Nonlactational mastitis in adults

INTRODUCTION — Mastitis refers to inflammation of the breast tissue that may or may not be accompanied by infection. Mastitis does not necessarily occur during lactation, is not always accompanied by microbial infection, and may not resolve with antibiotics. Forms of nonlactational mastitis include periductal mastitis and idiopathic granulomatous mastitis.

Issues related to nonlactational mastitis in adults will be reviewed here; issues related to lactational mastitis are discussed separately. (See "Lactational mastitis".)

PERIDUCTAL MASTITIS — Periductal mastitis is an inflammatory condition of the subareolar ducts; the cause is unknown. Periductal mastitis primarily affects young women but can occur in men as well.

The majority of patients with periductal mastitis are smokers. It has been postulated that smoking is associated with damage of the subareolar ducts, with tissue necrosis and subsequent infection [1,2]. The toxic substances in cigarette smoke may damage the ducts directly or there may be a localized hypoxic effect. In a study of 139 patients with the clinical or pathologic diagnosis of periductal mastitis, 89 percent were smokers (as compared with 39 percent of age-matched controls). The breast concentrates substances in cigarette smoke; cotinine, a nicotine derivative, has higher concentrations in subareolar ducts than in plasma [3-5].

Periductal mastitis is also associated with squamous metaplasia, which is likely a consequence of ongoing inflammation. It has been suggested that squamous metaplasia may lead to partial duct obstruction with subsequent dilatation and secondary inflammation and infection [2,6,7]. However, as normal ducts are blocked by keratin, it is the author's view that duct obstruction, duct dilatation, and squamous metaplasia are not precursors of periductal inflammation or relevant etiologic factors.

Clinical manifestations — Periductal mastitis is an inflammatory condition of the subareolar ducts that usually presents with periareolar inflammation [1,2,8,9]. Secondary infection of inflamed ducts can occur, leading to duct damage and subsequent rupture with abscess formation (picture 1). Such abscesses often drain spontaneously at the edge of the areola. Recurrent abscesses and a draining fistula (ie, communication between a major subareolar duct and the skin) (picture 2A-D) can occur [3,6,10-12]. (See 'Subareolar abscess and periareolar fistula' below.)

Diagnosis — The diagnosis of periductal mastitis is essentially clinical based on appearance. Ultrasound is typically performed to rule out abscess, if there is a mass or if signs of infection do not regress within a few days. Mammograms are not typically performed since they are less valuable and quite painful in the typically young patients in whom periductal mastitis occurs.

Differential diagnosis — Periductal mastitis must be distinguished from duct ectasia, which usually affects older women and is characterized by distension of subareolar ducts with fibrosis [13]. Duct ectasia is associated with creamy or cheesy nipple discharge and nipple inversion (picture 3) [14]. The dilated subareolar ducts may be apparent clinically and visible on imaging [15,16].

Originally, duct ectasia and periductal mastitis were considered part of the same clinical syndrome and the two terms were used interchangeably. However, duct ectasia is an age-related phenomenon and is not associated with significant periareolar inflammation or infection. Few women with duct ectasia have a history of prior periductal mastitis.

Periductal mastitis must also be differentiated from breast cancer. (See "Diagnostic evaluation of suspected breast cancer".)

Microbiology — Cultures are positive for pathogenic or potentially pathogenic organisms in 62 to 85 percent of cases [17-19]. In a series of 29 patients with periductal mastitis, pathogenic or potentially pathogenic organisms were observed more frequently in patients with nipple discharge and a periareolar mass than in patients with nipple discharge only (83 versus 27 percent, respectively) [17].

The most common organisms are staphylococci, enterococci, anaerobic streptococci, Bacteroides, and Proteus.

Management

Periductal mastitis — Periductal mastitis is usually a chronic problem. In the setting of purulent nipple discharge, Gram stain and culture should be obtained. Approximately half of the cases resolve with antibiotic therapy together with needle aspiration or incision and drainage of any associated abscess [7]. Patients with repeated episodes of periareolar infection warrant surgical treatment with excision of diseased ducts [20]. (See 'Subareolar abscess and periareolar fistula' below.)

Empiric antibiotic therapy for periductal mastitis consists of amoxicillin-clavulanate (875 mg orally every 12 hours). Reasonable alternative regimens include dicloxacillin (500 mg orally four times daily) or cephalexin (500 mg orally four times daily; with metronidazole [500 mg orally three times daily] if anaerobes are suspected) [18,21]. If risk for methicillin-resistant Staphylococcus aureus (MRSA) is high (table 1), trimethoprim-sulfamethoxazole (one double-strength tablet orally twice daily) or doxycycline (100 mg orally twice daily) is an appropriate regimen. In the setting of beta-lactam hypersensitivity, clindamycin (300 to 450 mg orally three times daily) is a reasonable alternative [17,18]. Therapy should be tailored to results of Gram stain and culture when available.

The optimal length of therapy is not certain; a 5- to 7-day course can be used if the response to therapy is rapid and complete; if necessary, the duration may be extended to 10 to 14 days.

Smoking cessation is helpful for reducing the risk of repeat infection [3].

Subareolar abscess and periareolar fistula — These conditions are usually complications of periductal mastitis. The management of subareolar abscess consists of antibiotic therapy (see 'Periductal mastitis' above) and abscess drainage. Needle aspiration or incision and drainage of an abscess is associated with recurrence of subareolar abscess in up to half of patients [3,7]. Infection recurs because these procedures do not remove the underlying periductal mastitis [1-4,22]. In one study, 33 of 67 cases of subareolar abscess were treated successfully with needle aspiration and antibiotics; the other 34 patients required definitive duct excision to healthy tissue [7]. Similar results have been reported in other clinical series [23].

The management of periareolar fistula is laying open the fistula or excision of the fistula tract, usually combined with a total duct excision [6-8,23,24]. Multiple ducts may be involved with multiple skin openings in some patients; all need to be resected for cure [25,26].

Total ductal excision can often be performed with local anesthesia and sedation or under general anesthesia as an outpatient procedure. The preferred surgical approach is via a circumareolar incision at the 6 o'clock position, unless a previous scar exists, in which case the scar can be reopened. Dissection is performed underneath the areola and down either side of the major ducts. Curved tissue forceps can be passed around the ducts to facilitate delivery of the ducts into the incision. The ducts are then divided from the undersurface of the nipple and a 2 cm portion of duct is removed (picture 2A-D).

The back of the nipple must be cleared of all ducts right up to the nipple skin, as infection may recur unless all residual diseased ducts are removed. Sutures rarely, if ever, need to be placed behind the nipple to maintain eversion of the nipple. If the nipple does not evert after resection of the diseased ducts, further dissection and division of fibrous tissue may be required. Subcutaneous tissue can be closed with fine interrupted absorbable sutures and the skin is closed with a running subcuticular absorbable suture. Patients should understand that this procedure results in reduced nipple sensitivity in almost 40 percent of cases [27].

Antibiotic treatment for periductal mastitis should be initiated at the time of surgery and be continued postoperatively until all signs of infection have resolved. (See 'Periductal mastitis' above.)

IDIOPATHIC GRANULOMATOUS MASTITIS — Idiopathic granulomatous mastitis (IGM), also known as idiopathic granulomatous lobular mastitis, is a rare benign inflammatory breast disease of unknown etiology [1,22,28-35]. It is usually unilateral, but in rare instances, it can be bilateral or develop later in the other breast.

Epidemiology and pathogenesis — IGM occurs most commonly in parous young women (within five years of pregnancy); it can also occur in nulliparous women and has been reported in men as well.

Women from Southeast Asia and the Middle East may have a higher incidence of IGM than those of European ancestry [36]. Among women in the United States, it has been associated with Hispanic ethnicity [34,37].

Hyperprolactinemia, whether drug induced or associated with a prolactin-producing pituitary adenoma, has been associated with IGM [38,39].

There is no increased risk of subsequent breast cancer in patients with IGM.

There may be an association between IGM and Corynebacterium kroppenstedtii infection especially, but not exclusively, with the histologic pattern termed cystic neutrophilic granulomatous mastitis [40-44]. Other Corynebacterium species have also been associated with IGM. In addition, mastitis due to C. kroppenstedtii has been associated with elevated prolactin levels [45]. Although antibiotics targeting Corynebacterium are often prescribed for IGM, there is no clear evidence that this approach alters the course of disease. Thus, corynebacteria may not be the causative factor in most patients with IGM.

Clinical manifestations — IGM may present as a solitary peripheral tender inflammatory breast mass; it can also present as multiple simultaneous peripheral masses (rarely central) with abscesses and/or overlying skin inflammation and ulceration (picture 4) [1,28-32]. Nipple retraction, sinus formation, peau d'orange-like changes, and axillary adenopathy may accompany these findings [46-49]. Women with IGM may develop repeated abscesses over weeks to months. These findings may be confused with breast abscess or malignancy [28].

Mammography may be suggestive of malignancy [50-55].

Diagnosis — Ultrasound is the initial investigation of choice. Ultrasound examination typically demonstrates a solid mass, often with one or more abscesses. The diagnosis of IGM is established via core needle biopsy of a solid mass visualized on ultrasound. The biopsy should be sent for Gram stain, bacterial culture, acid-fast bacilli stain and culture, fungal stain and culture, and histopathology. The microbiology laboratory should be alerted to clinical concern for Corynebacterium.

Biopsy findings typically demonstrate non-necrotizing granulomatous lesions centered on the breast lobule.

It is also reasonable to obtain a serum prolactin level, given a possible pathogenic link between hyperprolactinemia and IGM [45]. Testing to exclude tuberculosis, sarcoidosis, and fungal diseases in the appropriate clinical setting is appropriate. Routine testing for autoantibodies is not recommended [56].

Differential diagnosis — The differential diagnosis includes conditions such as tuberculosis, foreign body reaction, breast cancer, granulomatosis with polyangiitis, histoplasmosis, or rarely sarcoidosis, which may also induce a granulomatous mastitis. These etiologies should be identified on biopsy and/or microbiologic testing. (See "Diagnostic evaluation of suspected breast cancer".)

Management

Initial approach — Often, no specific management is necessary for IGM, especially in patients with small (<5 cm), unilateral lesions without sinus formation or abscess. It is frequently a self-limiting inflammatory condition that resolves slowly; complete resolution may take 5 to 20 months [57,58]. Surgical excision for IGM is often followed by slow wound healing and is not advocated. In a series of 120 women with IGM, most cases resolved spontaneously without surgical intervention or medications [58]. A meta-analysis of 10 retrospective studies from several countries (Turkey, Iran, Saudi Arabia, Japan, and the United States) demonstrated comparable recurrence rates between patients managed with or without surgery (odds ratio 1.25, 95% CI 0.51-3.03) [59]. In some cases, treatment is warranted for infection or symptom control.

IGM complicated by secondary infection and abscess, if treated with antibiotics and drainage, usually results in complication resolution [8,22,28,30]. Antibiotic selection should be dictated by culture and susceptibility testing. We generally start an antibiotic regimen used for periductal mastitis after specimens are collected for testing and then adjust based on microbiology results. Oral regimens are generally appropriate. (See 'Periductal mastitis' above.)

If only Corynebacterium is recovered, the optimal management approach is uncertain, in part because of the multiple species of Corynebacterium and the lack of predictable susceptibility patterns. In such cases, we suggest treatment with doxycycline (100 mg orally twice daily). If this fails to produce a response, linezolid (600 mg orally twice daily) can be used. In refractory or unusually severe cases, we favor speciating the Corynebacterium isolate and doing formal susceptibility testing, if available. Therapy can then be adjusted based on susceptibility testing [40,43,60]. The optimal length of therapy is also uncertain; a 5- to 7-day course can be used if the response to therapy is rapid and complete. If necessary, the duration may be extended to 10 to 14 days. While these antibiotics treat acute infection, there is little evidence that antibiotics shorten the time to full resolution of granulomatous lobular mastitis.

Localized pain may be managed with nonsteroidal anti-inflammatory drugs (NSAIDs). Routine use of steroids or methotrexate is not warranted. These therapies can reduce swelling but may not alter the natural history of the condition, especially in those with small, localized lesions. Discontinuation has been associated with rebound inflammation [28,52,61-65]. In patients with coincident hyperprolactinemia, treatment with bromocriptine, addressing the underlying cause of excess prolactin production by surgery, or drug substitution may be beneficial [39].

Persistent or refractory symptoms — Recurrence is common and is associated with lesion(s) size and number, skin ulceration, and the presence of fistulas [66,67]. The optimal management of patients with persistent symptoms and progression of IGM despite watchful waiting and antibiotics (if infection is present) and/or NSAIDs is uncertain; UpToDate contributors differ in their approach. Some find that treatment with steroids with or without methotrexate can be useful to reduce fever, pain, swelling, and possibly deformity. However, others do not use these agents, as there are no controlled studies demonstrating that they alter the natural history of the condition. Expectant management with observation has resulted in resolution of IGM in several small series [30,58,68].

The contributors who do use steroids in this setting base the approach on the size and severity of the lesion. In patients not responding to conservative management with painful, small (<5 cm) unilateral lesions with small amounts of drainage or ulceration, treatment with prednisone (0.5 mg/kg/day) may be initiated. In patients with multiple lesions, lesions ≥5 cm in diameter, bilateral lesions, or disease with significant cutaneous ulceration, drainage, or fistulas, treatment with prednisone (0.5 to 1 mg/kg/day) may be initiated, with or without methotrexate (10 to 15 mg orally per week, along with daily folic acid supplementation) [33,37,61,63,65,69,70]. In one observational study including 19 patients with IGM, most of whom were refractory to antibiotics, steroids, and surgical intervention, use of methotrexate was associated with disease remission in 75 percent of cases [69]. There are also reports indicating that intralesional triamcinolone and topical steroids are effective in treating this condition [71,72]. These approaches have the advantage of limiting the adverse effects of systemic steroid use.

Patients treated with steroids should begin tapering when erythema and pain have resolved (usually after about four weeks). Prednisone is tapered gradually over 8 to 12 weeks. If flares occur during tapering in patients on steroids alone, methotrexate (10 to 15 mg per week) may be added. If flares occur during tapering in patients on steroids and methotrexate, small increases in the methotrexate dose (by 2.5 to 5 mg every few weeks) is appropriate. Once clinical remission has been achieved, the methotrexate dose should be reduced monthly; many patients are able to discontinue therapy within 12 months [73]. Monitoring the lesions with weekly photographs may be helpful. Repeat ultrasonography may be useful if there is suspicion for new lesions or abscess reaccumulation.

TUBERCULOUS MASTITIS — Tuberculous mastitis is an uncommon entity, even in countries that have a high incidence of pulmonary tuberculosis. It most commonly affects women of reproductive age, including those who are lactating; cases in men are exceedingly rare [74-78].

Clinical manifestations — The most common clinical finding is a solitary breast lump [74-78]. The lump is typically painful, ill-defined, and irregular; it is occasionally firm. Involvement of the nipple and areola is very uncommon.

Although the disease frequently involves the skin, the breast usually remains mobile on the chest wall unless there is also tuberculosis involving the underlying ribs. Both breasts are affected in up to 3 percent of patients. Common associated features are multiple sinuses, fistulous tracts, and enlarged axillary nodes, which can be matted. Tuberculous mastitis can also present with an ulcer. The overlying skin may be thickened with ulceration or sinus tracts with purulent discharge either from the ulcer or from the nipple. In later stages there may also be multiple tender areas of irregular masses, multiple sinuses and areas of pus. The sclerosing stage can lead to breast shrinkage.

Most patients have had symptoms for a few months prior to presentation, but duration of symptoms can last up to several years [74-78].

On ultrasound, tuberculous mastitis can appear as a solitary mass or multiple masses that are well-circumscribed and grow slowly. The mass may mimic a fibroadenoma in the early stages of disease and a carcinoma in the later stages. Ultrasound may also demonstrate communications between breast lesions and fistulous tracts as well as blind ended sinuses [74-79].

Mammographic findings are generally similar to those with breast malignancies [74-79].

There are no routine laboratory findings specific to tuberculous mastitis.

Diagnosis — Although it is rare, the possibility of tuberculous mastitis should be suspected in a patients with epidemiologic risk for tuberculosis who has a breast lesion that does not resolve with antibiotics, particularly if there are sinuses or fistulous tracts connecting multiple lesions. In some cases, the diagnosis is not suspected until biopsy of a lesion for the purpose of ruling out malignancy demonstrates necrotizing granulomas. The diagnosis is confirmed by growth of tuberculosis on culture of breast biopsy specimen.

Core needle biopsy of both the primary breast lesion as well as any abnormal axillary lymph nodes is essential for diagnosis. Breast masses can be initially assessed by ultrasound, which is valuable at assessing regional nodes and directing biopsies both in the breast and axilla.

When evaluating for tuberculous mastitis, one or two core tissue samples from the breast and/or axilla should be sent for acid-fast bacilli (AFB) smear and culture. Culture of pus or drainage is insufficient to detect tuberculosis, as mycobacteria in these specimens are difficult to grow.

Histologically, a finding of a granulomatous lesion with Langhans’ giant cells, is indicative of tuberculosis but cannot confirm the diagnosis. It is often difficult to demonstrate any AFB histologically.

Once the diagnosis of tuberculous mastitis is established, chest imaging should be performed to evaluate for potential pulmonary involvement. (See "Diagnosis of pulmonary tuberculosis in adults".)

Differential diagnosis — Tuberculous mastitis can been mistaken for other inflammatory conditions, including bacterial breast abscess and breast cancer. Bacterial breast abscess can be diagnosed by aspiration under ultrasound guidance followed by AFB culture and stain. Breast cancer can be distinguished by core biopsy under ultrasound guidance by pathologic diagnosis of the sample. (See "Diagnostic evaluation of suspected breast cancer".)

Management — Once culture identifies mycobacteria, the treatment approach is similar to pulmonary tuberculosis. An initial four drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) for two months is typically given, followed by an additional four months with isoniazid and rifampin, if the organism is susceptible. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

Even after successful treatment of the infection, the breast can be significantly scarred and may warrant revision surgery [74-79].

SUMMARY AND RECOMMENDATIONS

●Definitions – Mastitis refers to inflammation of the breast tissue that may or may not be accompanied by infection. Mastitis does not necessarily occur during lactation, is not always accompanied by microbial infection, and may not resolve with antibiotics. Forms of nonlactational mastitis include periductal mastitis and idiopathic granulomatous mastitis. (See 'Introduction' above.)

●Periductal mastitis – Periductal mastitis is an inflammatory condition of the subareolar ducts that usually presents with periareolar inflammation. (See 'Periductal mastitis' above.)

•Occurrence of infection – Secondary infection of inflamed ducts can occur, leading to duct damage and subsequent rupture with abscess formation. A draining fistula (ie, communication between a major subareolar duct and the skin) can also develop. (See 'Clinical manifestations' above.)

•Microbiology and diagnosis of infection – In the setting of purulent nipple discharge, Gram stain and culture should be obtained. Cultures are positive for pathogenic or potentially pathogenic organisms in 62 to 85 percent of cases. The most common organisms are staphylococci, enterococci, anaerobic streptococci, Bacteroides, and Proteus. (See 'Microbiology' above.)

•Clinical course and management of infection – Periductal mastitis is usually a chronic problem. Approximately half of cases resolve with antibiotic therapy together with needle aspiration or incision and drainage. Patients with repeated episodes of periareolar infection warrant surgical treatment with ductal excision. (See 'Management' above.)

●Idiopathic granulomatous mastitis (IGM) – This syndrome, also known as idiopathic granulomatous lobular mastitis, is a rare benign inflammatory breast disease of unknown etiology. IGM is most commonly seen in parous young women, often within a few years of pregnancy, although it can occur in nulliparous women. There is no increased risk of subsequent breast cancer in patients with IGM. (See 'Idiopathic granulomatous mastitis' above.)

•Diagnosis of IGM – The diagnosis of IGM is established via core needle biopsy of a solid mass.

•Management of IGM – IGM associated with a localized infection usually resolves with antibiotics and drainage. Surgical excision for IGM is often followed by slow wound healing and is not advocated. The optimal management of persistent symptoms is uncertain and approaches differ. (See 'Diagnosis' above and 'Management' above.)

●Tuberculous mastitis – Tuberculosis of the breast is an uncommon entity that affects women of reproductive age including those who are lactating. Core needle biopsy is essential for diagnosis. Histologically, a finding of a granulomatous lesion with Langhans’ giant cells is indicative of tuberculosis. Treatment is similar to that for pulmonary tuberculosis. (See 'Tuberculous mastitis' above and "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

●Differential diagnosis and role of biopsy – The differential diagnosis for nonlactational mastitis includes breast cancer, which underscores the importance of biopsy in these cases, especially if there is uncertainty or lack of response to therapy. (See "Diagnostic evaluation of suspected breast cancer".)