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Pregnancy-Associated Hyperkeratosis of the Nipple a Report of 25 Cases

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Pregnancy-Associated Hyperkeratosis of the Nipple a Report of 25 Cases OBSERVATION Pregnancy-Associated Hyperkeratosis of the Nipple A Report of 25 Cases H. William Higgins, MD; Jennifer Jenkins, MD, MPH; Thomas D. Horn, MD, MBA; George Kroumpouzos, MD, PhD Importance: Reported physiologic nipple changes in symptomatic aggravation only during pregnancy or breast- pregnancy do not include hyperkeratosis and are ex- feeding. The lesions persisted post partum in 22 pa- pected to resolve or improve post partum. Hyperkerato- tients (88%). Histopathologic features were conspicu- sis of the nipple and/or areola can develop in the con- ous orthokeratotic hyperkeratosis, with papillomatosis text of inflammatory diseases (such as atopic dermatitis), and acanthosis being mild or absent. in acanthosis nigricans, as an extension of epidermal ne- vus, after estrogen treatment, and/or in nevoid hyper- Conclusions and Relevance: Pregnancy-associated hy- keratosis of the nipple and areola. We performed a clini- perkeratosis of the nipple can be symptomatic and per- copathologic analysis of cases of pregnancy-associated sist post partum. It may represent a physiologic change nipple hyperkeratosis. of pregnancy. The characteristic clinicopathologic fea- tures of this disorder allow differentiation from nevoid Observations: Twenty-five cases of pregnancy- hyperkeratosis of the nipple and areola. We suggest that associated nipple hyperkeratosis identified during a 5-year this distinctive clinicopathologic entity be called preg- period (January 1, 2007, through December 31, 2012) nancy-associated hyperkeratosis of the nipple. are reported. The lesions were bilateral and involved pre- dominantly the top of the nipple. Lesions were sympto- matic in 17 patients (68%), causing tenderness or dis- JAMA Dermatol. 2013;149(6):722-726. comfort, pruritus, sensitivity to touch, and/or discomfort Published online April 24, 2013. with breastfeeding. Nine patients (36%) experienced doi:10.1001/jamadermatol.2013.128 HYSIOLOGIC CHANGES OF THE bilateral.9 Kubota et al8 reviewed 45 HNA nipple and areola during cases and found that 58% of cases in- pregnancy include enlarge- volved both the nipple and areola, 25% ment, hyperpigmentation, only the areola, and 17% solely the nipple. secondary areolae, erectile Although HNA can worsen, become bi- Pnipples, prominence of veins, striae, and lateral in pregnancy, or both,10,11 onset dur- enlargement of the Montgomery glands or ing or immediately after pregnancy has tubercles (hypertrophied sebaceous been only exceptionally reported.5,9-13 It has glands).1,2 In addition, benign tumors, such been postulated that endocrine factors may as seborrheic keratoses, skin tags, and be involved in the etiopathogenesis of HNA Author Affiliations: warts, can develop on the nipple during because the lesions worsen in pregnancy Author Aff Department of Dermatology, gestation. Furthermore, the nipple can be and have been associated with estrogen Departmen The Warren Alpert Medical affected in pregnancy by diseases, such as therapy.8,14 The Warren School of Brown University, 3 School of B Providence, Rhode Island atopic dermatitis, and other conditions as- In this case series we describe 25 patients Providence (Drs Higgins and sociated with hyperkeratosis of the nipple with pregnancy-related hyperkeratosis of the (Drs Higgin Kroumpouzos); Division of and areola (HNA), such as acanthosis ni- nipple. We discuss the distinctive clinico- Kroumpouz Dermatology, Dedham Medical gricans, ichthyosis, and Darier disease.4,5 pathologic features, differentiation from Dermatolog Associates, Atrius Health, The idiopathic form of HNA is reported other entities (such as HNA), postpartum Associates, Dedham, Massachusetts 6 Dedham, M (Dr Jenkins); Departments of as nevoid HNA. More than 70 cases of prognosis, and treatment. (Dr Jenkins 7 Dermatology and Pathology, HNA have been reported. Although HNA Clinical and histopathologic data were Dermatolog Massachusetts General is typically diagnosed in females between obtained from a medical record review of Massachuse Hospital, Harvard Medical puberty and the third decade of life, it has cases that were seen during a 5-year pe- Hospital, H School, Boston (Dr Horn); and been exceptionally reported in males re- riod (January 1, 2007, through December School, Bos South Shore Medical Center, 8 South Shor Atrius Health, Norwell, ceiving hormonal treatment. The le- 31, 2012) in a dermatology clinic of a health Atrius Heal Massachusetts sions of HNA are confluent and verru- system. Documentation included photog- Massachuse (Dr Kroumpouzos). cous, and their distribution is usually raphy of lesions; medical, family, and ob- (Dr Kroum JAMA DERMATOL/ VOL 149 (NO. 6), JUNE 2013 WWW.JAMADERM.COM 722 ©2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Table. Clinical Findings of the Study Patients Affected/ Postpartum Patient No./ Dermatologic Total Duration and Age, ya Involvementb Findings Symptoms Pregnancies Course, yc Treatment 1/38 Focal Focally warty, pink or yellow, Sensitive to touch 3/3 9 12% Ammonium lactate fissured papules cream (MDR) 2/34 Focal Focal, warty, pink or yellow No 2/2 6 Emollients (MR) papules 3/32 Diffuse Mildly hyperkeratotic, focally Tenderness or discomfort 4/4 14 Low-potency topical warty, fissured, inflamed steroids (MR) papules 4/31 Diffuse Mildly warty, minute papules Sensitive to touch 2/2 10 Emollients (MR) 5/29 Focal; areola less Mildly hyperkeratotic, yellow Mildly pruritic 2/2 2 0.025% Tretinoin cream affected papules after second pregnancy (MDR) 6/33 Diffuse Moderately hyperkeratotic, yellow, Pain during breastfeeding 2/2 (1 twin) 12 Low-potency topical confluent, fissured papules steroids (MR) 7/29 Focal; RϾL Moderately hyperkeratotic, yellow, Mild tenderness or 3/3 (1 twin) 25 12% Ammonium lactate inflammatory papules discomfort cream after last pregnancy (MDR) 8/31 Diffuse Mildly hyperkeratotic, tan papules No 3/3 Improved after None breastfeeding 9/35 Diffuse; areola Moderately hyperkeratotic, yellow, Mildly pruritic 2/2 Improved prior None less affected inflammatory papules to breastfeeding 10/31 Diffuse Warty, pink or yellow papules Tenderness or discomfort 1/1 24 None during breastfeeding 11/32 Diffuse Mildly warty tan papules No 1/1 1 Emollients (MR) 12/29 Diffuse Mildly warty, pink to yellow Tenderness or discomfort 1/1 (twin) Spontaneous pp None papules in pregnancy improvement 13/32 Diffuse; RϾL Moderately hyperkeratotic, yellow, Tenderness or 2/2 14 y; worse Curettage (CR) confluent, fissured papules discomfort, during 2nd breastfeeding pregnancy difficulties 14/29 Diffuse Mildly warty, tan papules No 3/3 (1 twin) 9 None 15/30 Diffuse Moderately hyperkeratotic, yellow Mild tenderness or 3/8 (3 full term) 13 y; worse with Emollients (NR) papules discomfort with each full-term breastfeeding pregnancy 16/31 Focal, well Warty, yellow papules Mild tenderness or 1/2 (1 full term) 4 y; worse with 0.025% Tretinoin cream demarcated discomfort during full-term (MR) breastfeeding pregnancy (did not breastfeed) 17/23 Focal, well Warty, yellow papules Mild tenderness or 1/1 10 Emollients (MR) demarcated discomfort in pregnancy 18/37 Focal Moderately hyperkeratotic, yellow Tenderness or discomfort 2/2 5 Emollients (MR) papules during breastfeeding of first child 19 /24 Focal Moderately hyperkeratotic, yellow No 3/3 17 None papules 20/34 Focal Moderately hyperkeratotic, tan, No 2/2 10 None confluent papules 21/42 Focal Focally hyperkeratotic, tan papules Tenderness or discomfort 1/2; lesions in 2 Lanolin-based emollient during breastfeeding 2nd pregnancy (NR) 22/25 Focal Mildly hyperkeratotic, yellow Tenderness or discomfort 3/3 17 Lanolin-based emollient papules during breastfeeding (NR) 23/36 Focal; RϾL Mildly hyperkeratotic, tan papules No 1/1 1 None 24/22 Focal Warty, yellow papules No 1/1 8 None 25/31 Focal; LϾR Mildly hyperkeratotic, yellow Sensitive to touch 2/3 (2 full term) 16 12% Ammonium lactate papules cream (MDR) Abbreviations: CR, complete response; MDR, moderate response; MR, mild response; NR, no response; pp, postpartum. a Age of patient at presentation. b Symmetric, unless otherwise noted. c Persisted post partum, unless otherwise noted. stetric history; postpartum course; and treatment. Pa- REPORT OF CASES tients’ response to treatment was rated by the physician as none (absence of any improvement), mild (minimal im- provement), moderate (satisfactory response), and com- Twenty-five patients, aged 23 to 42 years, presented with plete (resolution of lesions). Nine patients underwent his- hyperkeratosis of the nipple in association with preg- topathologic examination of the lesions. The study was nancy (Table). Twenty patients (80%) developed the le- determined to be exempt from institutional review board sions in the second or third trimester and 3 patients (12%) review by the Harvard Pilgrim Health Care Human Stud- in the first trimester. In the remaining 2 patients, the le- ies Committee. sions were noticed by the physician post partum, but pa- JAMA DERMATOL/ VOL 149 (NO. 6), JUNE 2013 WWW.JAMADERM.COM 723 ©2013 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 tients had noticed their onset in the third trimester. All reported tenderness, and 1 patient (4%) reported im- cases showed bilateral, predominantly symmetric in- provement with breastfeeding (Table). The lesions per- volvement (Figure 1A). Fourteen cases (56%) in- sisted post partum in 22 patients (88%). Persistence of volved only focally the top of the nipple
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