Treatment of Exogenous Ochronosis With a Q

COMMUNICATIONS AND BRIEF REPORTS
Treatment of Exogenous Ochronosis With a Q-Switched
Alexandrite (755 nm) Laser
S UPRIYA G. B ELLEW, MD, n
AND
T INA S. A LSTER , MD w
New Jersey Medical School, Newark, New Jersey, and wWashington Institute of Dermatologic Laser Surgery,
Washington, DC
n
BACKGROUND. Exogenous ochronosis is a cutaneous disorder
characterized by blue-black or slate-gray hyperpigmentation
resulting from the prolonged use of certain topical agents, most
commonly hydroquinones. It is notoriously difficult to treat.
OBJECTIVE. To report the effectiveness of a quality-switched
(QS) 755-nm alexandrite laser in treating hydroquinoneinduced exogenous ochronosis.
METHODS. Hydroquinone-induced exogenous ochronosis in
two patients was treated with a QS alexandrite laser. The first
patient received six treatments (average fluence 5 7.8 J/cm2) at
2-month intervals. The second patient received four treatments
(average fluence 5 6.9 J/cm2) at 4-month intervals. Biopsies of
lesional skin were obtained before and after laser treatment for
histologic evaluation.
RESULTS. Significant lightening of the pigmented skin areas was
achieved in both patients without scarring or textural changes.
Decreased dermal pigmentation was observed on histologic
examination of treated skin specimens.
CONCLUSION. The QS alexandrite laser can effectively treat
exogenous ochronosis without untoward side effects.
S. G. BELLEW, MD, AND T. S. ALSTER, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL
SUPPORTERS.
OCHRONOSIS IS classified as either endogenous or
exogenous in origin. Endogenous ochronosis, also
known as alkaptonuria, is a rare, autosomal recessive
multisystem disorder resulting from a lack of homogentisic acid oxidase, the enzyme necessary for conversion of homogentisic acid to acetoacetic and fumaric
acids. Affected individuals develop widespread homogentisic acid deposition in numerous tissues, including
skeletal cartilage, cardiac valves, and skin.1
In contrast, exogenous ochronosis is confined to the
skin and presents clinically with asymptomatic blueblack or slate-gray cutaneous pigmentation typically
affecting the malar eminences, temples, inferior
cheeks, neck, back, and the extensor surfaces of the
extremities.2,3 Exogenous ochronosis consists of three
stages: initial erythema and mild pigmentary change,
followed by hyperpigmentation, black colloid milia,
and atrophy, and finally papulonodules.4
Exogenous ochronosis most commonly results from
the use of topical hydroquinones but has also been
associated with phenol, quinine injection, resorcinol,
and oral antimalarials.5,6 It has been reported almost
exclusively in South African blacks, where its prevalence is estimated at 28% to 35% of the population.7 Initially, only the use of a high concentration of
hydroquinone for a prolonged period of time was
Address correspondence and reprint requests to: Tina S. Alster, MD,
Washington Institute of Dermatologic Laser Surgery, 2311 M Street,
NW Suite 200, Washington, DC, 20037.
thought to result in exogenous ochronosis, but recent
reports have shown the development of the disorder
with topical application of 2% hydroquinone for as
little as 3 months.8
Histologically, ochronosis is characterized by yellow-brown, banana-shaped pigment fibers in the
dermis in its early stages. With progression to the
papulonodular stage, the ochronotic fibers degenerate,
forming a colloid milium. Some lesions also demonstrate the formation of sarcoid-like granulomas
surrounding the ochronotic fibers. In severe cases,
transepidermal elimination of pigment and pseudoepitheliomatous hyperplasia have also been described.9
Exogenous ochronosis has been largely refractory to
topical agents, including tretinoin, cryotherapy, trichloroacetic acid, sunscreens, and corticosteroids.
Clinical improvement has been reported after treatment with oral tetracycline, dermabrasion, and CO2
laser irradiation; however, results have not been uniform, and the condition remains difficult to treat.9–11
We report the first cases of hydroquinone-induced
exogenous ochronosis successfully treated with a Qswitched (QS) 755-nm alexandrite laser.
Case Reports
Case 1
A 47-year-old African American female presented with
an 8-year history of blue-black facial discoloration.
r 2004 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing, Inc.
ISSN: 1076-0512/04/$15.00/0 Dermatol Surg 2004;30:555–558
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BELLEW AND ALSTER: LASER TREATMENT FOR OCHRONOSIS
She admitted to the heavy use of bleaching creams for
‘‘sun spots’’ on her face over a period of several months
before the development of the offending pigmentary
changes. Previous treatment with topical tretinoin,
corticosteroids, chemical peels, and microdermabrasion had been ineffective. Physical examination revealed diffuse, dark-brown patches on the cheeks and
numerous, grouped, pinpoint slate-gray colored macules on the forehead, infraorbital regions, nose, and
cheeks (Figure 1). Systemic workup for endogenous
ochronosis was negative. Skin biopsy findings demonstrating pathognomonic yellow-brown dermal deposits confirmed the diagnosis of ochronosis (Figure 2).
The patient was treated with a QS 755-nm
alexandrite laser (Tatulazr; Candela Laser Corp.,
Wayland, WA). Topical 30% lidocaine in Velvachol
cream was used to achieve cutaneous anesthesia.
Lesional areas were treated at a fluence of 7.0 J/cm2
using nonoverlapping 3-mm collimated spots. An
immediate ash-white tissue response was observed in
treated areas. The ochronotic skin was treated at
bimonthly time intervals with an end treatment fluence
of 8.0 J/cm2 (average fluence 5 7.8 J/cm2). Progressive
lesional fading was noted after each of six treatments
(Figure 3). The patient was encouraged to avoid sun
exposure and to apply a zinc oxide-containing
sunscreen to facial skin throughout the course of treatment. Posttreatment histologic evaluation of skin revealed no residual pigmented deposits in the dermis or
evidence of fibrosis or epithelial disruption (Figure 4).
Case 2
A 46-year-old Native American male presented with a
7-year history of brownish black hyperpigmented
patches on his cheeks that developed within 1 year
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Figure 2. Yellow-brown pigment deposits are evident in the dermis
pretreatment (hematoxylin and eosin, 40 magnification).
of using a hydroquinone-containing bleach to lighten
his complexion. He reported worsening of the lesions
after they first appeared, despite cessation of the
bleaching cream. Physical examination revealed slategray, hyperpigmented patches over the temples and
malar regions bilaterally. Skin biopsy confirmed the
diagnosis of ochronosis. Systemic workup for endogenous causes was negative.
The same protocol as described in case 1 was
implemented with an initial fluence of 6.0 J/cm2. The
patient received a total of four treatments at 4-month
intervals with a maximum fluence of 7.0 J/cm2
(average fluence 5 6.9 J/cm2). Treatment intervals were
prolonged in order to allow time for postinflammatory
hyperpigmentation to resolve in this patient with
persistent sun exposure. Marked lightening of the
ochronotic skin lesions was achieved at the end of
treatment. No textural change or other untoward
effects were observed.
Discussion
Figure 1. Slate-gray patches on the nose, malar eminence, and
nasolabial fold consistent with exogenous ochronosis.
The source of ochronotic pigment fibers is a subject of
debate. Some believe they represent abnormal elastic
fibers, whereas others argue that collagen fibers
produce the ochronotic pigment.8,12 Penneys13 suggested that hydroquinone may cause local inhibition of
homogentisic acid oxidase, leading to the local
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BELLEW AND ALSTER: LASER TREATMENT FOR OCHRONOSIS
557
Figure 3. Significant lesional lightening achieved after six QS alexandrite
(755-nm) laser treatments.
accumulation of homogentisic acid, which subsequently
polymerizes to form pigment. Findlay et al.14 hypothesized that the hydroquinone passes into the dermis after
its effect on melanocytes has ceased and that it or its
metabolites are subsequently engulfed by fibroblasts
that excrete the pigmented material. The etiologic role
of melanocytes in the pathogenesis of exogenous
ochronosis is supported by the case of a black patient
with vitiligo who applied a hydroquinone-containing
cream to the face. Ochronotic hyperpigmentation
resulted on areas of normal skin, whereas the vitiliginous areas remained unaffected.15 In addition, sunlight
is also thought to play a role, perhaps through
activation of melanocytes, given the preferential involvement of sun-exposed areas in exogenous ochronosis.16
The successful use of a QS alexandrite laser for the
treatment of tattoos and dermal pigmented lesions has
been well documented.17–20 Its efficacy in treating
tattoos results from the delivery of high energies in
ultra short pulses, with subsequent shattering of tattoo
ink particles. The fragmented pigment particles are
then phagocytosed and removed through lymphatic
drainage or transepidermal elimination.21 Analogous
to tattoos that result from exogenous pigment
implanted in the dermis, exogenous ochronosis also
results from dermal pigment deposition. The QS
alexandrite laser’s efficacy in treating ochronosis may
therefore result from disruption of the dermal ochronotic pigment fibers, allowing for their subsequent
removal. It is expected that other pigment-specific
lasers, such as the QS 694-nm ruby and QS 1064-nm
Nd:YAG, would yield similar clinical results in these
patients. The use of either a 755-nm alexandrite laser
or 1064 nm Nd:YAG laser would be preferable to a
694-nm ruby laser because their longer wavelengths
result in less absorption by epidermal melanin and
Figure 4. No ochronotic pigment, fibrosis, or epidermal disruption is
seen in lesional skin at 2 months after six QS 755-nm alexandrite laser
treatments (hematoxylin and eosin, 40 magnification).
deeper tissue penetration. This is an especially
important consideration in patients with exogenous
ochronosis, the vast majority of whom have dark skin
tones and are thus at greatest risk for permanent
hypopigmentation or scarring when epidermal disruption occurs. For this reason, it may be prudent to
perform a ‘‘test’’ area with any of these systems before
pursuing full treatment.
The relative ease with which these patients were
treated and the long-term positive clinical outcomes
that were achieved signify the importance of pigmentspecific laser treatment for exogenous ochronosis.
Prior treatments obtained by these patients were
costly, in terms of both monetary expense and time
expended, and yielded inadequate cosmetic benefit.
Although continued sun protection is necessary in
order to optimize clinical efficacy of laser treatment, it
remains unclear whether the use of adjuvant topical
therapies (e.g., tretinoin, corticosteroids) is beneficial.
Conclusion
Exogenous ochronosis is a cosmetically disfiguring
disorder with historically disappointing therapeutic
options. Treatment with a QS alexandrite laser can
effectively and safely improve the dyspigmentation
associated with exogenous ochronosis.
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BELLEW AND ALSTER: LASER TREATMENT FOR OCHRONOSIS
Acknowledgment The authors kindly acknowledge the assistance of Dr. Glenn Genest and Dr. Bernard Gasch.
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