212 Research Letters J AM ACAD DERMATOL

JANUARY 2018

Table I. Risk of vitiligo in organ transplant recipients compared to matched controls

Univariate analysis Multivariate analysis
Population Vitiligo 3-year risk of vitiligo Crude OR (95% CI) P value Adjusted OR (95% CI)* P value
Matched controls 44,136 88 0.20% Reference Reference
Organ transplant 14,712 8 0.05% 0.272 (0.132-0.562) .0004 0.305 (0.148-0.630) .0013
recipients

CI, Confidence interval; OR, odds ratio.

*Adjusted by age, sex, and insurance type.

Table II. Risk of vitiligo in organ transplant recipients according to the transplanted organ and the use of
immunosuppressants
Immunosuppressant*
3-year risk Mycophenolate Mycophenolate
Population Vitiligo of vitiligo Tacrolimus mofetil Cyclosporine sodium Azathioprine Sirolimus
Matched controls 44,136 88 0.20%
Organ transplant 14,712 8 0.05% 60.36% 53.81% 42.44% 28.02% 5.93% 2.89%
recipients
Kidney 10,223 6 0.06% 50.08% 53.14% 53.49% 38.90% 8.10% 4.05%
Liver 4474 2 0.04% 85.19% 54.49% 15.62% 3.31% 0.67% 0.25%
Heart and/or 214 0 0.00% 49.53% 77.10% 62.15% 19.16% 10.28% 0.93%
lung

*Immunosuppressants taken for [180 days in organ transplant recipients.

3. Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK.
Presence of T cells and macrophages in inflammatory vitiligo
skin parallels melanocyte disappearance. Am J Pathol. 1996;
148:1219-1228.
4. Gupta AK, Ellis CN, Nickoloff BJ, et al. Oral cyclosporine in the
treatment of inflammatory and noninflammatory dermatoses.
A clinical and immunopathologic analysis. Arch Dermatol.
1990;126:339-350.
5. Radmanesh M, Saedi K. The efficacy of combined PUVA and
low-dose azathioprine for early and enhanced repigmentation
in vitiligo patients. J Dermatolog Treat. 2006;17:151-153.
http://dx.doi.org/10.1016/j.jaad.2017.08.015
Activation of melanocytes in
idiopathic guttate hypomelanosis
after 5-fluorouracil infusion using
a tattoo machine: Preliminary
analysis of a randomized, split-body,
single blinded, placebo controlled
clinical trial
To the Editor: This letter presents a preliminary
analysis of the first 8 patients who have completed
a randomized clinical trial for idiopathic guttate
hypomelanosis (IGH) treatment that was approved
by the respective ethics committee and registered in
the ClinicalTrials.gov database under identifier
NCT02904564. The rationale for this study was the
preliminary histologic analysis of IGH spots in which
we observed varying degrees of papillary dermis
fibrosis.1 Fulton et al2 described the repigmentation
of hypopigmented scars arising from different
etiologies after mechanical removal of dermal
fibrosis. The formulated hypothesis was that IGH
repigmentation could occur if the underlying dermal
fibrosis were removed. Instead of mechanically
removing this fibrosis, as described by Fulton et al,2
we attempted to remove or reduce it by delivering
medication with antifibrotic properties. Because of
its low cost, injectable 5-fluorouracil (5-FU) was the
drug of choice, which has been used for scar
treatment since 1990.3 We named the drug
delivery technique used in this clinical trial MMP
(the Portuguese acronym for microinfus~ao de
medicamentos na pele [ie, microinfusion of drugs
into the skin]).4 This technique drew inspiration from
the ancient art of tattooing. In MMP, the
tattoo machine’s needles convey the medication
contained in the sterile needle cartridge into the
skin (Fig 1, B and C )—ie, the microneedling and
injection processes occur simultaneously (Fig 1, A).
Needling depth is gradually adjusted until mild
pinpoint bleeding is achieved (Fig 1, D), which is
an indication that the dermis has been reached.
The intervention was done using a Cheyenne
tattoo machine by MT.DERM (Berlin, Germany), the
only equipment of the sort approved by the Brazilian
Health Agency (ANVISA) for medical use. Two
dermatologists, blinded to the randomization, deter-
mined the limb present the best therapeutic outcome
by clinical analysis (Fig 2, A-D). Statistical analysis
was performed using Antera 3D5 (Miravex, Dublin,
J AM ACAD DERMATOL Research Letters 213
VOLUME 78, NUMBER 1

Fig 1. Details of the microinfus~ao de medicamentos na pele (MMP; microinfusion of drugs into
the skin) procedure. A, Sequence of illustrations detailing how the drug is inserted into the
dermis. The device used for MMP contains a set of needles in a sterile cartridge. The physician
loads the cartridge with the desired drug and starts the microneedling process. During each
microneedling cycle, the needles are soaked with the drug, and the skin is then perforated
deeply enough to reach the dermis, with simultaneous delivery of the drug. B, Close view of the
cartridge itself. The arrow indicates the level of 5-fluorouracil, also visible because of the
bubbles. The circle indicates the tips of the set of needles. C, Enlarged image of the set of
needles. D, Appearance of 2 idiopathic guttate hypomelanosis lesions partially subjected to
drug delivery. The procedure was initially performed only in the central regions of these lesions
and was subsequently used to treat the entirety of these spots.

Ireland; Fig 2, E and F ), a device with image analytics
software capable of quantifying melanin in each IGH
macule (Fig 2, G). Fig 2, H presents the repigmenta-
tion percentages of both limbs for all patients. The
data show that IGH repigmentation after 5-FU MMP
treatment was statistically higher when compared
with placebo MMP (75.3% 5-FU repigmentation vs.
33.8% placebo, P \.001). Two patients submitted to
biopsy 40 days after the procedure presented
numerous melanocytes in the 5-FUetreated areas,
thereby eliminating the possibility of postinflamma-
tory hyperpigmentation. One patient with
Fitzpatrick skin phototype III developed hyperpig-
mentation areas on both treated limbs 30 days after
the intervention, which spontaneously reversed
within 2 months.
Partial repigmentation of placebo-treated lesions
may have been caused by collagen remodeling
induced by simple microneedling of the papillary
dermis. We believe that 5-FU MMP treatment may be
beneficial in treating IGH. Even though no adverse
effects were observed in MMP-treated patients, the
safety and efficacy of this 5-FU drug delivery method
needs to be proven by means of additional studies.
Tattooing is an ancient technique under public domain
done mainly by tattoo artists, we have chosen to copyright
the acronym MMP in Brazil and the United States and
grant free use exclusively to dermatologists who are
members of the Brazilian Society of Dermatology and
equivalent entities around the world. Dr Arbache’s com-
mercial involvement in this investigation was required in
order to obtain approval of the equipment for medical use
214 Research Letters J AM ACAD DERMATOL
JANUARY 2018

Fig 2. Idiopathic guttate hypomelanosis (IGH) treatment results. A and B, The right leg of
patient number 8 before and 150 days after treatment with placebo (PL; saline). C and D, The
left leg of patient number 8 before and 150 days after treatment with 5-fluorouracil (5-FU). The
arrow in part C indicates the IGH lesion analyzed by the Antera 3D system in parts E and F.
E and F, Antera 3D photos before treatment and 150 days after the intervention. The white
arrow indicates the IGH lesion for which melanin will be quantified. G, Graph generated using
Antera 3D software. The light blue and red columns quantify melanin before and 150 days after
the intervention, respectively. H, Percentage analysis of repigmentation in each patient’s limbs
with 5-FU treatment (red columns) compared with placebo (blue columns). I, Placebo-treated
IGH. A few randomly distributed melanocytes can be seen. J, 5-FUetreated IGH displaying
numerous melanocytes. The melanin contained in the melanocytes has not yet been transferred
to the keratinocytes. (I and J, Melan A stain; original magnification, 3200.)

under Brazilian health legislation (as enforced by Ag^ encia
Nacional de Vigil^ancia Sanitaria) and to render this
investigation acceptable for the relevant ethics committee.
We hereby inform that the clinical results described and
documented herein can be achieved using any available
tattoo machine. Dr Arbache is a member of a staff that
trains Brazilian dermatologists in the use of this technique.
Samir Arbache, MD,a Dirlene Roth, MD,a Denise
Steiner, MD, PhD,a Juliano Breunig, MD, PhD,b
Nilceo Schwery Michalany, MD,c Samia Trigo
Arbache, MD,d Luciana Gasques de Souza, MD,e
and Sergio Henrique Hirata, MD, PhDf
Department of Dermatology, University of Mogi das
Cruzes (Universidade de Mogi das Cruzes -
UMC)/SP, Brazila; Department of Medicine,
University of Santa Cruz do Sul (Universidade
de Santa Cruz do Sul e UNISC)/RS, Brazilb;
Department of Pathology, S~ ao Paulo State School
of Medicine, Federal University of S~ ao Paulo
(Universidade Federal de S~ ao Paulo e UNI-
FESP)/SP, Brazilc; Clinics Hospital, S~ ao Paulo
University (Universidade de S~ ao Paulo e USP)/
SP, Brazild; private practice, S~
ao Paulo, Brazile;
Department of Dermatology, S~ ao Paulo State
School of Medicine, Federal University of S~ ao
Paulo (Universidade Federal de S~ ao Paulo e
UNIFESP)/SP, Brazilf
The machine, its cartridges, and the medicines
used in this study were supplied by Traderm
(S~
ao Jose dos Campos, Brazil).
J AM ACAD DERMATOL
VOLUME 78, NUMBER 1
Correspondence to: Samir Arbache, MD, Depart-
ment of Dermatology, University of Mogi das
Cruzes/SP, Rua Coronel Madeira 45, Centro, S~
ao
Jose dos Campos, S~
ao Paulo 12245-760, Brazil
E-mail: samir@dermocentro.com.br
REFERENCES
1. Falabella R, Escobar C, Giraldo N, et al. On the pathogenesis of
idiopathic guttate hypomelanosis. J Am Acad Dermatol. 1987;
16:35-44.
2. Fulton JEJ, Rahimi AD, Mansoor S, et al. The treatment of
hypopigmentation after skin resurfacing. Dermatol Surg. 2004;
30:95-101.
3. Fitzpatrick RE. Treatment of inflamed hypertrofic scars using
5-FU. Dermatol Surg. 1999;25:224-232.
4. Arbache S, Godoy CE. Microinfusion of drugs into the skin with
tattoo equipment. Surg Cosmet Dermatol. 2013;5:70-74.
5. Matias AR, Ferreira M, Costa P, Neto P. Skin colour, skin
redness and melanin biometric measurements: comparison
study between AnteraÒ 3D, MexameterÒ and ColorimeterÒ.
Skin Res Technol. 2015;21:346-362.
http://dx.doi.org/10.1016/j.jaad.2017.08.019
Hidradenitis suppurativa burden
of disease tool: Pilot testing of a disease-
specific quality of life questionnaire
To the Editor: Hidradenitis suppurativa (HS) is a
chronic inflammatory condition affecting intertrigi-
nous areas of the body that dramatically impairs
quality of life (QoL) and has a substantial psychoso-
cial burden.1,2 Full remission of HS is rare, making
improvements in QoL a critical goal of therapy.
Currently, when investigating the impact of HS, we
are limited to generic QoL questionnaires, none of
which are specific for HS. We propose a disease-
specific tool that would better capture the unique
burden of disease caused by HS, which is necessary
to determine the impact of therapeutic interventions
in clinical trials and in the clinical setting.
We used both consensus expert opinion from 8
medical dermatologists and patient input to develop
the Hidradenitis Suppurativa Burden of Disease
(HSBOD) tool (Supplemental Material; available at
http://www.jaad.org). The HSBOD is a 19-item self-
administered visual analog scale (VAS) questionnaire
designed to provide a more nuanced and accurate
understanding of the overall burden of disease
among patients with HS. Questions in this novel
tool include a 10-cm VAS ranging from 0 (no
complaints) to 10 (worst complaints). VASs have
been validated, making survey completion rapid
and easy while yielding more precise responses;
however, the HSBOD requires abstract thinking,
which may be difficult for some patients.3,4 We
compared HSBOD tool performance to the
Research Letters 215
commonly used, nonedisease-specific Dermatology
Life Quality Index (DLQI). HSBOD questions were
divided into 5 domains: ‘‘symptoms and feelings,’’
(questions 1-9 and 17) and impact upon ‘‘daily
activities,’’ (questions 10 and 13) ‘‘leisure,’’ (questions
11, 13, and 14) ‘‘work/school,’’ (questions 12, 18, and
19), and ‘‘personal relationships’’ (questions 6-9, 15,
and 16). Twenty-nine patients (none of whom
participated in tool development) with HS who
were diagnosed by a Board-certified dermatologist
completed both surveys without assistance.
The reliability, or the degree to which the HSBOD
produces stable results, was assessed by Cronbach
alpha.5 Cronbach alpha of 0.936 for this study
indicates good internal consistency within the
HSBOD. The median HSBOD score was 5.5 of 10
and the median DLQI was 13 of 30. Spearman rho
was calculated as a measure of the strength of the
rank correlation between HSBOD and DLQI.
Individuals’ HSBOD scores were plotted against
corresponding DLQI scores for the overall summary
score and subscales (Fig 1). Questions on the
HSBOD corresponding to ‘‘symptoms and feelings’’
( ¼ 0.681, P \.001), ‘‘leisure’’ ( ¼ 0.661, P \.001),
and ‘‘daily activities’’ ( ¼ 0.598, P \ .001) had a
strong correlation to the corresponding DLQI sub-
scales. HSBOD questions corresponding to ‘‘per-
sonal relationships’’ ( ¼ 0.419, P ¼ .024) and ‘‘work/
school’’ ( ¼ 0.310, P ¼ .101) had a moderate
correlation with the corresponding DLQI questions,
although the ‘‘work/school’’ domain did not achieve
statistical significance. The lack of a strong correla-
tion between the HSBOD and DLQI for ‘‘personal
relationships’’ and ‘‘work/school’’ may reflect that
the HSBOD has several questions designed to
specifically investigate issues in HS, while the DLQI
has fewer generic questions for all skin disorders. We
feel this lack of correlation could represent
shortcomings of the DLQI in fully capturing the
many facets of HS contributing to the burden of
disease.
Although our study is limited by the small sample
size and likely increased disease severity among
patients in a tertiary care referral center, the HSBOD
questionnaire shows internal reliability and corre-
lates strongly ( ¼ 0.604, P \ .001) with a validated
nonspecific skin QoL tool (the DLQI). Future studies
with broader data collection should confirm item
selection, validity, and reliability of HSBOD consid-
ering the lower item-scale correlations for a subset of
the 19 items.
We thank the patients who have graciously accepted to
complete the surveys. Without their participation, this
study would not have been possible.