Frontal Fibrosing Alopecia as a result of medications
and supplements
Vidhi Shah, Colleen Reisz
UMKC School of Medicine
Introduction
Frontal fibrosing alopecia (FFA) is a form of hair loss that
affects the frontal hairline at menopause in white female patients.
FFA is typically progressive and results in irreversible scarring
and alopecia [1]. There is no reliable treatment of FFA but
steroids, anti malarials and methotrexate have been tried [2].
The disease is considered progressive although there is a
subset whose disease slows over time, regardless of treatment.
We theorized that FFA is mediated by changes in local
tissue aromatase activity affected by the use of
medications and supplements in addition to the physiologic
effects of age, body habitus, and hormonal status.
Objectives
FFA typically affects white women almost exclusively in the
frontal hairline. The incidence of FFA is increasing [1]. The onset To collect biometric and pharmaceutical data in women with
FFA for known factors that would alter aromatase.
of FFA at menopause strongly implicates a hormonal effect
although the exact mechanism is unknown [3].
To examine the effects of drug and supplement reduction (in
Estrogen synthesis shifts from the gonad to peripheral fat tissue addition to diet and exercise) on FFA.
starting in middle age, peripheral estrogen production is
controlled by local transcription factors that regulate aromatase
activity[ [4,6]. Aromatase exhibits regional and gender
differences in the scalp, with women having a 6 fold increase in
aromatase in the frontal scalp [5,6].
Methods
Age, obesity, insulin resistance and drugs impact endocrine
signaling pathways and have the capacity to up regulate
aromatase [7]. Up regulation of aromatase leads to androgen
depletion and the formation of harmful estrogen metabolites that
affect fibroblasts and macrophages [5,8,9].
Data was collected on patients presenting to a private
dermatology practice with FFA from 2011 to 2014. We
collected biometric data, drug lists, including vitamins
and supplements, Fitzpatrick phototyping and comorbid
states.
In addition to diet and exercise recommendations,
vitamin and supplements were discontinued with the
exception of vitamin D. Whenever possible, drugs
known to increase insulin resistance were discontinued
or modified to improve the insulin resistance profile.
Response to therapy was defined as reduction in
redness and scale at the follicular os and no further
progression of alopecia. Patients were categorized as
responders or non-responders.
Results
• 18 patients presented with FFA during the study interval.
One patient was not accepting of therapy and one
patient did not follow up. The remaining 16 patients are
summarized in Table 1.
• 9/18 patients who had medications adjusted along with discontinuation
of vitamin and mineral supplements responded to therapy; 6 more
have agreed to our suggestions on reduction
• 1/2 patients who were not on medications known to affect insulin
resistance or on vitamins/supplements improved with increase in
vitamin D (pt 7)
• 1 has had relentless progression and no response to treatment (pt 2)
TABLE 1. Demographic, clinical and response characteristics of 16 women with FFA
Patient
No.
Age/ age at
onset of
hair loss, y
BMI
Fitzpatrick
Co-morbid conditions
Xenobiotic
Response/Reduction
1.
62
32.00
1
-
Simvastatin, Metoprolol
Lost to follow up
2.
62/59
28.30
1
Premature ovarian failure at
42 y
-
No response
3.
58/57
22.90
1
-
V/S III
Reduction in progress
4.
75/73
34.90
2
DM II
Simvastatin
+
5.
71/69
33.30
2
-
V/S II
+
6.
68/65
24.80
2
Morgellens disease see
note
V/S III
+
7.
60/58
25.60
1
Multiple squamous cell
carcinoma of the skin
starting at menopause
-
+
8.
41/41
37.44
2
Preeclampsia II, Multiple
Sclerosis
Prednisone, Betaseron
+
9.
-
-
1
Pharmacokinetic/photosensi
tivity issues see note
V/S III
+
10.
73/73
26.07
2
-
Atorvastatin, Metoprolol,
Omeprazole, Losartan,
Tramadol, Sertraline
+
11.
65/56
25.09
1
-
V/S II
Simvastatin
+
12.
39/39
21.48
4
Triathlete with special diet,
creatine, whey, amino acids
V/S III (10)
Orsythia, Spironolactone
+
13.
58/55
22.92
3
-
V/S II
Pravastatin, Lisinopril,
Flax, Glucosamine
Reduction in progress
14.
60/58
20.50
3
Raynauds,livedo,
unclassified autoimmune
disorder
V/S II
Switch from oral to patch
estrogen
Reduction in progress
15.
72/64
33.99
1
Hair loss temporally within
one month of sertraline
V/S III
Atorvastatin, Sertraline,
Mobic, Triamterene,
Trazodone, Hydrocodone
Reduction in progress
16.
56/55
18.56
2
-
V/S III
Sertraline, Evista,
Triamterene
Refused
17.
54/53
26.29
1
Gestational diabetes
Prevacid
Reduction in progress
18.
61/58
30.47
1
-
V/S III
Tamoxifen for 5 years,
Resveretrol, Garcinia,
Ubiquinol, Niacin, Coconut
oil, Vitamin E, Fish oil,
Reduction in progress
*V/S I – 1-2 supplements, V/S II – 3-4 supplements, V/S III – Exuberant use of nutraceuticals. 5-6 supplements or more
• 11/18 patients had a BMI greater than 25.
• 11/18 patients were taking drugs known to negatively
impact insulin resistance and increasing aromatase
(most commonly a statin drug and/or sertraline).
• 7/18 were on 5 or more supplements.
Frontal fibrosing alopecia results from an inflammatory attack on the
hair follicle in the frontal hairline in women at menopause. It occurs in
women of Northern European ancestry and appears to be increasing in
incidence [1,2].
We propose that women with FFA have difficulty navigating midlife
changes in peripheral estrogen metabolism. The up regulation in
aromatase may be physiologic and accompany age and menopause
[6]. These changes may also be magnified by medications and
supplements known to negatively affect insulin resistance and increase
aromatase [8]. Physicians caring for women with FFA should include
drug histories and drug stratification as part of their treatment plans.
The prolific use of vitamins and supplements found in this series
supports further investigation into the risks and benefits of this largely
unregulated industry.
References
[1] Ladizinski B, et al. "Frontal Fibrosing Alopecia: A Retrospective Review of 19 Patients Seen at
Duke University.” Journal of the American Academy of Dermatology. 2013; 68(5):749-755.
[2] Otani C, et al. “Frontal fibrosing alopecia associated with lichen planus pigmentosum.”
Journal of the American Academy of Dermatology. 2013; 68 (4): AB51
[3] Cutolo M, et al. "Estrogen Metabolism and Autoimmunity.” Autoimmunity Reviews. 2012;
11:A460-A464.
[4] Inoue T, et al. "The Role of Estrogen-metabolizing Enzymes and Estrogen Receptors in Human
Epidermis." Molecular and Cellular Immunology. 2011; 344: 34-40.
[5] Cutolo M, et al "Oestrogens in Rheumatic Diseases: Friend or Foe?” Rheumatology (Oxford)
2008; 47: (Suppl, 3): iii 2-5
[6] Yip L, et al. "Gene-wide Association Study between the Aromatase Gene (CYP19A1) and
Female Pattern Hair Loss." British Journal Dermatology.2009; 289-94.
[7] Marino JS, Xu Y, Hll JW. Central Insulin and leptin-mediated autonomic control of glucose
homeostasis. Trends Endocrinol Metab. 200;22:275-285.
[8] Morris P, et al. "Inflammation and Increased Aromatase Expression Occur in the Breast Tissue
of Obese Women with Breast Cancer." Cancer Prevention Research. 2011; 4(7):1021-1029.
[9] Tamir S, et al. “The Effect of Oxidative Stress on ER alpha and ER beta Expression.” Journal of
Steroid Biochemistry & Molecular Biology. 2002; 327-332.
Special thank you to Dr. John Foxworth PharmD for paper review and advice.
• 15/18 patients were Fitzpatrick level I and II, consistent
with other studies showing a predominance in women of
Northern European ancestry.
The racial predominance seen in FFA implicates a genotypic
basis for the disease. Fitzpatrick phototyping is a clinical tool
for objectively assessing skin pigmentation which may also
be a potential biomarker of vitamin D status and genotypic
variation in the human aromatase complex.
Discussion
Pt 4-Baseline and one year after changing the statin from simvistatin to atorvastatin. The
patient also started metformin which lowers aromatase