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Systemic vasculitis involving the breast: a case report and literature review

  • Jiaqi Ren
  • Jianying Liu
  • Jing Su
  • Jingfeng Zhang
  • Jinxia ZhaoEmail author
Open Access
Case Based Review
  • 128 Downloads

Abstract

Systemic vasculitis involving the breast is a rare clinical condition and may mimic breast cancer or mastitis clinically or radiographically. Here, we report a case of polyarteritis nodosa (PAN) with breast involvement and perform a literature review of published cases of systemic vasculitis affecting the breast to better understand this disorder. We report a case of PAN affecting the right breast in a young woman. A retrospective review was performed by searching Medline, Embase, Web of Science, the Cochrane Library, and Scopus for cases of systemic vasculitis involving the breast written in English up to June 1st, 2018. A 27-year-old woman presented with a painful mass in the right breast was diagnosed as PAN by the biopsy. She was treated with prednisone and methotrexate for 6 months, at which time her condition had stabilized and inflammatory markers had normalized. A total of 66 cases were identified, with granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and PAN as the main types. The typical manifestation was mass (79.2%, 53/67) in the breast, and all diagnoses were made by the pathology of the breast biopsy. Glucocorticoid and immunosuppressant were the main therapies, and 74.6% (50/67) patients achieved remission during follow-up. Our case and a literature review of 66 cases of systemic vasculitis involving the breast reveal the importance of tissue biopsy to obtain a definitive diagnosis, because the vasculitis subtype strongly influences prognosis.

Keywords

Systemic vasculitis Breast 

Introduction

Systemic vasculitis is a group of heterogeneous diseases which mainly manifests as inflammation of the blood vessels. Nearly all organs can be affected, but the skin, kidney, and upper and lower respiratory tract are most commonly involved [1]. However, the breast has rarely been reported as the involved site of systemic vasculitis [2, 3]. Here, we report such a case and perform a review on the published cases of systemic vasculitis involving the breast. The results will help to further delineate the clinical presentation, course, and treatment of this disease.

Case report

A 27-year-old woman came to our hospital with a 40-day history of swollen and painful right breast, with a palpable mass in the outer portion of the breast. She also reported polyarthralgia of 10-day duration. On presentation, she had a low-grade fever but no other discomforts, such as fatigue, cough, rash, myalgia, or oral ulcers. As acute mastitis was considered as a possible diagnosis, she was treated with intravenous antibiotics for 5 days. However, the mass became purulent and fluctuant. Breast ultrasound showed multiple hypoechoic areas near the outer portion of the right breast and the nipple. Incision and drainage of the right breast were performed, and cefazolin and ornidazole were prescribed for 10 days. Although the symptom of her breast did not become any better, the body temperature returned to normal. Ten days later, multiple joints became persistent painful, including bilateral knee, ankle, wrist, hip, and metacarpophalangeal joints. Her left ankle joint became swollen, and erythema appeared on the left ankle joint and both sides of the anterior tibiae near the knee joints. The ankle lesion was initially about 3 cm in diameter but expanded to 8 cm and was accompanied by an increase in skin temperature. The patient’s body temperature rose to 38.5 °C, and she experienced chills. She was prescribed ibuprofen and metamizole sodium without effect, and she experienced a 5-kg loss of body weight in 1 month.

At first admission to our hospital, the patient’s temperature was at 38.7 °C, but other vital signs were normal. Physical examination revealed an unhealed wound in the right breast, with rupture and little blood and fluid oozing on the surface. A small amount of necrotic tissue could be seen on the surface, as shown in Fig. 1a. Erythema nodosum was present on the left ankle joint and both knee joints, which were tender upon gentle palpation, without itching and peeling. There was also tenderness on both sides of the gastrocnemius muscle. Laboratory findings disclosed the following: white blood cell count: 10.2 × 109/L (normal: 3.5–9.5 × 109/L); neutrophil proportion: 84.3% (normal: 40–75%); hemoglobin: 108 g/L (normal: 130–175 g/L); calcitonin: 0.131 ng/mL (normal: < 0.1 ng/mL); erythrocyte sedimentation rate (ESR): 52 mm/h (normal: 0–20 mm/h); C-reactive protein (CRP): 148 mg/L (normal: ≤ 8 mg/L). Abnormal liver function was evident: alanine aminotransferase (ALT): 124 U/L (normal: 9–50 U/L), aspartate aminotransferase (AST): 54 U/L (normal: 15–40 U/L); γ-glutamyl transferase (γ-GT): 676 U/L (normal: 9–50 U/L); alkaline phosphatase (ALP): 381 U/L (normal: 45–125 U/L). Serum immunoglobulin E level was elevated at 700 IU/mL (normal: < 100 IU/mL), as was complement factor C4 (0.421 g/L, normal: 0.12–0.40 g/L). Other routine biochemical tests, including renal function tests, were normal. Pituitary prolactin was normal, and an autoantibody screen was negative (rheumatoid factor, and antinuclear and anti-neutrophil cytoplasmic antibodies). Chest computed tomography reveled a soft-tissue mass on the right breast and swollen axillary lymph nodes on the same side. Ultrasound showed obvious swelling of subcutaneous soft tissue around the left ankle joint and the dorsum of the foot, and effusion of the talofibular joint. Ultrasound of her left knee joint also showed swelling of the subcutaneous soft tissue, but no joint effusion or synovitis. No arterial or venous thromboses of the bilateral legs were noticed on the ultrasound.

Fig. 1

The clinical manifestation of the patient’s right breast. a Before treatment: a painful mass on the outer portion of right breast, with rupture and blood and fluid oozing on the surface. b After treatment: the wound had got well healed

In the current reported case, the patient complained of polyarthralgia, which prompted us to consider arthritic disease, such as reactive arthritis, rheumatoid arthritis, or some other diseases at first, and the symptoms on her right breast might be caused by infection, tuberculosis, or malignancy. However, the negative autoantibody screen, elevated ESR and CRP level, and the failure of the breast to heal after full course of antibiotics were puzzling.

To make a diagnosis, biopsy of the lesion on the right breast was performed. Histological analysis indicated inflammatory necrosis and multiple arterioles [positive for α-smooth muscle actin (SMA), CD31, elastic fiber staining] were presented as proliferative obliterate endarteritis in granulation tissue, which was highly suggestive of nodular arteritis or another type of vasculitis (Figs. 2, 3). Biopsy of the nodular erythema on the knee showed infiltration of the vascular wall by inflammatory cells, mainly lymphoid mononuclear cells and a few neutrophils. The inflammation involved small vessels and the periphery of the fat lobule, which is in agreement with changes observed in skin vasculitis, especially PAN. Therefore, the diagnosis of PAN was considered. Full-dose prednisone (1 mg/kg/day) and methotrexate (15 mg/week) were prescribed, and the breast lesion healed after 2 weeks of treatment. Six months later, her condition kept stable (Fig. 1b) and inflammatory markers remained normal. Timeline of clinical features and interventions were summarzied in Fig. 4).

Fig. 2

Photomicrographs of the patient’s right breast biopsied specimen. Occlusion of the vessel, destruction of the vascular wall infiltrated with inflammatory cells, mainly lymphocytes, and a small amount of neutrophils (hematoxylin and eosin stains; original magnification ×100)

Fig. 3

Photomicrographs of the patient’s right breast biopsied specimen. This confirmed that the involved vessels were arteries (elastic fibers staining; original magnification ×100)

Fig. 4

Timeline of clinical features and interventions

Search strategy

Data sources and searches

We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for cases of systemic vasculitis involving the breast published in English up to June 1st, 2018. The search terms were arteritis, vasculitis, and breast. We reviewed the abstracts of relevant studies and retrieved appropriate articles. We also scrutinized the reference lists of the included studies to identify additional references.

Study selection

Two authors independently scanned the titles and abstracts for the following inclusion criteria: (1) cases of systemic vasculitis involving the breast, (2) published in English language, and (3) published in a peer-reviewed journal. Reviews and other study types lacking clinical data from individual patients were excluded. There was no disagreement between the two reviewers at any point in the selection process.

Data extraction and study quality assessment

Two investigators extracted the following data independently using a standard form: author, publication year, clinical history, laboratory values, histopathologic features, treatment, and outcomes [4].

Results

In addition to our case, 66 cases were identified by the literature review (Table 1). Detailed patient characteristics are shown in Table 1. The main types of vasculitis affecting the breast were granulomatosis with polyangiitis (GPA, n = 23), giant cell arteritis (GCA, n = 17), and PAN (n = 17). Three cases of eosinophilic granulomatosis with polyangiitis (EGPA) [5, 6, 7], three of Behcet’s disease [8, 9, 10] and two of microscopic polyangiitis (MPA) [11, 12], and two of unclassified vasculitis made up the remainder of the 67 cases.

Table 1

The summary of the characteristics of the patients

 

PAN

GPA

GCA

MPA

EGPA

Behcet’s disease

Others

Total

Case number % (no./total no.)

25.4 (17/67)

34.3 (23/67)

25.4 (17/67)

3 (2/67)

4.5 (3/67)

4.5 (3/67)

3 (2/67)

100 (65/67)

Mean age ± SD (years)

52.4 ± 18.2

49.8 ± 12.4

63.6 ± 7.4

45.5 ± 20.5

64.0 ± 14.2

36.6 ± 12.5

61.0 ± 7.1

54.2 ± 14.7

Gender % (no./total no.)

 Male

0 (0/17)

4.3 (1/23)

0 (0/17)

0 (0/2)

33.3 (1/3)

0 (0/3)

0 (0/2)

3 (2/67)

 Female

100 (17/17)

95.7 (22/23)

100 (17/17)

100 (2/2)

66.7 (2/3)

100 (3/3)

100 (2/2)

97 (65/67)

Duration % (no./total no.)

 ≤ 1 month

35.3 (6/17)

34.8 (8/23)

64.7 (11/17)

0 (0/2)

0 (0/3)

33.3 (1/3)

0 (0/2)

38.8 (26/67)

 > 1 month

35.3 (6/17)

30.4 (7/23)

11.8 (2/17)

100 (2/2)

100 (3/3)

33.3 (1/3)

100 (2/2)

34.3 (23/67)

 NA

29.4 (5/17)

34.8 (8/23)

23.5 (4/17)

0 (0/2)

0 (0/3)

33.3 (1/3)

0 (0/2)

26.9 (18/67)

Formation % (no./total no.)

 Mass

88.2 (15/17)

91.3 (21/23)

88.2 (15/17)

0 (0/2)

0 (0/3)

66.7 (2/3)

0 (0/2)

79.1 (53/67)

 Ulcer

5.9 (1/17)

0 (0/23)

0 (0/17)

0 (0/2)

0 (0/3)

33.3 (1/3)

0 (0/2)

3 (2/67)

 Others

5.9 (1/17)

8.7 (2/23)

11.8 (2/17)

100 (2/2)

100 (3/3)

0 (0/3)

100 (2/2)

17.9 (12/67)

Bilateral % (no./total no.)

 Yes

35.3 (6/17)

17.4 (4/23)

41.2 (7/17)

50 (1/2)

67.7 (2/3)

33.3 (1/3)

50 (1/2)

32.8 (22/67)

 No

64.7 (11/17)

82.6 (19/23)

58.8 (10/17)

50 (1/2)

33.3 (1/3)

67.7 (2/3)

50 (1/2)

32.8 (22/68)

Extramammary % (no./total no.)

 Yes

64.7 (11/17)

87 (20//23)

64.7 (11/17)

100 (2/2)

100 (3/3)

100 (3/3)

100 (2/2)

77.6 (52/67)

 No

35.3 (6/17)

13.0 (3/23)

35.3 (6/17)

0 (0/2)

0 (0/3)

0 (0/3)

0 (0/2)

22.4 (15/67)

ESR % (no./total no.)

 Normal

11.8 (2/17)

8.7 (2/23)

0 (0/17)

0 (0/2)

0 (0/3)

0 (0/3)

100 (2/2)

9 (6/67)

 High

70.6 (12/17)

43.5 (10/23)

82.4 (14/17)

100 (2/2)

33.3 (1/3)

33.3 (1/3)

0 (0/2)

59.7 (40/67)

 NA

17.6 (3/17)

47.8 (11/23)

17.6 (3/17)

0 (0/2)

67.7 (2/3)

66.7 (2/3)

0 (0/2)

31.1 (21/67)

CRP % (no./total no.)

 Normal

17.6 (3/17)

4.3 (1/23)

0 (0/17)

0 (0/2)

0 (0/3)

0 (0/3)

50 (1/2)

7.5 (5/67)

 High

47.1 (8/17)

26.1 (6/23)

23.5 (4/17)

100 (2/2)

33.3 (1/3)

0 (0/3)

50 (1/2)

32.8 (22/67)

 NA

35.3 (6/17)

69.6 (16/23)

76.5 (13/17)

0 (0/2)

67.7 (2/3)

100 (3/3)

0 (0/2)

59.7 (40/67)

ANCA % (no./total no.)

 Negative

47.1 (8/17)

8.7 (2/23)

11.8 (2/17)

0 (0/2)

33.3 (1/3)

0 (0/3)

0 (0/2)

19.4 (13/67)

 Positive

23.5 (4/17)

43.5 (10/23)

5.9 (1/17)

100 (2/2)

33.3 (1/3)

0 (0/3)

50 (1/2)

28.4 (18/67)

 NA

29.4 (5/17)

47.8 (11/23)

82.4 (14/17)

0 (0/2)

33.3 (1/3)

100 (3/3)

50 (1/2)

52.2 (35/67)

Glucocorticoid % (no./total no.)

 Yes

58.5 (10/17)

73.9 (17/23)

58.8 (10/17)

100 (2/2)

100 (3/3)

33.3 (1/3)

50 (1/2)

65.7 (44/67)

 No

29.4 (5/17)

21.7 (5/23)

35.3 (6/17)

0 (0/2)

0 (0/3)

66.7 (2/3)

50 (1/2)

28.4 (19/67)

 NA

11.8 (2/17)

4.3 (1/23)

5.9 (1/17)

0 (0/2)

0 (0/3)

0 (0/3)

0 (0/2)

4 (4/67)

Immunosuppressant % (no./total no.)

 Yes

23.5 (4/17)

69.6 (16/23)

0 (0/17)

100 (2/2)

33.3 (1/3)

0 (0/3)

100 (2/2)

37.3 (25/67)

 No

64.7 (11/17)

26.1 (6/23)

94.1 (16/17)

0 (0/2)

0 (0/3)

0 (0/3)

0 (0/2)

49.3 (33/67)

 NA

11.8 (2/17)

4.3 (1/23)

5.9 (1/17)

0 (0/2)

67.7 (2/3)

100 (3/3)

0 (0/2)

13.4 (9/67)

Outcomes % (no./total no.)

 Remission

76.5 (13/17)

82.6 (19/23)

82.4 (14/17)

0 (0/2)

33.3 (1/3)

67.7 (2/3)

50 (1/2)

74.6 (50/67)

 No remission

5.9 (1/17)

0 (0/23)

11.8 (2/17)

50 (1/2)

0 (0/3)

33.3 (1/3)

50 (1/2)

9 (6/67)

 Died

6.3 (1/17)

13 (3/23)

0 (0/17)

50 (1/2)

33.3 (1/3)

0 (0/3)

0 (0/2)

9 (6/67)

 NA

11.8 (2/17)

4.3 (1/23)

5.9 (1/17)

0 (0/2)

33.3 (1/3)

0 (0/3)

0 (0/2)

7.5 (5/67)

The patients with breast-involved vasculitis were 54.2 ± 14.7 years of age (mean ± SD) with a range of 21 [13] to 78 [14] years. However, the mean ages of patients with different types of vasculitis varied. Among the 67 cases, the disease duration ranged from a few weeks to several months. Breast involvement was the first symptom in some patients and appeared after diagnosis or treatment in others. The typical formation was a mass. Primary ulceration of the breast occurred in only two patients [9, 15], but could have been secondary to the breast mass. Bilateral involvement of the breast was about twice as common as unilateral involvement. Breast involvement alone was observed in only 22.4% (15/67) patients, mainly PAN and GCA patients, whereas the majority (77.6%) presented with extramammary manifestations such as myalgia, arthralgia, headache, rash, cough, and hematuria.

As for the laboratory test, anemia was found in some cases. Inflammatory parameters of ESR and CRP were commonly elevated in all kinds of systemic vasculitis. Diagnosis of all cases was made after breast biopsy and pathological examination, because mammography and ultrasound of the breast were not specific for the diagnosis. As shown in Table 2, 25/67 patients underwent mammography, with the results ranging from normal to increased dense mammary parenchyma, heterogeneous breast tissue, vascular calcification, skin or trabecular thickening, and nodular masses. Ultrasound was performed in 18 patients, which revealed 11.1% (2/18) with skin thickening, 55.56% (10/18) with lesions with or without necrosis or calcifications, 22.2% (4/18) with hypoechoic mammary parenchyma or infiltration of the breast, and 11.1% (2/18) with penetration of the blood vessels. Notably, 35.0% (7/20) and 30.0% (6/20) patients with mass detected on breast examination could be detected on mammography and ultrasound, respectively.

Table 2

The mammography and ultrasound features of the patients

Authors

Year

Diagnosis

Formation

Mammography

Breast ultrasound

Lee [20]

2017

PAN

Mass

Heterogeneously dense, mild skin thickening, increased parenchymal densities, trabecular thickening in both breasts

Skin thickening, increased echogenicity in the subcutaneous fat layer of both breasts, tubular and reticular anechoic fluids within the fat layer, no definite mass, but hypoechoic circumferential wall thickenings of the artery with perivascular fat infiltration along the vessel

Griffiths [21]

2017

PAN

Mass

No architectural distortions and calcifications

 

Shimamura [22]

2015

PAN

Mass

No architectural distortions and calcifications

No architectural distortions and calcifications

Khalil [9]

2009

PAN

Mass

No fibro-glandular parenchyma

A 2.0 cm complex cyst with internal echoes of low signal intensity and a rather irregular thickened capsule

  

PAN

Tenderness

Vascular calcifications throughout both breasts, no focal masses

Inflamed fibro-glandular tissue in the retroareolar region

Hong [23]

2007

PAN

Mass

A 1.8 cm, heterogeneous and irregular shaped mass-like lesion

Multifocal microcalcifications

Orbo [14]

1989

PAN

Mass

A dense area in the right mammary gland above the nipple, calcification of arteries in both breasts

 

Lluch [13]

2018

GPA

Mass

Several solid nodules with ill-defined margins in the right breast

Various hyperechoic solid lesions, some of them with anechoic areas of necrosis

Ryba [24]

2017

GPA

Thickening

 

Knobby changes in the right breast

Mengoli [25]

2017

GPA

Mass

 

A retro areolar, hypoechoic, irregularly shaped and partially necrotic lesion (3.7 cm across), no lymphadenopathy

Georgescu [26]

2015

GPA

Mass

 

A poorly defined mass in the left breast with multiple pleomorphic calcifications inside the mass and in its proximity

Neralic-Meniga [18]

2006

GPA

Mass

Multiple, delineated masses within the heterogeneous parenchyma, without associated micro calcifications

Multiple solid hypoechoic lesions with a homogeneous internal echo pattern and smooth margins, anechoic areas of necrosis in some of the lesions

Erysami [27]

2006

GPA

Mass

A 1.9 cm × 1.7 cm lesion

A 1.9 cm × 1.7 cm lesion

Stappaerts [19]

1999

GPA

Mass

 

Compatible with the presence of a malignant tumor

Gobel [28]

1995

GPA

Mass

A large opacification with a indistinct border in right breast

 

Deininger [29]

1985

GPA

Mass

A poorly outlined mass with diameter of 2.5–3.0 cm with an heterogeneous structure and radian sours

 
  

GPA

Induration

Heterogeneous structure and poorly bounded mass with cordlike indurations to the nipple and thickening of the skin

 

Hinze [30]

2011

GCA

Mass

Heterogeneous density breast tissue

 

Kadotani [15]

2010

GCA

Mass

Bilateral vascular calcification with dense mammary parenchyma but no evidence of malignancy

Slightly hypoechoic mammary parenchyma, no mass lesions in the breasts

Kafantari [31]

2008

GCA

Mass

A mass measuring 2 cm × 1.5 cm, causing a significant disruption in the architecture of the surrounding breast tissue

 

Marie [32]

2008

GCA

Mass

Normal

 

Anim [33]

2004

GCA

Tenderness

No definite masses or changes to suggest malignancy, but infiltration in the upper outer quadrants of both breasts

Infiltration of both breasts, no definite masses or changes to suggest malignancy

Kim [30]

1990

GCA

Mass

No mass lesions, but several enlarged heterogeneous echogenicity without any definite fluid collection

 

Lee [34]

2017

EGPA

None

A 2.3 × 1.1 × 0.4 cm area of altered echotexture in the left breast

A 2.3 × 1.1 × 0.4 cm area of altered echotexture in the left breast

Visentin [2]

2012

EGPA

Edema

Bilateral gynecomastia with skin thickening and mammary fat reticulation, lymphatic stasis involving the left breast

A bilateral gynecomastia with signs of lymphatic stasis involving the left breast

Devinck [7]

2011

MPA

Redness

A retro areolar lesion of 2.5 cm in diameter with penetration of the blood vessels

A retro areolar lesion of 2.5 cm in diameter with penetration of the blood vessels

Villalba-Nuno [3]

2002

EGPA

Redness

Bilateral diffuse increase in parenchymal density with skin thickening

Bilateral diffuse increase in parenchymal density with skin thickening

Soleto [4]

2002

Behcet’s disease

Mass

Increased focal density in the retroareolar mammary parenchyma

A hypoechoic nodule with poorly defined margins located at radial

Zardawi [35]

2004

Others

Redness

A slight increase in the density of the right breast tissue

 

The main therapies for systemic vasculitis involving the breast were glucocorticoid and immunosuppressant. Of the 67 patients, 44 (65.7%) received oral or intravenous glucocorticoid. Of these, 16 patients were treated with glucocorticoids alone and remitted, and 28 patients were given combined therapy with glucocorticoid and immunosuppressant, mainly cyclophosphamide and azathioprine. Besides, some patients became well after rituximab [2], mastectomy [14, 16], loxoprofen sodium [17], or even no treatment [18]. Noticeably, the intensity of treatment differed for breast vasculitis. For GCA patients, no patients received immunosuppressant, but achieved high proportion of remission (10/17, 82.7%) and no one died due to this disease. The proportion of using glucocorticoid was higher in GPA patients (17/23, 73.9%) than PAN patients (10/17, 58.5%), as well as use of the immunosuppressant (16/23, 69.6% vs 4/17, 23.5%), and remission rate (19/23, 82.6% vs 13/17, 76.5%). In general, the prognosis for patients with systemic vasculitis involving the breast was relatively good, with 74.6% (50/67) achieving remission during follow-up, but there were still five patients [5, 12, 13, 19, 20, 21] dead due to the involvement and failure of vital organs. Although only two patients were diagnosed with MPA, neither achieved remission.

Discussion

The breast is a rare organ that can be affected by systemic vasculitis. The first case of systemic vasculitis with breast involvement was GCA, reported in 1950 by Waugh [22]. By now, GPA, PAN, EGPA, MPA, and Behcet’s disease of the breast have been reported.

Our literature review identified 66 additional cases of vasculitis involving the breast. In some cases, the precipitating factor for breast involvement could be found; for example, mammoplasty [23], silicone breast implants [12, 24], radiotherapy of the breast [25], and invasive ductal carcinoma of the breast [26].

Symptoms of breast involvement can occur at the time of diagnosis or later on. There are two basic manifestations of the breast: masses and ulcerations. Compared to the limited manifestation of the breast, the external manifestations of mammary are more common. Systemic symptoms, including fever, fatigue, weight loss, arthralgia, and rash, can be signs for systemic vasculitis, but are not specific for the disease subtype. Several characteristic features are helpful for classifying vasculitis. For example, polymyalgia rheumatica (PMR)-like symptoms and involvement of the carotid arteries and their branches, especially temporal arteries, are commonly associated with GCA [27]. A history of asthma, allergic rhinitis, and paranasal sinusitis can be helpful in diagnosing EGPA.

Radiological manifestations of the breast are various, as mentioned above, but none is specific for vasculitis, let alone the category. Imaging findings included calcifications and vessel penetration [11, 13, 16, 17, 28], but were detected at low rates (5/47) by mammography and breast ultrasound. Nodular lesions were easily detected; however, they can be mistaken for malignant lesions, leading to mastectomy or wide excision that was unnecessary for the treatment of breast vasculitis. Some images revealed homogeneous or increased dense mammary parenchyma [16, 17, 27, 28, 29, 30], suggesting the presence of both multiple small nodules and diffuse edema. Taken together, these findings suggest that mammography and breast ultrasound are not reliable for the diagnosis of breast vasculitis.

The diagnosis made by the biopsy and pathology of the breast should be the gold diagnostic criteria, which have been illustrated very clearly in many papers [3, 5, 28, 31]. Histologically, it is easy to distinguish vasculitis from malignancy, but not from non-puerperal mastitis, which encompasses all causes of inflammatory changes in the female breast and mammilla not related to lactation. The etiology of non-puerperal mastitis is still unknown, with mammary duct ectasia (MDE), periductal mastitis (PDM), and granulomatous lobular mastitis (GLM) being the most frequent subtype classifications. No vessels should be involved, which is the main difference from vasculitis. Thus, vessel-specific stains, like SMA, CD31, and elastic fibers stains, can be helpful for the diagnosis of vasculitis.

Other differential diagnoses include malignancy of the breast [32, 33], sarcoidosis, fungal infections, tuberculosis, and Mondor’s disease [3, 31, 33], all of which have been clearly described in previous articles. In our case, unclassified systemic vasculitis cannot be completely excluded based on the histopathology. However, as the main vessels involved were muscular arterioles, and the clinical manifestation of the patient including fever, weight loss, polyarthralgia, erythema, and the tenderness on both sides of the gastrocnemius muscle, all point to PAN as the most likely diagnosis.

Once the diagnosis was made, the treatment of this disease was straightforward, mainly, consisting mainly of glucocorticoid and immunosuppressant therapy. In general, prognosis was good and most patients achieved remission within a few months of treatment. However, the treatment regimen and outcomes differed for each disease subtype. Most GCA patients entered remission by the single drug of glucocorticoid, but, for GPA patients and PAN patients, most of whom need immunosuppressant on the basic treatment of glucocorticoid could get good prognosis, as well. Unlike them, the prognosis of MPA patients was the worst. Collectively, the analysis of our patient and the literature indicate that distinction between localized and systemic involvement is critical for treatment, because systemic involvement, particularly the kidneys, heart, and liver, carries a poor prognosis.

Conclusion

In total, we reviewed the clinical features and outcome of 67 cases of systemic vasculitis involving the breast, which included GPA, GCA, PAN, MPA, EGPA, and Behcet’s disease. Tissue biopsy is essential for making diagnosis, and the prognosis of diseases is relatively good, but upon to the types.

Notes

Acknowledgements

We thank Anne M. O’Rourke, PhD, from Liwen Bianji, Edanz Group China (http://www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Author contributions

JR has finished the search of the literatures, analysis of the data, and the writing of the whole manuscript. JL and JS are pathologists who made the diagnosis of the biopsy of the patient’ breast and skin tissues. JZ is the physician who treated this patient and made the search of the literatures. JZ is the corresponding author of the manuscript who guided the writing and made the corrections of the whole paper. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Funding

None.

Compliance with ethical standards

Conflict of interest

Jiaqi Ren, Jianying Liu, Jing Su, Jingfeng Zhang, and Jinxia Zhao declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All authors fulfilled the ICMJE authorship criteria.

Informed consent

Written informed consent was obtained from the patient prior to submission of this article for consideration as a case-based review.

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© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Department of Rheumatology and ImmunologyPeking University Third HospitalBeijingChina
  2. 2.Department of Pathology, School of Basic Medical SciencesPeking UniversityBeijingChina

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