Periocular hypopigmentation of the elderly: A new POTUS dermatosis?

By Warren R. Heymann, MD, FAAD
Sept. 4, 2024
Vol. 6, No. 36

Editorial Note: DermWorld Insights and Inquiries provides commentaries on issues in dermatology. This editorial was composed before the assassination attempt of former President Trump, President Biden’s decision not to seek a second term, and the nomination of Vice President Kamala Harris. As anticipated, this election cycle is especially rancorous and fraught with emotion. Dermatologists, like all Americans, have different varied political opinions and preferences. DWI&I respects those differences and maintains neutrality in the spirit of equanimity for all.

As we are amid the 2024 election, this is an opportune time to review significant dermatologic disorders that afflicted several Presidents of the United States (POTUS). Mlacker et al. (1) reviewed this topic — presented in italics and interspersed with bracketed and referenced elaborations. Following the historical summary, consideration will be given to a newly named dermatosis that may ultimately be associated with other POTUS dermatoses.

American history encompasses a wide spectrum of dermatologic pathology that has affected past Presidents of the United States and their families. America’s founding father, George Washington, developed a ‘‘malignant carbuncle’’ on his left hip during his first year as president, requiring incision and drainage. James Madison developed frostbite on his nose after campaigning outside for the First Congress in 1788. A few days after delivering the Gettysburg Address, Abraham Lincoln developed ‘‘dusky red spots about the forehead,’’ which after spreading to his face and extremities, evolved into an acneiform appearance, coinciding with a smallpox epidemic. [When Lincoln delivered the Gettysburg Address, he was weak and dizzy. On the train back to Washington he was febrile, weak, and had severe headaches. On the fourth day of the illness a scarlet red rash appeared that became vesicular. The entire illness lasted three weeks. The diagnosis was “varioloid,” an old name for a mild variant of smallpox in a partially immune patient. It is not known if Lincoln was immunized against smallpox. (2)]

One of America’s Civil War heroes, Ulysses Grant, developed a cancerous growth at the base of his tongue in 1884; this occurred after many years of heavy drinking and smoking, inevitably leading to his unfavorable demise. Similarly, Grover Cleveland developed a malignancy on the left side of his jaw, involving the soft palate, and underwent a secret operation for its removal in 1893. [Because Cleveland survived for 15 years following his surgery, without postoperative radiation, the diagnosis of this being a malignancy was subsequently questioned, with some speculation that his disorder was actually necrotizing sialometaplasia. Further analysis confirmed that he had a verrucous carcinoma of the hard palate and gingiva. (3)]

In 1892, Rutherford B. Hayes developed dermatitis, involving his hands and face secondary to his exposure to poison ivy while pruning trees. Franklin D. Roosevelt’s pigmented nevus, located above his left eyebrow, no longer appeared in photographs after 1943, leading people to believe that it had been removed. The importance of this subtlety was noted after the president’s fatal seizure in 1945, raising questions regarding melanoma as the possible culprit. [I encourage you to look at the fascinating article by Ackerman and Lomazow documenting the progression of this lesion throughout FDR’s life — clinically, the lesion could have been a lentigo-seborrheic keratosis overlap or a melanoma. (4)]

John F. Kennedy was diagnosed with Addison’s disease in 1947, years before serving as president. Although Kennedy exuded vitality with his youthful, tanned-like appearance, the hyperpigmentation of his face was actually a manifestation of his autoimmune condition. Lyndon Johnson underwent a clandestine procedure in 1967 in order to remove a basal cell carcinoma from his left ankle. Similarly, Ronald Reagan had basal cell carcinomas removed both during, and in the years following his presidency; moreover, his daughter, Maureen Reagan, subsequently passed away due to systemic melanoma metastases. [Basal cell carcinomas also afflicted George HW Bush. I had the honor of informing President Bush (# 41) of this possibility after seeing his photograph on the cover of a New York Times magazine in 1986 (image). For more details read the DWI&I commentary honoring him. (5)].

Finally, it is well known that Bill Clinton has long suffered from rosacea and additionally received treatment for actinic keratosis and basal cell carcinoma. [Most recently, Joe and Jill Biden have had basal cell carcinomas removed. (6) As revealed throughout American history, dermatology can indeed have an impact on anyone’s life, including the lives of prominent political leaders.

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I was intrigued by the manuscript by Mildner et al., describing “periocular hypopigmentation of the elderly” (POHE). A total of 14 patients (age 77.0 ± 11.1 years, 8/14 [57.1%] females) were enrolled. Asymptomatic, bilateral hypopigmentation affecting both the upper and lower eyelids was observed in all patients. Patients had no periocular skin problems, although one had frontal fibrosing alopecia of the eyebrows and another had Graves’ orbitopathy. All patients had blepharochalasis, steatoblepharon and sun-damaged skin, and all were either of Fitzpatrick skin phototype II (10/14 [71.4%]) or phototype III (4/14 [28.6%]). Twelve patients (85.7%) presented with a purple hue on upper eyelids [attributed to telangiectasias] and 13 (92.9%) clinical signs of skin atrophy. Ten patients (71.4%) reported to wear sunglasses regularly, 4 (28.6%) wore spectacles, 7 (50.0%) used cosmeceuticals in their periocular area, 5 (35.7%) non-medicated eye drops and 1 (7.1%) medicated eye drops. A biopsy from one patient showed that melanocytes, melanin pigment and melanophages were all preserved but reduced as compared to non-lesional periorbital control skin. The authors propose that POHE results from a combination of external (e.g. sparing during sun exposure, surrounded by hyperpigmented and actinically damaged skin) and internal factors (e.g. fair skin types and intrinsic skin ageing), “reflecting a variant of the aesthetic norm rather than a pathological condition.” (7)

The clinical differential diagnosis includes vitiligo (including the Vogt-Koyanagi-Harada syndrome), vitiligo-like lesions due to inhibition of the c-kit pathway by imatinib, and post-inflammatory hypopigmentation following allergic contact dermatitis (as reported with olapatidine eye drops, and chloramphenicol ointment). (8,9,10,11)

I applaud Mildner et al. for putting a name on a dermatologic disorder that is likely underrecognized (although I respectfully suggest that the word “maturity” be substituted for “elderly” — from POHE to POHM). I have seen this in my patients, and I am confident that a former president’s eyes are consistent with POHE. Who do you think that is? (I do not wish to play “armchair dermatologist” based on photographs alone, so that president will remain unnamed until a proper examination confirms the diagnosis.)

Point to Remember: Periocular hypopigmentation of the elderly (POHE) is a diagnosis of exclusion after vitiligo, post-inflammatory hypopigmentation to due contact dermatitis, or medication-induced hypopigmentation are ruled out. POHE is likely due to a combination of actinic damage and intrinsic aging in those with lighter complexions.

Our expert’s viewpoint

Simon M. Mueller, MD
Leading dermatologist, University Hospital Basel
Switzerland

The periocular dermatological “paint palette” and underlying causes

The periocular region can be of particular dermatological significance as various medical conditions can manifest there in different colors: Brownish discoloration may result from pregnancy, oral contraceptives, anti-glaucoma drops (12, PMID: 35032359), internal diseases (such as kidney, liver, or thyroid disease), or post-inflammatory hyperpigmentation, for example, related to atopic eczema. Periocular redness may indicate irritant-toxic or allergic contact dermatitis to eyelid cosmetics such as mascara, eyeliner, or sunscreens (13, PMID: 27004926). Bilateral, un-sharply demarcated orange discoloration of the upper eyelids, termed “Orange palpebral spots,” is a pattern distinct from xanthelasma or carotenoderma but still of unknown etiology. Fluorescein palpebral spots can appear quite similar but can be easily washed off (14, PMID: 26267340). Necrobiotic xanthogranuloma, associated with monoclonal gammopathy, is another differential diagnosis of orange or yellowish periocular discoloration. In systemic amyloidosis, brownish-yellowish papules and plaques usually present with purpura due to the fragility of skin vessels. The heliotrope rash observed in dermatomyositis might also have a subtle yellowish appearance but is more often lilac and accompanied by swelling of the eyelids. Bilateral ecchymosis, also referred to as “raccoon/panda” eyes, may indicate severe conditions such as fractures of the base of the anterior cranial fossa, insult to the hypothalamic-pituitary axis causing endocrinopathies, or neuroblastoma among others (15, PMID: 31194384). While these colorful periocular lesions are well described, much less is known about periocular hypopigmentation apart from vitiligo. As described in our publication mentioned above, we assume that the POHE is a common but underrecognized periocular feature to complete the “paint palette.” I fully agree that POHM (“maturity” instead of “elderly”) would be a more euphemistic term and believe that the possibly affected, mentioned unnamed former (and future?) president would presumably also prefer this term.

1. Mlacker S, Aldahan A, Shah V, University of Miami, Nouri K, MD. Dermatologic ailments in the White House. J Am Acad Dermatol 2016; 74 (5):M Supplement AB28.

2. Goldman AS, Schmalstieg FC Jr. Abraham Lincoln's Gettysburg illness. J Med Biogr. 2007 May;15(2):104-10. doi: 10.1258/j.jmb.2007.06-14. PMID: 17551612.

3. Cooper PH. President Cleveland's palatal tumor. Arch Dermatol. 1986 Jul;122(7):747-8. PMID: 3524470.

4. Ackerman AB, Lomazow S. An inquiry into the nature of the pigmented lesion above Franklin Delano Roosevelt's left eyebrow. Arch Dermatol. 2008 Apr;144(4):529-32. doi: 10.1001/archderm.144.4.529. PMID: 18427048.

5. Heymann WR. 41’s gracious contribution to skin cancer awareness. Dermatology World Insights and Inquiries. December 1, 2018. https://staging.aad.org/dw/dw-insights-and-inquiries/medical-dermatology/41s-gracious-contribution-to-skin-cancer-awareness

6. https://www.npr.org/2023/03/03/1161049252/biden-skin-cancer

7. Mildner LS, Zhu J, Navarini AA, Itin P, Mühleisen B, Müller SM. Periocular hypopigmentation of the elderly (POHE): A case series. J Eur Acad Dermatol Venereol. 2024 Feb;38(2):e188-e190. doi: 10.1111/jdv.19526. Epub 2023 Oct 4. PMID: 37728534.

8. Souza Leite RM, Craveiro Leite AA. Two therapeutic challenges: periocular and genital vitiligo in children successfully treated with pimecrolimus cream. Int J Dermatol. 2007 Sep;46(9):986-9. doi: 10.1111/j.1365-4632.2007.03282.x. PMID: 17822508.

9. Llamas-Velasco M, Fraga J, Kutzner H, Steegmann JL, García-Diez A, Requena L. Hypopigmented macules secondary to imatinib for the treatment of chronic myeloid leukemia: a histopathologic and immunohistochemical study. J Cutan Pathol. 2014 May;41(5):417-26. doi: 10.1111/cup.12298. Epub 2014 Feb 26. PMID: 24467724.

10. Suchi ST, Gupta A, Srinivasan R. Contact allergic dermatitis and periocular depigmentation after using olapatidine eye drops. Indian J Ophthalmol. 2008 Sep-Oct;56(5):439-40. doi: 10.4103/0301-4738.42431. PMID: 18711283; PMCID: PMC2636135.

11. Rathod DJ, Shuttleworth GN. Anterior uveitis, poliosis, and skin hypopigmentation associated with topical chloramphenicol allergy following ptosis surgery. Ophthalmic Plast Reconstr Surg. 2007 Jul-Aug;23(4):318-9. doi: 10.1097/IOP.0b013e318073c636. PMID: 17667109.

12. Patchinsky A, Petitpain N, Gillet P, Angioi-Duprez K, Schmutz JL, Bursztejn AC. Dermatological adverse effects of anti-glaucoma eye drops: a review. J Eur Acad Dermatol Venereol. 2022 May;36(5):661-670. doi: 10.1111/jdv.17928. Epub 2022 Feb 11. PMID: 35032359.

13. Oh JE, Lee HJ, Choi YW, Choi HY, Byun JY. Metal allergy in eyelid dermatitis and the evaluation of metal contents in eye shadows. J Eur Acad Dermatol Venereol. 2016 Sep;30(9):1518-21. doi: 10.1111/jdv.13646. Epub 2016 Mar 23. PMID: 27004926

14. Mueller SM, Itin P. Of orange and yellow eyelids. Int J Dermatol. 2015 Nov;54(11):e495-6. doi: 10.1111/ijd.12912. Epub 2015 Aug 12. PMID: 26267340.

15. M Das J, Munakomi S. Raccoon Sign. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542227/

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