Letters to the Editor
In conclusion, there may be variations in the clinical presen-
tation, laboratory findings and response to treatment of AE.
Therefore, we suggest that the diagnosis should be confirmed
with the mutation analysis of the SLC39A4 gene.
CONFLICT OF INTEREST: None declared.
Hilal KAYA ERDOGAN,1 Isil BULUR,1
Zeynep Nurhan SARACOGLU,1 Huseyin ASLAN,2
Sultan Durmus AYDOGDU,3 Bahadir YILDIZ1
Departments of 1Dermatology, 2Genetics, and 3Pediatrics, Faculty of
Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
doi: 10.1111/1346-8138.13313
Efficacy and safety of minoxidil 3% lotion for beard
enhancement: A randomized, double-masked,
placebo-controlled study
Dear Editor,
The beard is hairs grown on the chin and jaw line. Beard
enhancement is a desirable feature for some men to improve
masculine and attractive appearance, signaling dominance,
strength and self-confidence. The physician, professor, engi-
neer, artist and pastor represent occupational stereotypes in
which male members are expected to have a beard.1 Some
women also find men wearing beard more attractive. Further-
more, in the hair restoration technique called follicular unit
extraction, beard hairs are used as donor units on recipient
areas of androgenetic alopecia patient whose scalp donor
hairs are insufficient.2 Topical minoxidil has been prescribed
for the treatment of androgenetic alopecia. To our knowledge,
there is no published study about minoxidil for beard enhance-
ment. The present study aimed to compare the efficacy and
safety of minoxidil 3% with placebo in beard hair stimulation.
The 16-week randomized, double-masked, placebo-con-
trolled was approved by Mae Fah Luang University (Clini-
calTrial.gov ID: NCT02275832). Forty-eight men, aged 20
60 years, who desired beard enhancement were enrolled in the
Table 1. Mean change from baseline in hair diameter and count at week 16
Mean change from baseline (mean  SE)
3% minoxidil Placebo
Hair diameter (lm) 0.43  2.31 (P = 0.852) 0.57  1.23 (P = 0.650)
Hair count 5.00  0.72 (P < 0.001) 0.35  0.31 (P = 0.277)
Paired Students t-test. Independent sample t-test. SE, standard error.
Correspondence: Chuchai Tanglertsampan, M.D., Mae Fah Luang University (Bangkok), 38/11-13 Asoke Place Building, Asoke Road (Sukhumvit
21), Klongtoey Nua, Wattana, Bangkok 10110, Thailand. Emails: drchuchait@yahoo.com, chuchai.tan@mfu.ac.th
968
REFERENCES
1 Zhou XY, Chen XJ, Wang S et al. One recurrent homozygous muta-
tion of SLC39A4 in a girl with acrodermatitis enteropathica from
southwestern China. Int J Dermatol. 2016; 55: 223225.
2 Kury S, Kharfi M, Kamoun R et al. Mutation spectrum of human
SLC39A4 in a panel of patients with acrodermatitis enteropathica.
Hum Mutat 2003; 22: 337338.
3 Kilic M, Taskesen M, Coskun T et al. A zinc sulphate-resistant acro-
dermatitis enteropathica patient with a novel mutation in SLC39A4
gene. JIMD Rep 2012; 2: 2528.
4 Kilic SS, Giraud M, Schmitt S et al. A novel mutation of the SLC39A4
gene causing acrodermatitis enteropathica. Br J Dermatol 2007; 157:
386387.
5 Garza-Rodrguez V, de la Fuente-Garca A, Liy-Wong C et al. Acro-
dermatitis enteropathica: A novel SLC39A4 gene mutation in a
patient with normal zinc levels. Pediatr Dermatol 2015; 32: 124125.
study. Exclusion criteria included hair disorders or using medi-
cations for hair regrowth within the previous 6 months. Patients
were instructed to apply 0.5 mL of topical assigned solution on
the chin and jaw line twice daily. Patients beard photographs
were taken for global photographic score as a primary efficacy
assessment every 4 weeks. Three doctors evaluated pho-
tographs on a 7-point scale (+3 to 3).3 The changes in hair
counts and diameter from baseline were measured as sec-
ondary efficacy assessment. The measurement landmark was
3-cm lower from the vermilion border of the lower lip at mid-
line. Patients self-assessments were surveyed on the 16th
week using a 7-point scale the same as the global photo-
graphic score. Side-effects were evaluated by detailed history
and physical examination.
Forty-six of 48 patients completed the study. At week 16,
the global photographic score in the minoxidil group was sig-
nificantly higher than that in the placebo group using the
MannWhitney U-test (P = 0.002). Table 1 demonstrates that
mean change in hair count from baseline significantly increased
in the minoxidil group compared with the placebo group. No
Difference between two groups (mean  SE)
0.13  2.62 (P = 0.961)
4.65  0.78 (P < 0.001)
2016 Japanese Dermatological Association

statistically significant difference was found between minoxidil
and placebo groups for mean change in hair diameter. For
patients self-assessments, the minoxidil group was signifi-
cantly superior to the placebo group using the MannWhitney
U-test (P = 0.013). The adverse reactions were mild and not
statistically significantly different between groups.
Topical minoxidil has been used to treat androgenetic
alopecia. We also demonstrated that it could be used for eye-
brow hypotrichosis.4 In this trial, minoxidil lotion was superior
to placebo for beard enhancement based on the global photo-
graphic scores, mean change from baseline in hair count and
patients self-assessments. There was no statistically signifi-
cant difference between groups for changes in hair diameter
from baseline. This can be explained by: (i) the increase in hair
count, especially non-terminal hairs; and (ii) measurement of
hair was done on both terminal and non-terminal hairs. The
exact mechanism of minoxidil in promoting hair growth is still
unclear but there are many hypotheses.5 In conclusion, minoxi-
dil 3% lotion is effective and safe for beard enhancement.
CONFLICT OF INTEREST: None declared.
Toxic epidermal necrolysis with isolated neutropenia related
to the use of levetiracetam
Dear Editor,
Levetiracetam (LEV) is a second-generation anticonvulsant that
belongs to the category of non-aromatic antiepileptic drugs
(AED) and does not form an arene oxide. It has been consid-
ered relatively safe compared with other aromatic AED. Toxic
epidermal necrolysis (TEN) induced by LEV is extremely rare
and, to date, only four cases of TEN or StevensJohnson syn-
drome with LEV have been reported worldwide.1,2
A 36-year-old man consulted our department for generalized
erythematous patches and bullae with a mild fever (up to
37.8C). Due to a traffic accident, the patient had undergone
neurosurgical intervention and received LEV treatment at a
dose of 1.0 g daily for 1 month before the visit. Skin lesions
initially developed 4 weeks after starting LEV as generalized
erythematous targetoid patch involving 40% of the body sur-
face area (BSA). He was diagnosed with an erythema multi-
forme type drug eruption. A third-generation cephalosporin
(ceftriaxone) and non-steroidal anti-inflammatory drugs
(NSAIDs) (ketorolac) were stopped, excluding antihypertensive
agents, hepatotonics and LEV which were known to have
fewer side-effects. Systemic and topical steroids were initiated.
However, over the next 3 days, the skin lesions rapidly pro-
gressed to numerous vesiculobullae over 70% of the BSA
(Fig. 1ac). A skin biopsy of flaccid bullae on the abdomen
Correspondence: Joo Yeon Ko, M.D., Ph.D., Department of Dermatology, College of Medicine, Hanyang University, 222-1, Wangsimni-ro,
Sungdong-gu, Seoul 133-792, Korea. Email: drko0303@hanyang.ac.kr
2016 Japanese Dermatological Association
Letters to the Editor
Sittichai INGPRASERT, Chuchai
TANGLERTSAMPAN, Nalintip
TANGPHIANPHAN, Chinnawat REANMANEE
Department of Dermatology, School of Anti-aging and Regenerative Medicine,
Mae Fah Luang University Hospital (Bangkok), Bangkok, Thailand
doi: 10.1111/1346-8138.13312
REFERENCES
1 Hellstrom A, Tekle J. Person perception through facial photographs:
effects of glasses, hair, and beard on judgments of occupation and
personal qualities. Eur J Soc Psychol 1994; 24(6): 693705.
2 Umar S. Use of body hair and beard hair in hair restoration. Facial
Plast Surg Clin North Am 2013; 21(3): 469477.
3 Olsen EA, Whiting D, Bergfeld W et al. A multicenter, randomized,
placebo-controlled, double-blind clinical trial of a novel formulation of
5% minoxidil topical foam versus placebo in the treatment of andro-
genetic alopecia in men. J Am Acad Dermatol 2007; 57(5): 767774.
4 Lee S, Tanglertsampan C, Tanchotikul M, Worapunpong N. Minoxidil
2% lotion for eyebrow enhancement: a randomized, double-blind,
placebo-controlled, split-face comparative study. J Dermatol 2014;
41: 149152.
5 Trueb RM, Lee WS. Male Alopecia. Springer: Cham, 2014.
showed detachment of the epidermis with extensive cell necro-
sis and mild lymphocytic infiltration in the upper dermis
(Fig. 1gi). Laboratory and radiological examinations to rule out
the infection including blood culture, skin culture, urine culture,
chest computed tomography (CT) and abdominal CT were
negative. Finally, the patient was diagnosed with TEN probably
caused by LEV. The LEV was stopped and a higher dose of
systemic steroid was administrated including daily 625 mg of
methylprednisolone followed by a 60 mg prednisolone per day
with conservative management. The occurrence of new skin
lesions stopped and showed gradual improvement 3 days after
the cessation of LEV. Otherwise, his leukocyte count showed
2.7 9 109/L with the blister development and exacerbated to
1.7 9 109/L with an absolute neutrophil count of 0.88 9 103/
mm3 (normal range, 1.578.30 9 103/mm3) after 5 days. After
14 days of the discontinuation of LEV, the re-epithelialization
was completed with post-inflammatory hyperpigmentation
(Fig. 1df) and the absolute neutrophil count returned to nor-
mal. During a 10-month follow up, no relapse was observed
even though he took NSAIDs (ketolorac) and third-generation
cephalosporin (cefcapene) prescribed in otolaryngology. Based
on these findings, the diagnosis of LEV-induced TEN was
made and the Naranjo score was calculated to be 8, suggest-
ing that LEV is a probable cause for this condition.3
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