Figure 1. Classic representation of Raynaud phenomenon of the nipple. Note the obvious blanching (or white color change due to transient ischemia) of the areola with cold exposure (arrow).
Figure 2. Differences in the quality of pain described in patients with milk let-down pain vs Candida mastitis vs Raynaud phenomenon of the nipple.
Barrett ME, Heller MM, Fullerton Stone H, Murase JE. Raynaud Phenomenon of the Nipple in Breastfeeding MothersAn Underdiagnosed Cause of Nipple Pain. JAMA Dermatol. 2013;149(3):300-306. doi:10.1001/jamadermatol.2013.1560
Author Affiliations: University of Southern California, Keck School of Medicine, Los Angeles (Ms Barrett); Transitional Year Medicine Program, Harbor-UCLA, Torrance, California (Dr Heller); Department of Dermatology, Emory University, Atlanta, Georgia (Dr Heller); Menlo Dermatology Medical Group, Menlo Park, and Department of Dermatology, Stanford University Medical Center, Stanford, California (Dr Fullerton Stone); and Departments of Dermatology, Palo Alto Foundation Medical Group, Mountain View, and University of California, San Francisco (Dr Murase).
Objective To elucidate the diagnostic criteria of Raynaud phenomenon of the nipple that will aid in recognizing and treating Raynaud phenomenon in breastfeeding mothers with chronic deep nipple pain during lactation.
Design Retrospective review of a patient database composed of 22 cases of breastfeeding mothers who fit the diagnostic criteria for Raynaud phenomenon of the nipple.
Setting Menlo Dermatology Medical Group in Menlo Park, California, an academic-affiliated, private dermatologic referral center.
Patients All patients diagnosed as having Raynaud phenomenon of the nipple evaluated from January 1, 2004, through December 31, 2010.
Main Outcome Measures The rate of failed treatment for Candida mastitis, the rate of improvement of symptoms with nifedipine use, and the overall rate of improvement of symptoms with appropriate therapy involving treatment of Raynaud phenomenon.
Results Among the 22 patients with Raynaud phenomenon of the nipple, previous treatment for Candida mastitis with oral or topical antifungals was ineffective in 20 (91%). Of the 12 patients who tolerated a trial of nifedipine, 10 (83%) reported decreased or resolved nipple pain. All patients experienced marked improvement of symptoms with appropriate therapy involving treatment of Raynaud phenomenon.
Conclusions Most patients were treated with antifungals before presentation without resolution of nipple pain. Nifedipine appears to be an effective medication for the treatment of Raynaud phenomenon of the nipple. With appropriate management of Raynaud phenomenon, breastfeeding mothers demonstrated improvement of nipple pain. Raynaud phenomenon of the nipple should be considered in the differential diagnosis of nipple pain during lactation.
Breastfeeding offers optimal nutrition and immunologic protection for the infant, provides significant health benefits for the mother, and reinforces maternal and infant bonding.1,2 The American Academy of Pediatrics recommends that infants are exclusively breastfed for the first 6 months of life, followed by continued breastfeeding while complementary foods are introduced for 12 months or longer.1 In the United States, 75% of infants start out breastfeeding, but these rates decrease to 43% at 6 months and 22% at 12 months.3
One common reason reported by mothers for early discontinuation of breastfeeding is nipple pain. Mothers experiencing nipple pain often become discouraged and frustrated, ultimately leading to cessation of breastfeeding.4 In fact, studies5,6 report up to 96% of breastfeeding mothers experience nipple pain in the first 6 weeks post partum, and a significant proportion will consequently switch to bottle feeding. Therefore, it is important that physicians support the process of breastfeeding by diagnosing and managing the underlying cause of the nipple pain. Common causes of nipple pain include milk let-down pain, problems with infant latch-on and positioning, plugged lactiferous ducts, atopic dermatitis, allergic or irritant contact dermatitis, psoriasis, secondary infections with organisms such as Candida albicans or Staphylococcus aureus, and Raynaud phenomenon of the nipple.
Raynaud phenomenon is characterized by vasospasm of arterioles, causing intermittent ischemia, and subsequent reflex vasodilatation. Classically, an episode of vasospasm presents as triphasic or biphasic color change. Ischemia is manifested as pallor, followed by deoxygenation in severe episodes that results in cyanosis, followed by reflex vasodilatation and reperfusion manifested as erythema.7 Raynaud phenomenon can be classified as primary or secondary based on the cause. Primary Raynaud phenomenon is idiopathic, whereas secondary Raynaud phenomenon is due to an underlying cause, usually a connective tissue disorder. This article focuses on primary Raynaud phenomenon.
Raynaud phenomenon is commonly seen in the hands and feet, affecting up to 22% of women of childbearing age (21- to 50-year age group).8 Although less common, Raynaud phenomenon involving the tongue also has been reported.9 Women of childbearing age are at increased risk of developing Raynaud phenomenon because it is an exaggerated vasomotor response associated with elevated estrogen and stress. Estrogen increases smooth muscle expression of α2C-adrenoreceptors, which are associated with cold-induced constriction of cutaneous arteries.10 In addition, emotional stress provokes increased release of norepinephrine from the sympathetic nervous system, which binds to upregulated adrenergic receptors in vessel walls. Adrenergic receptors are upregulated because of chronic nerve irritation.11 Breastfeeding can be stressful, initiating a positive feedback loop. Although there are few reported cases of Raynaud phenomenon of the nipple among breastfeeding mothers, the largest series being a cohort of 12 patients, the contribution of vasoconstriction in the nipple to pain during lactation is generally thought to be missed by physicians and underreported in the literature.12
This study presents the largest case series to date of Raynaud phenomenon of the nipple. The objective is to elucidate the diagnostic criteria for Raynaud phenomenon of the nipple that will aid in recognizing and treating Raynaud phenomenon in breastfeeding mothers with chronic deep nipple pain during lactation.
We conducted a retrospective medical record review of breastfeeding mothers presenting with nipple pain and dermatitis. Only patients diagnosed as having Raynaud phenomenon of the nipple were included in this study. All patients were evaluated by one of us (H.F.S.) in the referral center for breastfeeding mothers at Menlo Dermatology Medical Group from January 1, 2004, through December 31, 2010. The institutional review board of Sequoia Hospital, a subsidiary of Dignity Health, has approved the retrospective review and follow-up survey of patients diagnosed as having Raynaud phenomenon of the nipple among patients who presented with breast and nipple pain.
Patients who met diagnostic criteria for Raynaud phenomenon of the nipple had chronic deep breast pain (in general, lasting ≥4 weeks) that responded to therapy for Raynaud phenomenon and had at least 2 of the following: (1) observed or self-reported color changes of the nipple, especially with cold exposure (white, blue, or red); (2) cold sensitivity or color changes of the hands or feet with cold exposure; or (3) failed therapy with oral antifungals.
Eighty eight nursing mothers presented with nipple pain and dermatitis during this period. Of the 88 women, 22 (25%) were diagnosed as having Raynaud phenomenon of the nipple based on these criteria. A 25-question follow-up survey was administered by telephone to those patients diagnosed as having Raynaud phenomenon of the nipple to better understand the quality of pain and symptoms experienced, the association with underlying autoimmune diseases, and the patient response to therapy with warming techniques or nifedipine, if indicated. Of the 22 women, 18 (82%) completed this survey. Of the 4 women who did not complete the survey, follow-up documented in the medical record (H.F.S.) was performed to assess overall response to treatment (Table 1 and Table 2).
Among the 22 breastfeeding mothers diagnosed as having Raynaud phenomenon of the nipple, all had seen at least 1 other health care professional before coming to us. Most patients (17 [77%]) reported that the initial onset of nipple pain occurred within the first 2 weeks post partum, 4 (18%) described pain within the first 2 months post partum, and 1 (5%) noted pain at 9 months.
In the follow-up survey of 18 breastfeeding mothers, the quality of pain (ie, the timing and duration of nipple pain in relation to breastfeeding) was further elicited. Among the 18 women surveyed, all experienced pain during breastfeeding. More specifically, 5 (28%) reported increased pain at the beginning of lactation and 13 (72%) experienced pain before, during, and after lactation. Women described a range of pain characteristics, from moderate pain to a severe sharp, shooting, or stabbing pain.
Patients with Raynaud phenomenon of the nipple are often misdiagnosed as having Candida mastitis. Among the 22 patients with Raynaud phenomenon of the nipple, previous treatment for Candida mastitis with topical or oral antifungals was ineffective in 20 (91%). Notably, in 18 (82%), at least 1 course of oral fluconazole therapy had failed. In addition, only 11 patients (50%) indicated that their infant had been previously treated with nystatin or had a history of a white coating in the mouth on the gums or tongue suggestive of thrush.
In the follow-up survey, 17 of 18 patients (94%) reported a history of cold sensitivity or color change in their hands and feet. Of the 4 patients who did not complete the follow-up survey, 3 had medical record–documented cold sensitivity or color change in their hands and feet. In total, 20 of 22 patients (91%) met this criterion.
Raynaud phenomenon is sometimes associated with underlying autoimmune diseases, specifically connective tissue disorders, such as lupus and scleroderma, and is then referred to as secondary Raynaud phenomenon. On questioning the patients regarding their medical history, 2 patients (11%) had a history of autoimmune disease, 1 with lupus and Sjögren syndrome and 1 with celiac disease. These were the only patients who had a known positive antinuclear antibody test result; all other patients documented a negative or unknown antinuclear antibody test result. Raynaud phenomenon of the nipple also has been correlated with previous breast surgery. Of note, 2 patients (11%) reported a history of breast surgery, including cyst removal and benign lump excision.
As previously described, all 22 patients met at least 2 of the 3 diagnostic criteria. Classically, the diagnosis of Raynaud phenomenon of the nipple is characterized by identifying biphasic or triphasic color change of the affected tissue (Figure 1). Color change of the nipples was noted in only 14 of the 22 patients (64%) diagnosed as having Raynaud phenomenon. Interestingly, of these 14 patients, 8 met all 3 diagnostic criteria, with noted color change or cold sensitivity of their acral surfaces plus failed oral antifungal therapy. In the remaining 8 patients who did not have reported or observed color change of the nipple, previous oral therapy for Candida mastitis had failed and all had reported cold sensitivity or color change of acral surfaces.
On physical examination, all 22 patients had engorged breasts, with mild to moderate erythema of the areola. Twenty patients (91%) had desquamation involving 1 or both nipples, and 2 (9%) patients had plugged lactiferous ducts.
All 22 patients were prescribed a low- to middle-strength topical corticosteroid, such as desonide ointment, hydrocortisone butyrate cream, or alclometasone diproprionate cream applied twice a day for 2 weeks. In addition, all 22 patients were advised to apply petrolatum- and lanolin-based emollients 2 to 3 times a day over the prescription topical corticosteroid and in the evening. All but 2 patients (91%) were given a standard course of oral fluconazole, consisting of 400 mg orally on day 1 and then 200 mg orally on days 8 through 10. Of the bacteria cultures performed on 9 patients, 2 yielded S aureus, and these patients were prescribed a course of oral antibiotics. The remaining 7 cultures yielded mixed skin flora.
In addition to the therapy prescribed, all 22 women were given appropriate treatment and counseling for Raynaud phenomenon of the nipple. All 22 women were given the following recommendations: (1) wear warm clothing, (2) take hot showers twice daily before breastfeeding, and (3) avoid caffeine and vasoconstrictive drugs to prevent precipitation of vasospasm.
Of the 22 women, 15 (68%) were prescribed the vasodilator nifedipine, a calcium channel blocker used for the treatment of Raynaud phenomenon. Among the 15 patients prescribed nifedipine, 6 (40%) reported experiencing common adverse effects, including dizziness, headaches, decreased blood pressure, lightheadedness, and nausea from nifedipine use, 3 (20%) of whom discontinued nifedipine use. Of the remaining 12 patients who continued nifedipine use, 10 (83%) reported decreased or resolution of pain. Reported duration of nifedipine use varied widely, from 2 weeks to 2½ years, with most citing a few months. Cessation of breastfeeding and seasonal changes were noted as reasons for stopping therapy. In addition, a few mothers self-reported repeat use with their subsequent children. All patients reported marked improvement of symptoms with multifactorial therapy involving treatment of Raynaud phenomenon of the nipple and were able to continue breastfeeding.
Patients with a history of atopic dermatitis, psoriasis, and other chronic inflammatory skin conditions have an increased risk of developing painful nipple dermatitis, secondary infections with organisms such as C albicans and S aureus, and other serious complications when breastfeeding.13 Despite therapy for the underlying inflammatory dermatoses and infection, mothers can continue to experience chronic pain during breastfeeding. Over the years, this has been given the elusive term chronic candidal mastitis, even though in many cases cultures do not detect Candida and no signs or symptoms of Candida are apparent in the mother or infant. One possible contributing factor may be the unrecognized role of vasospasm within the nipple, resulting in pain.7
In this study, 88 nursing mothers were evaluated and treated for nipple pain and dermatitis during lactation. Of these patients, 22 (25%) were diagnosed as having Raynaud phenomenon of the nipple, which is comparable to the prevalence of Raynaud disease of the hands and feet in the general population of women of childbearing age (21-50 years). Notably, 20 of the 22 patients were diagnosed as having Candida mastitis and were treated with antifungals before coming to us. Furthermore, only half of the patients (11 of 22 patients) had an infant with a history of thrush. Given that estrogen and emotional stress potentiate vasoconstriction of vessels, the increased stress and female sex hormones during breastfeeding may play a role in the initiation of vasospasm and thus the initial presentation of Raynaud phenomenon during lactation.14
It is important to recognize key features in a patient's history to identify cases of Raynaud phenomenon of the nipple. One diagnostic clue may be that the patient also has Raynaud phenomenon of other body parts. A large proportion (20 of 22 patients [91%]) of the patients reported a history of cold sensitivity or color change of acral surfaces. Another diagnostic indication often associated with Raynaud phenomenon is the presence of other autoimmune diseases, especially connective tissue disorders, and previous breast surgery.15,16
In addition, it can be useful to understand differences in the quality and timing of pain seen with Raynaud phenomenon of the nipple compared with other types of lactation pain (Figure 2). Among the 22 patients with Raynaud phenomenon, all but 1 patient experienced breast or nipple pain within the first 6 weeks post partum. Furthermore, the mothers consistently described pain during breastfeeding, and many described pain at all times, including before and after breastfeeding. Women reported the pain as being moderate to severe and described it as “sharp,” “shooting,” or “stabbing” pain.
In contrast, mothers presenting with milk let-down pain tend to describe mild pain for the first few minutes of breastfeeding that resolves with the continuation of the feed. These women also frequently describe a recurrence of pain 12 to 15 minutes after nursing with refill. The pain generally improves during the first few weeks of breastfeeding without intervention. On the other hand, women presenting with Candida mastitis often experience a moderate burning-like pain, worse with latch-on and refill but persistent throughout breastfeeding. The pain tends to radiate from the nipple through the breast to the chest wall. These women will have notable relief within 1 to 3 days of taking oral antifungals.17 Understanding the pain profiles of these conditions can help the physician focus the patient's history in such a way to better elucidate the underlying cause of the nipple pain.
On physical examination, Raynaud phenomenon of the nipple is classically identified by biphasic or triphasic color change of the affected tissue. Although previous, though limited, literature recognizes Raynaud phenomenon of the nipple only if color change is apparent, we argue that this diagnostic criteria is too narrow for the nipple. Among our 22 patients, 14 (64%) had notable color change of the nipples and met this classic definition of Raynaud phenomenon of the nipple. Because of the natural pigmentation of the skin of the nipples, vasospasm of small vessels will be less apparent than the lighter skin of the distal extremities. In addition, identifying color change of the nipple is frequently dependent on self-reported observance. Not observing the patients during breastfeeding and variable office temperatures can influence the likelihood of witnessing vasospasm. In our study, among the 8 patients who reported color sensitivity or color change of the extremities, but not of the nipple, and in whom oral antifungal therapy had failed, 5 were prescribed nifedipine in addition to warming techniques, petrolatum application, and avoidance of vasoconstrictive substances alone. Of these 5 patients, 2 reported improvement with nifedipine use, 2 reported no change in symptoms, and 1 patient discontinued nifedipine use secondary to hypotension. Notably, all 22 women reported substantial improvement in nipple pain and were able to continue breastfeeding. The improvement in symptoms with treatment of nipple vasospasm in these patients further supports our use of broader diagnostic criteria.
As with the treatment of most eczematous dermatitis, the cause of painful nipple dermatitis in breastfeeding mothers is often multifactorial. For instance, one patient may present with a flare of atopic dermatitis, superinfection with C albicans infection, and Raynaud phenomenon of the nipple, whereas another patient may present with allergic contact dermatitis, superinfection with S aureus, and plugged lactiferous ducts. As such, treatment must address all possible contributing causes of pain. Raynaud phenomenon of the nipple is often not the exclusive reason for the nipple pain, but the vasoconstriction can be a significant contributing factor.13 If oral antibiotics and antifungals do not benefit the patient or the patient has any history of cold intolerance, the physician should consider Raynaud phenomenon of the nipple as a possible contributing factor.
When properly diagnosed as having Raynaud phenomenon of the nipple, patients with chronic breast pain can improve notably if they are advised to avoid exposure to cold temperature, use techniques to keep the breasts and nipples warm, and avoid vasoconstrictive substances, including caffeine and nicotine, that may precipitate symptoms. Nifedipine, approved by the American Academy of Pediatrics for use in breastfeeding mothers, is also an effective and safe medication for the treatment of Raynaud phenomenon of the nipple.7,18,19 In this study, nifedipine appeared to significantly improve symptoms of Raynaud phenomenon and was generally well tolerated by patients. Specifically, 10 of 15 patients (67%) prescribed nifedipine reported decreased or resolution of nipple pain. Of the remaining 5 patients, 3 discontinued nifedipine therapy secondary to adverse effects and were unable to evaluate its efficacy, and 2 noted no change in symptoms with nifedipine. However, these patients experienced symptom relief with multifactorial therapy, including warming techniques and avoidance of vasoconstrictive substances. Breastfeeding women prescribed nifedipine should be counseled on common adverse effects of nifedipine, including nausea, hypotension, tachycardia, headache, and dizziness. A trial of nifedipine sustained-release formulation should be prescribed at 30 to 60 mg/d for at least 2 weeks or until breastfeeding is discontinued. If the patient experiences common adverse effects from nifedipine, a trial of low-dose therapy at 10 mg/d may be better tolerated. Mothers should be reassured that nifedipine is transferred to breast milk in low levels, amounting to less than 5% of the maternal dose.20
In conclusion, with appropriate therapy involving treatment of Raynaud phenomenon of the nipple, all patients experienced substantial improvement of symptoms and were able to continue breastfeeding. Therefore, early recognition of Raynaud phenomenon of the nipple can help prevent premature cessation of breastfeeding due to intolerable pain so that both infant and mother can experience the health, nutritional, immunologic, psychological, and social benefits of breastfeeding.1,2
Correspondence: Jenny E. Murase, MD, Department of Dermatology, Palo Alto Foundation Medical Group, 701 E El Camino Real (31-104), Mountain View, CA 94040 (firstname.lastname@example.org).
Accepted for Publication: September 27, 2012.
Published Online: December 17, 2012. doi:10.1001/jamadermatol.2013.1560
Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Barrett, Heller, Fullerton Stone, and Murase. Acquisition of data: Barrett, Heller, Fullerton Stone, and Murase. Analysis and interpretation of data: Barrett, Heller, Fullerton Stone, and Murase. Drafting of the manuscript: Barrett, Heller, Fullerton Stone, and Murase. Critical revision of the manuscript for important intellectual content: Barrett, Heller, Fullerton Stone, and Murase. Administrative, technical, and material support: Barrett, Heller, Fullerton Stone, and Murase. Study supervision: Barrett, Heller, Fullerton Stone, and Murase.
Conflict of Interest Disclosures: None reported.
Additional Contributions: Joan Bonwood, CMA, conducted the telephone interviews and provided outstanding assistance with patient care.