Ozone therapy restores immune dysfunction in refractory idiopathic granulomatous mastitis as a novel potential therapeutic approach.

Immunological dysfunction has been suggested to play a major role in the pathogenesis of idiopathic granulomatous mastitis (IGM). We recently showed that ozone therapy was effective in patients with steroid-resistant IGM. This study assessed alterations in intracellular cytokine expression patterns in different T-lymphocyte subsets after ozone therapy in refractory IGM. Peripheral blood T lymphocyte subsets (CD8+ , CD4+ , CD4+ CD25+ CD127- ) were analyzed via flow-cytometry for intracellular cytokine expressions IFN-γ, TNF-α, IL-10, and TGF-ß before and after completion of 4-month systemic ozone therapy. Ozone therapy significantly increased the CD4+ IFN-γ+ (p = 0.032), CD4+ TNF-α+ (p = 0.028), and the CD8+ TNF-α+ (p = 0.012) T cells. In contrast, significant decreases in CD4+ IL-10+ (p = 0.047) and CD8+ IL-10+ T cells (p = 0.022) and CD4+ CD25+ CD127-//low Treg cells secreting TGF-ß (p = 0.005) were found after ozone therapy. When patients were analyzed according to the response to ozone therapy, patients with a complete remission were more likely to have increased CD3- CD16+ CD56+ natural killer cells (p = 0.0027) and decreased CD19+ B lymphocytes (p = 0.046) following ozone therapy. Our results suggest that ozone therapy stimulated a T-helper-1 response associated with IFN-γ production and downregulation of TGF-ß expression in CD4+ CD25+ CD127- Treg cells. These alterations in the immune system following ozone therapy can improve wound healing and restore immune dysfunction in patients with refractory IGM.

Mastitis granulomatosa idiopática: Caso clínico y revisión literaria / Idiopathic granulomatose mastitis: Case report and literary review

Se describe el caso clínico de una paciente con diagnóstico histológico de mastitis granulomatosa idiopática, enfermedad poco frecuente en la que se utilizan inmunosupresores como tratamiento descripto y puede confundirse con otras entidades atendidas en la especialidad. Se describe el caso y se realiza una revisión de la literatura.

The clinical case of a patient with a histological diagnosis of idiopathic granulomatous mastitis is described, a rare disease in which immunosuppressants are used as the described treatment and can be confused with other entities treated in the specialty. The case is described and a literature review is carried out.

A rheumatologic approach to granulomatous mastitis: A case series and review of the literature.

AIM: Idiopathic granulomatous mastitis (IGM) is an enigmatic inflammatory breast disorder. IGM responds to immunomodulatory treatment and may be associated with systemic manifestations such as arthritis and erythema nodosum. These patients are increasingly referred to rheumatologists for management, but IGM is rarely discussed in the rheumatology literature. The objective of this report is to familiarize rheumatologists with the treatment and systemic manifestations of IGM. We report here a case series of IGM at our institution, and a literature review of IGM treated with methotrexate (MTX). METHOD: Patients with IGM at our institution were identified and described using a retrospective chart review. A literature review of PubMed and Google Scholar identified studies of IGM patients treated with MTX. RESULTS: We identified 28 IGM patients at our institution. Inflammatory arthritis/arthralgia were present in four patients (14%), and five patients (18%) had erythema nodosum. Patients treated with MTX had the highest rates of relapse-free remission; relapse-free remission occurred in four of the five (80%) MTX-treated patients, compared with 5 of 12 (42%) patients treated with steroids alone, and two or three (66%) patients treated with steroids and surgery. In the literature review, 116 patients treated with MTX were identified, and the rate of relapse-free remission ranged from 58% to 100%. Arthritis/arthralgia and erythema nodosum were more common at our institution than reported in the literature. CONCLUSION: Methotrexate is a promising treatment for IGM. Arthritis/arthralgias and erythema nodosum may be under-recognized when IGM patients are managed outside rheumatology. Prospective studies are needed to characterize clinical features and optimum treatment of IGM.

What are the new findings with regard to the mysterious disease idiopathic granulomatous mastitis?

PURPOSE: To review the demographic and clinical features and the success rates of treatment approaches for idiopathic granulomatous mastitis (IGM). METHODS: A total of 134 patients diagnosed with IGM pathologically and treated by a single breast surgeon were retrospectively analyzed. RESULTS: The time between the occurrence of symptoms and the last delivery was < 24 months in 25 (23.1%), 24-48 months in 51 (38.1%), and > 48 months in 52 (38.8%). The difference was statistically significant (p = 0.002). Although there was no significant difference, seasonal fluctuations were noticed, with the incidence being slightly higher during late spring and summer. Bilateral disease was present in 10 (7.5%) patients. Seven patients (5.2%) had erythema nodosum. The treatment approaches were conservative in 42, surgical procedures in 48, steroid treatment in 18, and surgical procedure + steroid treatment in 24. The median recovery time with conservative approaches was lower than that with surgical procedure + steroid treatment (p < 0.0001). Recurrence developed in 10 patients (7.7%). CONCLUSION: Clinical differences were detected among the patients with IGM, and classification of patients by severity is needed to plan the optimal treatment approach. Seasonal fluctuations suggest the possibility of an immunological disease rather than a surgical disease.

Human leukocyte antigens class I and II in patients with idiopathic granulomatous mastitis.

BACKGROUND: To determine the distribution of human leukocyte antigens (HLA) in patients with idiopathic granulomatous mastitis (IGM). METHODS: The study included 48 patients diagnosed with IGM and 50 controls consisting of healthy donor candidates. RESULTS: The frequencies of HLA-A*10, HLA-A*2403, HLA-B*18 and HLA-DR*17 antigens were significantly higher in the patient group than control group (p = 0.012, p = 0.012, p = 0.0001 and p = 0.005, respectively). However, the frequencies of HLA-A*29, HLA-B*14 and HLA-DR*1 were lower in the patient group than control group (p = 0.027, p = 0.013 and p = 0.015, respectively). When patients without/with relapse were compared, there was a significant difference in HLA-A*3 (p = 0.048) and HLA-A*32 (p = 0.011). Also, the patients with relapse and control group were compared in respects of HLA-A*10 (p = 0.0006), HLA-A*24 (p = 0.035), HLA-A*32 (p = 0.011), HLA-B*18 (p = 0.035), HLA-B*103 (p = 0.035) and HLA-DR*17 (p = 0.006). CONCLUSION: These findings may help to explain etiopathogenesis but still, further studies on this subject with more patients in different geographic regions are needed.

Granulomatous Mastitis in a Hispanic Woman.

A 33-year-old mother of 2 healthy children presented with bilateral recurrent breast infections despite successful treatment of each episode of an infection. With a negative rheumatologic medical history as well as a negative review of systems, she continued to have these infections frequently. Hence, a breast biopsy was performed after the treatment with a course of antimicrobials, which revealed changes suggestive of granulomatous mastitis. She was started on methotrexate (MTX) with a good response. But, due to persistent nodularity, corticosteroids were added to the regimen with MTX dose escalation. Patient remained disease free thereafter without any adverse effects.

Two Cases of Granulomatous Mastitis Caused by Corynebacterium kroppenstedtii Infection in Nulliparous Young Women with Hyperprolactinemia.

Recently, an association between granulomatous mastitis and local infection with Corynebacterium (C.) kroppenstedtii has been suggested. We herein report two cases of granulomatous mastitis resulting from C. kroppenstedtii infection in nulliparous young women with hyperprolactinemia. Both cases involved nulliparous patients with drug-induced hyperprolactinemia, and both individuals received incision and drainage, after which the pus was sent to our laboratory. Corynebacterium spp. grew on blood agar, and 16S rRNA gene sequencing identified the pathogen as C. kroppenstedtii. In conclusion, lactational changes caused by drug-induced hyperprolactinemia may increase the risk of granulomatous mastitis after C. kroppenstedtii infection.

Inflammatory diseases of the non-lactating female breasts.

UNLABELLED: Chronic inflammatory diseases of the non-lactating breasts cause considerable difficulty in diagnosis and treatment. There is a spectrum of aetiological factors ranging from infection to autoimmune disorders. The disease causes considerable morbidity and psychological distress in relatively young females. The study aimed to analyse the spectrum of chronic disease and to formulate a treatment protocol. METHOD: Female patients with histological confirmation of inflammatory disease of the breast in the non-lactational phase were included in the study. The patients were categorized based on histological findings supplemented with immunohistochemical staining with CD3 and CD20 antibodies. RESULT: Out of 50 patients included in the study, 38 patients (76%) were diagnosed as idiopathic granulomatous mastitis (IGM) and 12 (24%) patients as periductal mastitis (PD). The possible aetiology of IGM was localized autoimmunity as evidenced by the infiltration of CD3 positive T lymphocyte. Systemic prednisolone was given for 6 months and 95.6% patients were disease-free after 24months. Out of 15 patients who did not receive prednisolone, only 2 patients were disease-free after 24 months (p = .003). CONCLUSION: Idiopathic granulomatous mastitis is an uncommon inflammatory disease of the non-lactating breast. The combination of limited surgical treatment and systemic prednisolone given for 6 months effectively controls the disease as well as prevents recurrence.

Idiopathic granulomatous mastitis: an autoimmune disease?

PURPOSE: This study aimed to investigate the autoimmune basis of idiopathic granulomatous mastitis (IGM) by determining the anti-nuclear antibody (ANA) and extractable nuclear antigen (ENA) levels of patients diagnosed with IGM. MATERIAL AND METHODS: Twenty-six IGM patients were evaluated. Serum samples were analyzed for autoantibodies by indirect immunofluorescence (IIF) using a substrate kit that induced fluorescein-conjugated goat antibodies to human immunoglobulin G (IgG). IIF patterns were read at serum dilutions of 1 : 40 and 1 : 100 for ANA positivity. Using the immunoblot technique, the sera of patients were assayed at dilutions of 1 : 40 and 1 : 100 for human autoantibodies of the IgG class to 15 lines of highly purified ENAs. RESULTS: In the IIF studies for ANA, positivity was identified for four different patterns in the 1 : 40 diluted preparations, for three different patients in the 1 : 100 diluted preparations and only one pattern was identified at the 1 : 320 dilution. In the ENA studies, positivity was identified for four different pattern in the 1 : 40 dilution, and only one pattern was identified at the 1 : 100 dilution. CONCLUSION: This study was not able to support the eventual existence of an autoimmune basis for IGM.

Granulomatous mastitis: is it an autoimmune disease? Diagnostic and therapeutic dilemmas.

PURPOSE: Granulomatous mastitis (GM) is a rare benign inflammatory breast disease. The clinical presentation of granulomatous mastitis usually mimics malignancy or infection. The aim of this study was to review the clinical and diagnostic features of GM and discuss the medical and surgical treatment of our series of eight GM patients. METHODS: Between 2008 and 2010, eight patients were diagnosed with GM and underwent surgery. Patients were evaluated clinically and radiologically. The diagnosis of GM was confirmed in all cases by core needle or excisional biopsies. Serological tests were performed for rheumatoid factor (RF), antinuclear antibody (ANA), and anti-double-stranded DNA (anti-dsDNA). RESULTS: The mean patient age was 37 years. Common presenting symptoms were a hard mass, pain, inflamed hyperemic skin, and sinus formation. Serological tests for RF were positive in 6 patients, and ANA and anti-dsDNA antibodies were detected in 2 patients. All patients underwent antibiotic therapy before surgery, and were treated with wide surgical excision with negative margins. Methylprednisolone (16 mg/day for 3 months) therapy was used in 3 patients (all RF and 2 ANA/anti-dsDNA positive) following a wide excisional biopsy after a postoperative recurrence mimicking skin lesions was seen. These patients responded well to steroid therapy. CONCLUSIONS: The diagnosis of GM should be made carefully to avoid a misdiagnosis. Steroid therapy should be considered based on the idea that this is an autoimmune disease.