Exogenous Ochronosis with Use

of Low Potency Hydroquinone in

A Caucasian Patient
DIPRESENTASIKAN OLEH: FATHIA K. DINANTI (30101407183)
Case Report Identity
Writer:
◦Luke Maxfield and David A. Gaston
◦Lake Erie College of Osteopathic Medicine, USA
Institution:
◦Dermatology & Laser Center, Medical Center Clinic, USA
◦Florida State University College of Medicine, USA
Year : 2015
Introduction
Exogenous ochronosis  maculopapular paradoxical
hyperpigmentation terlihat setelah pemakaian zat pemutih kulit yang
mengandung hidrokuinon.
Pada kebanyakan kasus, terjadi pada kulit dengan tipe yang lebih
gelap dan menggunakan hidrokuinon potensi tinggi jangka panjang.
Case Report
A 53 year old Caucasian lady presented complaining of an
asymptomatic eruption of tiny grey-black maculopapules around her
eyes.
This condition had been present and gradually worsening for about a
year.
She denied any skin lesions like this elsewhere, but had noted an
orange-brown discoloration of her fingernails the past six months.
She had been using a non-prescription 3% hydroquinone cream to
lighten "dark circles" under her eyes for about eighteen months.
A punch biopsy was taken of the periorbital speckles.
Pathology showed the dermis to have scattered yellow-orange-brown (so
called "ochre colored") particles, some with a banana shape and many with an
angulated, fractured glass appearance.
Discussion
Ochronosis is a rare condition resulting from
deposition of homogentisic acid into the dermis of
the skin.
Two types of ochronosis
◦exogenous ochronosis  mostly because of HQ using.
◦endogenous ochronosis or alkaptonuria.
Endogenous Ochronosis
Rare autosomal recessive metabolic disorder because deficiency of
homogentisic acid oxidase.
Homogentisic acid is broken down by the enzyme homogentisic acid oxidase and
a hydroquinone metabolite of tyrosine. With decreased enzyme activity, the
excess homogentisic acid irreversibly binds to dermal fibrillar collagen, which
results in skin pigmentation, cartilage deposition, and darkening of the urine
after prolonged exposure to air.
Diagnosis of alkaptonuria is suspected by clinical history and characteristic urine
changes, with the gold standard of diagnosis being confirmation of homogentisic
acid in the urine
Exogenous Ochronosis
Exogenous ochronosis is most commonly seen after use of skin lightening
agents containing hydroquinone, but a similar-appearing condition has also
been reported after contact with resorcinol, phenol, mercury, picric acid, and
use of antimalarials.
Incidence of exogenous ochronosis is directly related to both dose and duration
of use, although occurrence with 2% topical hydroquinone treatment has
provided emphasis of duration more than dosage.
Advanced Examination
By dermoscopy  lesions appear as dark brown globules and
globular a diffuse brown background.
By RCM (Reflectance Confocal Microscopy) dark, well-defined,
round-to-oval and dermal banana shaped structures, the latter
finding being more specific as it had not been attributed to any
previous cutaneous structure or disease.
Diagnosis can be confirmed by skin biopsy, yielding characteristic
yellow-brown, banana-shaped fibers within the papillary dermal
layer with or without sarcoidal granulomas or multinucleated giant
cells.
Teori : Produksi Melanin
Melanin diproduksi oleh melanosit, yang berasal dari lengkung
saraf dan selama proses perkembangan embriogenik bermigrasi dan
menetap di lapisan basal epidermis.
Melanosit memiliki organel yang disebut melanosom sebagai
organel pembentuk pigmen melanin.
Ligmen melanin akan dilepaskan oleh dendrit melanosit ke
keratinosit yang ada di sekitarnya untuk kemudian memberikan
warna pada kulit.
Pada individu dengan warna kulit cerah, ukuran melanosom lebih
kecil dan berada di antara keratinosit dalam satu kelompok.
Sedangkan, pada individu yang berkulit lebih gelap, melanosom lebih
besar, berwarna gelap, dan tersebar secara individual.
Bertambahnya melanin di kulit menyebabkan satu keadaan yang
disebut hiperpigmentasi / hipermelanosis.
 Hydroquinon
Hidrokuinon topical bekerja dengan
memblokir enzyme tyrosinase yang
berperan dalam produksi melanin.
Pada pemakaian konsentrasi tinggi
(4%)  iritasi , eritema, dan rasa
terbakar.
Pada pemakaian konsentrasi rendah
(2%) jangka waktu lama 
leukoderma kontak dan okronosis
eksogen.
Teori 1
Hidrokuinon berkompetisi
dengan tirosin sebagai
substrat untuk tirosinase
sehingga tirosinase
mengoksidase hidokuinon
dan menghasilkan
benzokuinon yang toksik
terhadap melanosit. (1)
Teori 2
Hidrokuinon menghambat
aktivitas enzim asam
homogentisat oksidase 
akumulasi asam homogentisat 
berpolimerasi membentuk
pigmen onkronotik  deposit
pada dermis. (2)
Beberapa teori pathogenesis EO
Banana-shaped collagen fibers covered by
ochronotic pigment.
Therapy
The first step is to remove the inciting agent. While trichloroacetic
acid and cryotherapy are ineffective, other medical treatments
report varied success.
Retinoic acid has shown to improve discoloration for some patients;
however, it has also been reported to cause hyperpigmentation in
others.
High SPF sunscreen in combination with retinoic acid or low
potency corticosteroids has also shown some success, and oral
tetracycline reportedly successfully treated one patient.
Further treatment involves a series of
superficial, ablative modalities in hopes
of removing the pigment deposition
without causing scarring.
Methods include chemical peels, CO2
laser, cryotherapy, dermabrasion, and
fractional carbon dioxide and erbium-
YAG lasers
Sekian, Terimakasih