muslumanoglu M. Management of patients with granulomatous mastitis: analysis of 31 cases. Breast Care (Basel). 2012;7(3):226-230. doi:10.1159/000337758
11. Neel A, Hello M, Cottereau A, et al. Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study. QJM. 2013;106(5):433-441. doi:10.1093/qjmed/hct040
12. Seo HR, Na KY, Yim HE, et al. Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis. J Breast Cancer. 2012;15(1):111-118. doi:10.4048/jbc.2012.15.1.111
13. Martinez-Ramos D, Simon-Monterde L, Suelves-Piqueres C, et al. Idiopathic granulomatous mastitis: a systematic review of 3060 patients. Breast J. 2019;25(6):1245-1250. doi:10.1111/tbj.13446
14. Lin CH, Hsu CW, Tsao TY, Chou J. Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia. Diagn Pathol. 2012;7:2. doi:10.1186/1746-1596-7-2
15. Goulabchand R, Hafidi A, Van de Perre P, et al. Mastitis in autoimmune diseases: review of the literature, diagnostic pathway, and pathophysiological key players. J Clin Med. 2020;9(4):958. doi:10.3390/jcm9040958
16. Altintoprak F. Topical steroids to treat granulomatous mastitis: a case report. Korean J Intern Med. 2011;26(3):356-359. doi:10.3904/kjim.2011.26.3.356
17. Tang A, Dominguez DA, Edquilang JK, et al. Granulomatous mastitis: comparison of novel treatment of steroid injection and current management. J Surg Res. 2020;254:300-305. doi:10.1016/j.jss.2020.04.018
18. Toktas O, Toprak N. Treatment results of intralesional steroid injection and topical steroid administration in pregnant women with idiopathic granulomatous mastitis. Eur J Breast Health. 2021;17(3):283-287. doi:10.4274/ejbh.galenos.2021.2021-2-4
19. Bercot B, Kannengiesser C, Oudin C, et al. First description of NOD2 variant associated with defective neutrophil responses in a woman with granulomatous mastitis related to corynebacteria. J Clin Microbiol. 2009;47(9):3034-3037. doi:10.1128/JCM.00561-09
20. Renshaw AA, Derhagopian RP, Gould EW. Cystic neutrophilic granulomatous mastitis: an underappreciated pattern strongly associated with gram-positive bacilli. Am J Clin Pathol. 2011;136(3):424-427. doi:10.1309/AJCP1W9JBRYOQSNZ
21. Stary CM, Lee YS, Balfour J. Idiopathic granulomatous mastitis associated with corynebacterium sp. Infection. Hawaii Med J. 2011;70(5):99-101.
22. Taylor GB, Paviour SD, Musaad S, Jones WO, Holland DJ. A clinicopathological review of 34 cases of inflammatory breast disease showing an association between corynebacteria infection and granulomatous mastitis. Pathology. 2003;35(2):109-119.
23. Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3-4):123-130.
1. Garcia-Rodiguez JA, Pattullo A. Idiopathic granulomatous mastitis: a mimicking disease in a pregnant woman: a case report. BMC Res Notes. 2013;6:95. doi.10.1186/1756-0500-6-95
2. Gurleyik G, Aktekin A, Aker F, Karagulle H, Saglamc A. Medical and surgical treatment of idiopathic granulomatous lobular mastitis: a benign inflammatory disease mimicking invasive carcinoma. J Breast Cancer. 2012;15(1):119-123. doi:10.4048/jbc.2012.15.1.119
3. Hovanessian Larsen LJ, Peyvandi B, Klipfel N, Grant E, Iyengar G. Granulomatous lobular mastitis: imaging, diagnosis, and treatment. AJR Am J Roentgenol. 2009;193(2):574-581. doi:10.2214/AJR.08.1528
4. Mazlan L, Suhaimi SN, Jasmin SJ, Latar NH, Adzman S, Muhammad R. Breast carcinoma occurring from chronic granulomatous mastitis. Malays J Med Sci. 2012;19(2):82-85.
5. Patel RA, Strickland P, Sankara IR, Pinkston G, Many W Jr, Rodriguez M. Idiopathic granulomatous mastitis: case reports and review of literature. J Gen Intern Med. 2010;25(3):270-273. doi:10.1007/s11606-009-1207-2
6. Akbulut S, Yilmaz D, Bakir S. Methotrexate in the management of idiopathic granulomatous mastitis: review of 108 published cases and report of four cases. Breast J. 2011;17(6):661-668. doi:10.1111/j.1524-4741.2011.01162.x
7. Ergin AB, Cristofanilli M, Daw H, Tahan G, Gong Y. Recurrent granulomatous mastitis mimicking inflammatory breast cancer. BMJ Case Rep. 2011;2011:bcr0720103156. doi:10.1136/bcr.07.2010.3156
8. Hladik M, Schoeller T, Ensat F, Wechselberger G. Idiopathic granulomatous mastitis: successful treatment by mastectomy and immediate breast reconstruction. J Plast Reconstr Aesthet Surg. 2011;64(12):1604-1607. doi:10.1016/j.bjps.2011.07.01
9. Hur SM, Cho DH, Lee SK, et al. Experience of treatment of patients with granulomatous lobular mastitis. J Korean Surg Soc. 2013;85(1):1-6. doi:10.4174/jkss.2013.85.1.
10. Kayahan M, Kadioglu H, Muslumanoglu M. Management of patients with granulomatous mastitis: analysis of 31 cases. Breast Care (Basel). 2012;7(3):226-230. doi:10.1159/000337758
11. Neel A, Hello M, Cottereau A, et al. Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study. QJM. 2013;106(5):433-441. doi:10.1093/qjmed/hct040
12. Seo HR, Na KY, Yim HE, et al. Differential diagnosis in idiopathic granulomatous mastitis and tuberculous mastitis. J Breast Cancer. 2012;15(1):111-118. doi:10.4048/jbc.2012.15.1.111
13. Martinez-Ramos D, Simon-Monterde L, Suelves-Piqueres C, et al. Idiopathic granulomatous mastitis: a systematic review of 3060 patients. Breast J. 2019;25(6):1245-1250. doi:10.1111/tbj.13446
14. Lin CH, Hsu CW, Tsao TY, Chou J. Idiopathic granulomatous mastitis associated with risperidone-induced hyperprolactinemia. Diagn Pathol. 2012;7:2. doi:10.1186/1746-1596-7-2
15. Goulabchand R, Hafidi A, Van de Perre P, et al. Mastitis in autoimmune diseases: review of the literature, diagnostic pathway, and pathophysiological key players. J Clin Med. 2020;9(4):958. doi:10.3390/jcm9040958
16. Altintoprak F. Topical steroids to treat granulomatous mastitis: a case report. Korean J Intern Med. 2011;26(3):356-359. doi:10.3904/kjim.2011.26.3.356
17. Tang A, Dominguez DA, Edquilang JK, et al. Granulomatous mastitis: comparison of novel treatment of steroid injection and current management. J Surg Res. 2020;254:300-305. doi:10.1016/j.jss.2020.04.018
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