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Mammary candidiasis. A breast infection difficult to handle
M. Stamatakos, K. Kontzoglou, Constantina Sargedi, Sofia Tsaknaki, M. Safioleas (Chirurgia, 103 (5): 583-586)
Case report
A 35-year-old patient mentioned recurrent pain of the right breast in the last 3 months, accompanied by swelling of the right nipple/areola and nipple secretion.
The patient was placed under antibiotic treatment of b-generation cephalosporine, after having received secretion samples. The condition of the pre-existing inflammation however did not present any improvement, thus FNA biopsy samples from the lesion were taken for culture and microscopic examination. The culture was negative for the development of aerobic or anaerobic microorganisms. On the other hand it was positive for fungus, specifically Candida spp. The patient was given fluconazole capsules, 100 mg for 15 days. Surgical excision of the inflammatory lesion within healthy borders followed. The histological examination revealed non-specific chronic inflammatory process of the right nipple/areola.
The patient is under a yearly follow-up, by clinical examinations and breast US, and does not present any signs of local recurrence.

Mammary candidosis constitutes a disease that may have a significant impact on breastfeeding baby and is usually associated with early termination of breastfeeding (1, 2). The entity is not well defined and is most often presumptively diagnosed by symptoms and signs rather than by laboratory findings. The presenting symptoms and signs are subjective and include shiny or flaky skin of the nipple/areola, burning pain of the nipple/areola, sore nipples, stabbing pain of the breast, and nonstabbing pain of the breast.
It is recommended that the breastfeeding mother have an examination by a lactation specialist or a practitioner knowledgeable on breastfeeding to evaluate her breastfeeding technique. Before physical examination, a complete history is of great significance. The history must include the use of antibiotics during labor or postpartum, prior history of cracked nipples, and the use of pacifiers and bottles by the infant (3-5). It is interesting that several studies indicated the following as risk factors: vaginal yeast infections at the time of delivery, antibiotic therapy during labor or postpartum, the use of pacifiers and breast pumps (4, 6, 7).
Early recognition and treatment for candida of the nipple and/or breast is of great importance for successful long-term breastfeeding. If diagnosis of mammary candida is established, early complications of mild nipple candidiasis can be prevented and adequate treatment can be provided. A few studies have attempted to confirm diagnosis with microbiological testing but only the prospective study by Francis-Morrill et al. has quantified signs and symptoms with sensitivity, specificity, and positive predictive values (6-8). In this study the signs and symptoms were correlated with culture results to determine the sensitivity, specifity, and negative and positive predictive values for each symptom among the ones that are mentioned above. Also, the study indicates that there is a lag between candida colonization and clinical manifestations, since in more than half of the cases the cultures were positive for candida prior to the clinically apparent disease. Burning nipple/areola pain was the most sensitive single symptom reported which concerned 83% of the cases tested as positive for candida. However, high specificity for the symptoms or signs is indispensable as well, in order to prevent a significant “false-positive” rate. The symptoms of nonstabbing pain and stabbing pain in the breast had specificities of 84% and 79%, respectively, and the signs of shiny or flaky skin of the nipple/areola had specificities of ³90%. These figures suggest that these symptoms or signs are unlikely to present in women with negative cultures. The study has shown that the positive predictive value (PPV) constitutes the most important measure for clinicians (as compared to sensitivity and specifity), especially when it is above 70% (9). This figure of PPV was described when there was a combination of shiny and flaky skin of the nipple/areola, or when either one of these signs occurred together with nonstabbing or stabbing breast pain. It was also found that the above combinations render a high probability for candida positive cultures. More simply, the more signs and symptoms a patient has, the more possible that she will have candida. Given that PPV varies among populations depending on the prevalence of colonization, when the last one is unknown, likelihood ratios of signs and symptoms of mammary candidosis reported by lactating women, could successfully be used (10).
The diagnostic importance of signs and symptoms in mammary candidosis has been well established and is beyond any doubt. However, diagnosing the entity based only on clinical manifestations may not give a complete picture; in addition, there are other diseases that are characterized by similar signs and symptoms. As a consequence, microbiologic testing of the nipple/areola skin and milk is an appropriate and essential confirmatory step and should be made more widely available. Without microbiological testing we must use excellent systematic clinical skills to achieve the presumptive diagnosis. Both nipple/areola skin and milk should be tested, because testing only the skin can lead to false negative results. It is well known, however, that candida species can not be detected with accuracy in human milk, due to inhibitory potency of lactoferrin in vitro. As a result, there is a high rate of false negative test results. Morrill et al attempted to counter the inhibition of candida growth by lactoferrin in human milk. Milk samples should be treated with iron in order to facilitate candida growth in vitro (11). This method of culturing is selective and not readily available. As a result, culturing candida is not beneficial unless specifically designed laboratory media are used to prevent the inhibitory effect of lactoferrin. It is rare to find colonization only on the nipple/areola, but there are some cases where only the milk is colonized. In these cases, the presenting symptoms occur with less significant frequency.
There are conditions with similar appearance to that of mammary candidosis. Differential diagnosis is essential and will prevent women from receiving unnecessary and inappropriate medications and nursing. Differential diagnosis of nipple pain includes the following entities: eczema, Raynaud’s syndrome of the nipples and bacterial infection. It can sometimes be problematic as nipples with any one of these conditions can appear normal. Eczema of the areola and nipple usually occurs with an acute onset of vesicular eruptions and crusting, and less often appears as a dry scaling dermatitis. It presents mainly in women with a prior history of eczema and in most of the cases does not affect the nipple. Raynaud’s syndrome is described after exposure to cold temperatures and occurs with severe, burning pain of the nipples caused by vasospasm (12). It presents with blanching of the nipples, followed by cyanosis and/or erythema (13). The presenting signs and symptoms that concern bacterial infection are red, inflamed, cracked nipples with or without exudates or fever. As far as breast pain is concerned, differential diagnosis includes: plugged ducts, mastitis, and breast abscess. Plugged ducts do not have the clinical appearance of a systemic infection and constitute localized blockage of milk. They can be, however, a trying condition for the patient. Lactation mastitis is defined as cellulitis of the interlobular connective tissue of the mammary gland. Mastitis usually occurs after the first 10 days postpartum but can also be evident any time during the breastfeeding period; its incidence varies from 2,5% to 24% (14,15). Diagnosis is established with the presence of fever, malaise and flulike symptoms. The area of the breast appears red, tender and hot. Mastitis is a localized inflammation, usually unilateral, and may involve a bacterial organism. The development of bacteria comes, in most cases, as a result of inadequate removal of milk, and mainly concerns staphylococcus aureus (40% of cases) (16). Staphylococcus aureus is supposed to penetrate in the breast tissues through a cracked, impaired nipple (15). Breast abscess occurs as a serious complication in approximately 3% to 11% of mastitis infections (17, 18). The main reason for their formation is the delayed and inappropriate administration of antibiotics. Due to their problematic clinical diagnosis, abscesses are often detected by ultrasonography (18). As breast and nipple pain is a common feature of mammary candidosis, it often leads to early termination of breastfeeding. That is why prompt and adequate treatment is of vital importance in supporting successful long-term breastfeeding. The pharmacologic treatment of candida of the nipple and ductal system is indefinite because of the absence of medical protocols and guidelines; for this reason a conservative approach to prescribing medications is suggested. Treatment of nipple candida must include the simultaneous treatment of the breastfeeding child. The most common treatment for the baby is oral nystatin combined with oral fluconazole (5, 19). As for the mother, the most widely recommended treatment for localized candida of the nipple is an antifungal, topical medication such as Nystatin (Mycostatin) (1, 3, 5,). It has been observed, however, that more than 40% of yeasts are resistant to Nystatin. Because of this data, miconazole or clotrimazole creams are used to treat the mother. The therapeutic management often includes a topical antibiotic ointment; for fear that nipple fissures simultaneously occur. In such cases the main etiologic factor is Staphylococcus aureus and either mupirocin or Neosporin can be prescribed (12, 20). A mid- or low-potency topical steroid cream can be used additionally, especially when the nipples appear significantly red and inflamed (21).
Persistent cases of nipple yeast or presumptive ductal yeast are currently treated with oral fluconazole, in doses similar to those that have been used for candidiasis infections in other organs (3, 5, 22-24). However, fluconazole is not approved by the Food and Drug Administration for mammary candidosis. The administration of fluconazole continues for 1 to 2 weeks after symptoms have resolved to avoid relapse. It is recommended that breastfeeding continue during the administration. It is important though, for the physician to inform properly and with a high sense of responsibility the nursing mother. The available data about this medication is inadequate and the mother herself must weigh the benefits and risks. Also, consultation is essential before prescribing fluconazole to women who are on other medications. The medication has drug to drug interactions and increases plasma levels of phenytoin, warfarin, cisapride, and some sulfonylureas.

Primary breast fungus disease is an extremely rare clinical condition. In order to reach an accurate diagnosis a detailed history and clinical examination are necessary. Both nipple skin and milk secretion samples need to be tested for the results to be reliable. Differential diagnosis can help women to avoid inappropriate medication receipt. The treatment includes both local antifungal creams for the mother and oral antifungal agents for the breastfeeding baby. Careful follow-up is demanded in order to prevent complications such as bacterial over-infection or ductal expansion of candida.

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2. Schartz, K., D’Arcy, H.J., Gillespie, B., Bobo, J., Longeway, M., Foxman, B. - Factors associated with weaning in the first 3 months postpartum. J. Fam. Pract., 2002, 51:439.
3. Porter, J., Schach, B. - Treating sore, possibly infected nipples. J.H. Lact, 2004, 20:221.
4. Dinsmoor, M.J., Viloria, R., Lief, L., Elder, S. - Use of intrapartum antibiotics and the incidence of postnatal maternal and neonatal yeast infections. Obstet. Gynecol., 2005, 106:19.
5. Brent, N.B. - Thrush in the breastfeeding dyad: Results of a survey on diagnosis and treatment. Clin. Pediatr., 2001, 40:503.
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8. Francis-Morrill, J., Heinig, M.J., Pappagianis, D., Dewey, K. - Diagnostic value of signs and symptoms of mammary candidosis among lactating women. J. Ham. Lact., 2004, 20:288.
9. Grimes, D.A., Schulz, K.F. - Uses and abuses of screening tests. Lancet, 2002, 359:881.
10. Brenner, H., Gefeller, O. - Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence. Stat. Med., 1997, 16:981.
11. Morill, J.F., Pappagianis, D., Heinig, M.J., Lonnerdal, B., Dewey, K.G. - Detecting Candida albicans in human milk. J. Clin. Microbiol., 2003, 41: 475.
12. Amir, L., Garland, S., Debberstein, L., Farish, S. - Candida albican: Is it associated with nipple pain in lactating women? Gynecol. Obsetet. Invest., 1996, 41:31.
13. Anderson, J.E., Held, N., Wright, K. - Raynaud’s phenomenon of the nipple: A treatable cause of painful breastfeeding. Pediatrics, 2004, 113:360.
14. Foxman, B., D’arcy, H., Gillespie, B., Bobo, J.K., Schwartz, K. - Lactation mastitis: Occurrence and medical management among 946 breastfeeding women in the United States. Am. J. Epidemiol., 2002, 155:103.
15. Mass, S. - Breast pain: engorgement, nipple pain and mastitis. Clin. Obstet. Gynecol., 2004, 47:679.
16. Amir, L., Forster, D., McLachlan, H., Lumeley, J. -Incidence of breast abscess in lactating women: Report from an Australian cohort. Br. J. Obtet. Gynaecol., 2004, 111: 1378.
17. Deber, C., Inan, A. - Breast abscesses in lactating women. World J. Surg., 2003, 27:130.
18. Ulitzsch, D., Nyman, M., Carlson, R. - Breast abscess in lactating women: US-guided treatment. Radiology, 2004, 232:904.
19. Goins, A., Ascher, D., Waecker, N., Arnold, J., Moorefield, E. - Comparison of fluconazole and nystatin oral suspensions for treatment of oral candidiasis in infants. Pediatr. Infect. Dis. J., 2002, 21:1165.
20. Graves, S., Wright, W., Harman, R., Bailet, S. - Painful nipples in nursing mothers: Fungal or staphylococcal? A preliminary study. Aust. Fam. Physician, 2003, 32:570.
21. Okutomi, T., Abe, S., Tansho, S., Wakabayashi, H., Kawase, K., Yamaguchi, H. - Augmented inhibition of growth of Candida albicans by neutrophils in the presence of lactoferrin. Immunol. Med. Microbiol., 1997, 18:105.
22. Hale, T. - Medications and mother’s milk. Amarillo (TX): Pharmasoft, 2004.
23. Sobel, J.D., Kauffman, C.A., McKinsey, D., Zervos, M., Vanquez, J.A., Karchmer, A.W., Lee, J., Thomas, C., Panzer, H., Dismukes, W.E. - Candiduria: a randomized double-blind study of treatment with fluconazole and placebo-controlled trial. Clin. Infect. Dis., 2000, 30:19.
24. Wainer, S., Cooper, P.A., Gouws, H., Akierman, A. - Prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr. Infect. Dis. J., 1997, 16:763.

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