Characterizing Low-Dose Oral Minoxidil-Induced Peripheral Edema in Alopecia Patients

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Form the Division of Dermatology, Department of
Medicine, Albert Einstein College of Medicine,
Montefiore Medical Center, Bronx, New York
a
;
Albert Einstein College of Medicine, Bronx, New
York
b
; Department of Pharmacy, Montefiore
Medical Center, Bronx, New York
c
;Department
of Radiation Oncology, Montefiore Medical Cen-
ter, Montefiore Einstein Comprehensive Cancer
Center (MECCC), Albert Einstein College of Med-
icine, Bronx, New York
d
;andDepartmentof
Medical Oncology, Montefiore Medical Center,
Montefiore Einstein Comprehensive Cancer Cen-
ter, Albert Einstein College of Medicine, Bronx,
New York.
e
Funding sources: None.
Patient consent: Not applicable.
IRB approval status: IRB approval #2022-13806
from Albert Einstein College of Medicine.
Key words: cutaneous adverse event; epidermal
growth factor receptor inhibitors; non-small cell
lung cancer; oncodermatology; osimertinib; skin
of color.
Correspondence to: Beth N. McLellan, MD, Division
of Dermatology, Department of Medicine, Albert
Einstein College of Medicine, Bronx, NY
E-mail: bmclella@montefiore.org
Conflicts of interest
None disclosed.
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cancers16061079
https://doi.org/10.1016/j.jaad.2024.10.088
Characterizing low-dose oral
minoxidil-induced peripheral
edema in alopecia patients
To the Editor: Low-dose oral minoxidil (LDOM) has
emerged as an effective adjunct therapy for various
forms of alopecia. A notable adverse effect is pe-
ripheral LDOM-induced edema, reported in 2% to
3% of patients, attributed to its vasodilatory and
sodium-retaining properties.
1,2
Understanding the
specific features and risk factors associated with
Fig 1. Comparison of overall survival among racial/ethnic groups. OS, Overall survival.
ª2024 Published by Elsevier Inc. on behalf of the American Academy
of Dermatology, Inc.
JAMACAD DERMATOL
MARCH 2025
632 Brief Reports

LDOM-induced edema is crucial for optimizing pa-
tient management.
A retrospective analysis of alopecia patients treated
with LDOM (0.625-5 mg daily) at our institution
between 2023 and March 2024 with approval from
University of California, Irvine Institutional Review
Board (HS# 2016-3076). Inclusion criteria included
diagnosis of alopecia, at least 1 month of LDOM
therapy, and a minimum of 2 visits within a 12-month
period with reported peripheral swelling postmedica-
tion initiation. A total of 250 alopecia patients were
included, with a predominance of females (78%) and
a mean age of 51years (SD, 19) (Supplementary Table
I, available via Mendeley at https://data.mendeley.
com/datasets/pbv8pdv3mj/1). Among them, 22 pa-
tients (8.8%) reported edema secondary to LDOM
therapy, comprising 20 adults and 2 children. The
affected population was primarily female (90.9%; age
range 10-76 years), and predominantly comprised of
White and Asian races.
Risk factors for edema were identified using multi-
variate logistic regression models adjusted for age, sex,
race, and dose/weight (mg/kg/d) (Supplementary
Table II, available via Mendeley at https://data.
mendeley.com/datasets/pbv8pdv3mj/1). The most
common sites for LDOM-induced edema were bilat-
eral legs and feet (n¼21), face (n¼9), and hands
(n¼4). Most cases presented as pitting edema
(n¼17), typically developed within 3 months of
LDOM dosing (n¼21). Treatment strategies included
LDOM dose reduction (n¼10), discontinuation
(n¼4), or diuretic use (n¼1), resulting in complete
resolution of edema in11/22 patients, within a median
1-2 weeks. Among patients who did not adjust LDOM
regimen (n¼7), 3 had spontaneous resolution within
4 weeks, while remaining maintained LDOM dose
despite edema (n¼4) (Supplementary Table II,
available via Mendeley at https://data.mendeley.
com/datasets/pbv8pdv3mj/1). Persistent, episodic
LDOM-induced edema was observed in 8 patients,
all with predisposing factors including prior history of
peripheral edema (n¼4), cardiovascular disease
(n¼3), kidney transplant (n¼1), and prednisone
use for polymyalgia rheumatica (n¼1).
The overall incidence of LDOM edema of 8.8% in
this study exceeds rates from previous trials.
1-3
This
discrepancy may be attributed to higher initial and
incremental LDOM dosing at our center (1.25-2.5 mg
daily vs 0.25-0.625 mg daily in published studies).
1-3
The findings demonstrated a positive association be-
tween LDOM dose-weight and edema (odds ratio,
1.04; 95% CI, 1.02-1.06; P¼.001), with dose-
dependent relationship evident in the pediatric
patients.
The mechanistic underpinnings of minoxidil-
inducededema involve its direct arteriolar vasodilatory
effects, facilitation of fluid extravasation, activation of
the renin-angiotensin-aldosterone system leading to
salt and water retention, and its role as a potassium
channel opener potentially impairing lymphatic func-
tion.
4,5
These insights highlight the heightenedvulner-
ability of patients with pre-existing conditions or those
on medications affecting fluid balance to develop
edema with LDOM therapy. The prescribing informa-
tion recommends concurrent use of a diuretic to
mitigate significant fluid accumulation.
4
In summary, LDOM-induced edema represents a
dose-dependent and mostly reversible complication.
Dose adjustment or discontinuation typically improves
edema within weeks, though it may persist intermit-
tently in some patients, especially those with pre-
existing risk factors. We underscore the importance of
cautious, incremental dosing of LDOM, especially in
patients with a history of peripheral edema.
Jesse Salas, BS, Ilhan Esse, BA, Colin M. Kincaid,
BS, Abhinav Birda, BA, Sarah Choe, BS, and
NatashaA.Mesinkovska,MD,PhD
From the Department of Dermatology, University of
California, Irvine, Irvine, California.
Author Esse contributed equally to this work.
Funding sources: None.
Patient consent: Not applicable.
IRB approval status: Reviewed and approved by UCI
IRB HS# 2016-3076.
Key words: alopecia; alopecia areata; androgenetic
alopecia; edema; low-dose oral minoxidil.
Correspondence to: Natasha A. Mesinkovska, MD,
PhD, Department of Dermatology, University of
California, Irvine, 843 Health Sciences Rd, Hewitt
Hall 1001, Irvine, CA 92697
E-mail: natashadermatology@gmail.com
Conflicts of interest
None disclosed.
REFERENCES
1. Randolph M, Tosti A. Oral minoxidil treatment for hair loss: a
review of efficacy and safety. J Am Acad Dermatol. 2021;84:
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2. Jimenez-Cauhe J, Saceda-Corralo D, Rodrigues-Barata R, et al.
Safety of low-dose oral minoxidil treatment for hair loss. A
systematic review and pooled-analysis of individual patient
data. Dermatol Ther. 2020;33:e14106.
3. Va~
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an S, Pirmez R, Hermosa-Gelbard A, et al. Safety of
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1404 patients. J Am Acad Dermatol. 2021;84:1644-1651.
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Brief Reports 633

4. Sanabria B, Vanzela T de N, Miot HA, M€
uller Ramos P. Adverse
effects of low-dose oral minoxidil for androgenetic alopecia in
435 patients. J Am Acad Dermatol. 2021;84:1175-1178.
5. Garner BR, Stolarz AJ, Stuckey D, et al. K ATP channel openers
inhibit lymphatic contractions and lymph flow as a possible
mechanism of peripheral edema. J Pharmacol Exp Ther. 2021;
376:40-50.
https://doi.org/10.1016/j.jaad.2024.09.078
Retrospective cohort study of novel
oral agents lenalidomide and
duvelisib for relapsed or refractory
mycosis fungoides and S
ezary
syndrome
To the Editor: Treatment options for cutaneous T-cell
lymphomas including mycosis fungoides (MF) and
S
ezary syndrome (SS) are limited especially in the
relapsed and refractory setting. The novel oral agents
duvelisib, a PI3K inhibitor, and lenalidomide, an
immunomodulator, have shown some efficacy in
cutaneous T-cell lymphomas, however real-world
data are limited.
1,2
We retrospectively analyzed 16
patients with MF/SS consecutively treated at the
University of Pennsylvania with either lenalidomide
or duvelisib as monotherapy or a part of a multiagent
regimen. The primary outcome was overall survival
(OS); secondary outcomes included progression-free
survival (PFS), treatment response, and development
of treatment-related adverse events (TRAEs). Survival
was analyzed using the Kaplan-Meier method and log
rank analysis; associations of clinical variables with
outcomes were assessed using Cox proportional
Table I. Cohort demographics and treatment information
Characteristic
Lenalidomide cohort
N= 6 (%)
Duvelisib cohort
N=10(%) Pvalue
Age ( y) 74.3 (61.9-85.6) 63.9 (62.1-72.1) .7482
Sex (male) 4 (66.7%) 6 (60%) .7897
Race (White) 4 (66.7%) 6 (60%) .1255
Diagnosis
MF 4 (66.6%) 9 (90%) .247
SS 2 (33.3%) 1 (10%)
History of LCT 3 (50%) 4 (40%) .6957
Elevated LDH 5 (83.33%) 8 (80%) .5482
Prior treatment
History of HDACi 5 (83.3%) 9 (90%) .6966
History of mogamulizumab 3 (50%) 3 (30%) .4237
Median prior systemic therapies 7 (5-11) 5.5 (4-10) .0042*
Concurrent radiation 3 (50%) 3 (30%) .4237
Initial dose in mg
y
10 1 (16.7%) N/A
15 0 (0%) 1 (10%)
20 1 (16.7%) N/A
25 4 (66.6%) 4 (40%)
75 N/A 5 (50%)
CD41disease 5 (83.3%) 9 (90%) .6966
Stage
IB-IIB 4 (66.66%) 3 (30%) .0222*
IIIA-IIIB 2 (33.33%) 1 (10%)
IVA-IVB 1 (16.7%) 6 (60%)
ECOG PS 0-1 5 (83.3%) 7 (70%) .1035
Combination with romidepsin 0 (0%) 3 (30%) .1366
Disease flare 2 (33.3%) 2 (20%) .5507
TRAE any grade 4 (66.7%) 6 (60%) .7884
For continuous values, median is shown with interquartile range in parentheses. Chi-square test Pvalues and t-test used when appropriate.
ECOG PS, Eastern Cooperative Oncology Group Performance Status; HDACi, histone deacetylase inhibitor; LCT, large cell transformation; LDH,
lactate dehydrogenase; MF, mycosis fungoides; N/A, not applicable; SS,S

ezary syndrome; TRAE, treatment-related adverse event.
*Significant with P\.05 cutoff.
y
Lenalidomide was given daily for 21 days out of a 28-day cycle. Duvelisib was given twice daily continuously; patients initially treated with
duvelisib 50 mg or 75 mg twice daily were dose reduced after 8 weeks to 25 mg twice daily or lower.
ª2024 by the American Academy of Dermatology, Inc.
JAMACAD DERMATOL
MARCH 2025
634 Brief Reports