NIPPLE DERMATITIS ------------------------------------------------- One of the GYNs in my group referred to me a 44 year old woman with a 2 year history of swelling, erythema and purulent drainage from the right nipple. Two weeks prior to seeing me in consultation, the nipple was biopsied and found to be negative for Paget's disease. Only a descriptive diagnosis of "spongiotic dermatitis with eosinophils" was given. During the year prior to the nipple biopsy, her GYN gave her several "cortisone" creams (including Lidex), topical antifungals (including Lotrisone), and topical antibiotics (including Vytone) without improvement. She was only using 1% hydrocortisone cream to the nipple when I saw her. The patient is otherwise healthy and on no other meds, prescription or OTC. With biopsy negative for Paget's, I was concerned the patient had developed chronic ductal colonization with bacteria and/or yeast. I cultured the exudate and empirically treated her with two weeks of amoxicillin and Diflucan. Fungal and bacterial cultures grew Candida and normal skin flora. Within ten days of amox and Diflucan her problem cleared. However, when the meds ran out, the drainage and rash recurred. Her GYN restarted the amoxicillin without improvement. Retreatment with Diflucan 200mg/day controls the problem. Questions: 1. Has anyone ever seen this problem before? 2. I'm still concerned about Paget's. Should I recommend another biopsy? 3. Any other diagnoses and treatment recommendations? Thanks in advance for your help. Best regards, Joseph Yohn, MD -------------------- I would try itraconazole as it stays around longer-and check her significant other's (child, spouse) oral mucosa-maybe even treat empirically! I am one of those who treats the partners incognito yeast. Diane Thaler -------------------- I have not seen this problem. A mammogram and routine breast exam are = indicated, though.Can't help but be suspcious that something else is = going on here and not a primary candida infection. Ultrasound might help = if mammogram is normal. Further bx would be indicated if above eval is = normal and condition does not remit with several weeks of Fluconazole. = May require a deeper bx to get beyond nipple into breast at this site. I = would talk to a surgeon. Jerry Eisner -------------------- I have a similar patient with a 10-year history of bilateral nipple eczema who also has terrible atopic dermatitis and a history of recurrent methicillin-resistant Staph Aureus infections. Recently I was able to get her totally clear except her nipples. Bilateral nipple biopsies showed only eczema. She plans to get them cut off to get rid of the chronic drainage and pain. I'm also watching for more replies on this one. Gene Sienkiewicz, M. D. -------------------- A common problem for all of us who care for those individuals with atopy. Excluding Paget's, how about any unsuspected contact problem...a bra, clothes, something else that rubs in a jacket,i.e., a wallet? Would Rifampin help? Let us know how you do, or if you have any magic. Elliot Puritz -------------------- I like your suggestions but wouldn't long term low dose antibiotics (cloxacillin/ clindamycin) eventually predispose to resistant strains later on? This is certainly contradictory to what we learn from medical microbiology. Check drug history. Henry Foong MRCP -------------------- One thing to discuss is "What do you wash your nipples with?" -- this is a trick question, because ANY kind of soap is the WRONG kind of soap. She should wash with PLAIN WATER AND HER BARE HANDS. NO soap, shampoo, bubble bath, washcloths, loofa sponges, etc. etc. I explain that: "If you could have washed this problem away you wouldn't be here today!" And I explain that excessive washing removes all the natural oils that are necessary to PROTECT that delicate tissue. The same advice often is helpful for perianal pruritus and itchy perineum. I explain: "I see lots of people who start to itch and their first thought is: 'O my God, I've got to wash more!' The more they wash, the worse they get. The worse they get, the more they wash. Then they come in here and I get paid a bunch of money to tell them to stop washing so much!" I give them Loprox cream with 1% HC, to apply after washing and prn. * this locks in the moisture * Loprox has a good antibacterial and antifungal spectrum * Loprox has some anti-inflammatory effect * The 1% HC also has anti-inflammatory effect I recall a study maybe 10 years ago where someone demonstrated using skin cultures that excessive washing INCRESED the yield of pathogens after several days - presumably by inducing irritant dermatitis which subsequently got infected. Kevin C. Smith MD FRCPC -------------------- Thanks to everyone for all the thoughtful suggestions. I should clarify that the entire areolar regions are affected in my patient. She was cleared of her Staph colonization with IV Vancomycin and Nasal Bactroban - finally cultured negative from nose, breast, axillae, and perineum. At the time this was instituted she had multiple weeping impetiginized areas all over her body. She works as a food handler in school cafeteria. I also had her on the pediatricians' regimen of dilute Clorox baths (1/4 to 1/2 cup Clorox plus one packet of Aveeno Oilated Oatmeal Bath Powder per tub of water) q. d. for 10 mins. Anyway, I agree with K. Smith that long-term antibiotics are a bad idea. Her patch tests were all negative (Tru-test series). Right now I have her on Temovate Cream to the areolae for two weeks to see if I can clear the nipples even temporarily. She washes with Aquanil and wears soft cotton bras with Telfa pads absorb drainage. I'll look into the Prolactin, but there has been no galactorrhea and she is on no meds except Zyrtec 30 mg. per day and Cutivate Ointment prn. Gene Sienkiewicz, M. D. -------------------- Chronic Nipple Eczema/Discharge on Chronic Antibiotics I acknowledge your concern for development of resistant strains. But, practically speaking, I haven't had the problem with my patients and most of these chronic eczema/atopics require it to stay clear. I also check sensitivities before placing patient on antibiotic to use one that is appropriate. I don't know if these cases have some type of 'killing' deficiency or what: maybe adding zinc [Ely?Shelley?] would help? But I've had to use long term treatment no matter what. Good question/ and I am concerned. After reading all you've done today: I would add one little treatment- PUVA and treat her like a generalizing atopic with autosensitization. -- Patrick Carrington -------------------- the idea of yeast came up in the course of the discussion, but I never brought it up because I was never able to find any. My micro lab reports Candida routinely on wound swabs if it is present, and there simply hasn't been any. I am reluctant to treat with Sporanox empirically with no documentation. Gene Sienkiewicz, M. D. -------------------- The "certified lactation consultants" still insist that my patient who is breastfeeding uncomfortably has candida in the ducts. Would any of you empirically treat her with any of the po azoles while breastfeeding. Diane Thaler -------------------- I would not treat empirically without culture or KOH data. If you used anything, I would recommend considering Nystatin. Safe and I believe has been given to numerous babies over the years. Might check with a pediatrician. Overall, I don't believe the Candida theory and would not treat empirically. Jerry Eisner -------------------- Oh yeah, I also believe that terbinafine is better against candida than is typically recognized. There is at least one report which gives a cure rate for candida parapsilosis onychomycosis of around 90% (I'll dig the reference up if asked). Mark Ling, M.D., Ph.D. -------------------- Hey wait: a couple questions: terbinafine is certainly fungicidal, not static in vitro: it's the azoles which are static. Second, where is the information regarding terbinafine and tumorigenicity!? At the VERY least, it's a Category B drug re pregnancy, with no demonstrable animal teratogenicity, unlike the azoles which are Category C. I worry that an anecdotal forum like this one may start rumors which are negative and unjustified. While I certainly may be wrong about these issues, and would be happy to be corrected by Dr. Reed, I'd hope that before we site negative features of drugs we make sure our homework has been done, and ideally give references as well. Mark Ling, M.D., Ph.D. -------------------- My chief had a patient with chronic dermatitis of the nipple region, in which the biopsy showed an "eosinophilic spongiosis". Never cleared with anything. A year later, she developed pemphigus, although the initial biopsy had no hint of such a disease on recuts. This may be from way out in left field, but have you done an immunofluorescence? Warren Winkelman, MD, FRCPC -------------------- Re: Chronic Nipple Discharge/Eczema Tough problem but there are some suggestions, most of which I'm sure you've done. [1] Patch test- R/O steroid/preservative/paragen sensitivity. [2] Bacterial C&S from anterior nose, crural areas, and sacral crease. [3] Place on either Dicloxacillin or Clindamycin for routine dose only to halve dose for chronic period of time, e.g., Dicloxacillin 500 QID X 3 weeks then BID X 3-4 months. [4] Consider adding Rifampin for 10 days every 3 weeks as a cycling dose. [5] Consider either NO BRA or coton bra washed in Dove bar soap shavings with no Bounce in dryer. [6] Assuming mammogram AND cytology of any discharge is negative: r/o intraductal papillary adenoca of breast. [7] Bactroban to nose, crural areas, and sacral crease during course of antibiotics QID [which means patient will use it probably BID at most]. [8] Warm saline compresses to eczematous skin QID X 4 weeks. [9] I await other suggestions on line. -- Patrick Carrington, M.D. -------------------- Chronic nipple discharges with trigger eczematous eruptions in suitable patients. Treating the rash fixes it but it recurs soon if the d/c isn't addressed. I'd check prolactin and do a drug history for those that can cause d/c's (eg some psychotropics). Adenosis/adenomas can also do the same thing. Guy Webster -------------------- I'm not sure I understand "no hint of such a disease..." A histopath of eosiniphilic spongiosis may be a sign of pemphigus (as well as bullous pemphigoid, insect bite, contact dermatitis or incontinentia pigmenti). Steve Feldman, MD -------------------- Thanks for info, esp with respect to tumorigenicity in mice. Don't mean to dispute your ref re candida albicans, thought you were referring to a broader spectrum of organisms. Learn something every day here! Mark Ling, M.D., Ph.D. -------------------- Re the questions on terbinafine, points to be made: Dr. Reed is absolutely correct, that at currently utilized doses, terbinafine is static, not cidal versus Candida albicans. It should be realized that there is still evidence of efficacy: some is unpublished but there are references to this in the July, '96 issue of Skin and Allergy News, quoting Nardo Zaias about studies with topical terbinafine versus topical clotimazole for cutaneous candidiasis, with a 65% cure rate with terbinafine vs. 41% with clotimazole. Regarding the question of other yeasts, terbinafine has been shown to be fungicidal versus candida parapsilosis, which is in my experience by far the commonest yeast seen in the DSO pattern of onychomycosis, producing a cure rate of 85% in fingernails abd 68% for toenails (mycologically): reference Segal, Cividalli and Kritzman, Proceedings of the SEcond Annual International Summit on Cutaneous Antifungal Therapy, 11/94, Boston, MA. Finally regarding the issue of tumorigenicity, the package insert refers specifically to the development of liver tumors in rats, males only, at a dose of 13.8 times the max. reccomended human dose based on body weight. Furthermore, this was not seen in any other species, including mice, dogs and monkeys, or in vitro with human hepatocytes. It appears to be a species-specific result not of drug tumorigenicity, but of induction of peroxisomes, a rat-specific event. Multiple in vitro and in vivo assays of mutagenicity were negative, with no tumor-initiating or cell-proliferating effects. Studies in pregnant animals at doses up to 60 times max human dose showed no impairment on fetal development or fertility or spont. abortion rates. Drug of course is not recommended for pregnant or nursing mothers. I would never advocate its use in either setting, although still it's more comforting should inadvertant use in one of my patients occur that it is category B, unlike the azoles which are Cat. C. Mark Ling, M.D., Ph.D. -------------------- Even though terbinafine is FDA Pregnancy Category B, remember that this might still mean it has not been tested in humans. Category B means either safe in animals and no human testing, or safe in humans despite problems in animals. So, thalidomide *could* have had a Category B rating, if ratings had been available in the 1950s, since it had not shown any problems in animals. Just a little food for thought. Use of terbinafine is not recommended by the manufacturer during pregnancy, primarily because antifungal treatment is usually elective. It came as a surprise to me that Category B drugs might in fact be contraindicated during pregnancy. Read the find print on ibuprofen, and other NSAIDs: there is an association with premature closure of the ductus arteriosus in animals (ref: Momma K, Takao A. Transplacental cardiovascular efects of four popular analgesics in rats. Am J Obstet Gynecol 162:1304-10, 1990) and with oligohydramnios in humans (Hendricks SK, Smith JR, Moore DE, Brown ZA. Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour. Br J. Obstet Gynecol 97:312-6, 1990; Wiggins DA, Elliott JP. Oligohydramnios in each sac of a triplet gestation caused by Motrin--fulfilling Koch's postulates. Am J Obstet Gynecol 162:460-1, 1990.) The issue of what may be used in lactation is somewhat complex. Since the PDR is the reference of which most patients (and lawyers) are aware, I base my most conservative advice on that (PDR) despite the fact that it is written by and paid for by the drug company. FDA Category B doesn't relate to lactation, only pregnancy. I liken it to the SPF relating only to UVB protection, not UVA. Terbinafine is excreted in breast milk, and use is not recommended during lactation by the manufacturer. A list of drugs which may and may not be used during lactation is provided by the American Academy of Pediatrics, which last published its update in January 1994 (J Pediatrics, 93:127-50), but terbinafine was not available at the time of the last printing, and the next one will not be for about 2 years. Barbara R. Reed, MD -------------------- Yes to again echo the point, I would NEVER advocate use of terbinafine in either pregnancy or lactation! Cat. B drugs by definition are NOT shown safe for human use in pregnancy, all it says is that animal experience fails to show teratogenicity, etc. Mark Ling, M.D., Ph.D. -------------------- Ketoconazole, itraconazole and fluconazole are all FDA Pregnancy Category C. This means Human studies are lacking and animal studies may or may not show risk. There is a case of oral contraceptive failure with itraconazole. (New Z J Med 106:436, 1993). The following is from an article in progress. It pretty much covers all the antifungals. Ketoconazole is associated animal teratogenicity and should not be used in first trimester, but there is some work on use of ketoconazole for treatment of hypercortisolism of Cushing's if the fetus is a female in the 3d trimester. Fluconazole has been asociated with human malformation. Itraconazole is the least likely to harm since it has no effect on steroid hormones, but still should not be used. All manufacturers advise against use during lactation. Nystatin is OK in pregnancy and lactation. Check with your OBGs locally to see if they are less scared than we are. Barbara Reed -------------------- Barbara, do you think I have done wrong all of these years by giving moms a half tab of nizoral sample to squash up in milk (it is tasteless) for thrush, instead of weeks of purple mess? Diane Thaler -------------------- I have had two patients that inadvertantly taken ketoconizole during pregnancy over the past ten years. On each occaision the manufaqcturer sent me a comprehensive list of their experience with pregnancy and ketoconizole. As of the last data I reviewed a few years ago, ther was little evidence of any birth defects on the approximately 200+ patients. My two patients did well with normal unaffected children. Gary Salenger -------------------- oral nystatin is fine for GI candida, but has no systemic absorption, and so not useful for nipple candida, I think. Michael Fetterman --------------------