Hydroquinone cream is the standard depigmentation or skin lightening agent. Clinically it is used to treat areas of dyschromia, such as in:
Its most common use is in patients with post-inflammatory hyperpigmentation and melasma.
Postinflammatory hyperpigmentation results from cutaneous inflammation, causing increased melanin production. Common causes of postinflammatory hyperpigmentation are acne vulgaris, eczematous dermatoses, contact dermatitis, psoriasis, lichen planus, and burns. The most common cause of hyperpigmentation results from photodamage from sunlight exposure. Inflammation increases the release and oxidation of arachidonic acid to prostaglandins and leukotrienes resulting in increased melanin production. Hydroquinone is used to treat postinflammatory hyperpigmentation along with photoprotection. Improvement with hydroquinone occurs over several weeks to months.
Melasma is an acquired hyperpigmentation and presents on sun-exposed areas of the face, commonly the forehead, cheeks, and chin. It presents as symmetrically distributed pigmented macules and patches. Factors that play a role in the pathogenesis of melasma are darker skin, UV radiation, hormones, genetics, and antiepileptic medications. Exposure to UV radiation is the main factor in pathogenesis as UV radiation increases the levels of alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone, which increases the proliferation of melanocytes. Also, at the dermal layer, increased expression of stem cells of fibroblasts and tyrosine kinase receptor c-kit is resent in melasma lesions. Also noted in lesions are upregulation of vascular endothelial growth factor (VEGF), Wnt, and reactive oxygen species seen after UV induced dermal inflammation. Vascularization and melanocyte hyperreactivity results from this UV induced inflammation leading to increased melanin production and hyperpigmentation. Patients who are pregnant or use oral contraceptives are also at risk because the expression of estrogen receptors seems to rise in melasma lesions as well. Estrogen also induces the release of melanocyte-stimulating hormone (MSH), which stimulates tyrosinase leading to increased production of melanin. For this reason, melasma occurs more frequently in females vs. males . Treatment is similar to postinflammatory hyperpigmentation, with photoprotection and hydroquinone being the first line.
Photoprotection is a significant key in maximal benefit from hydroquinone use. Melanocytes are stimulated from UVB, UVA, and even visible light leading to pigmentation. Therefore, broad-spectrum sunscreens are recommended.
Hydroquinone is not FDA approved due to its unknown safety profile. It is banned in the EU, Australia, and Japan.
Hydroquinone acts as a skin depigmentation agent by inhibiting melanin synthesis. It inhibits the conversion of L-3,4- dihydroxyphenylalanine (L-DOPA) to melanin by inhibiting tyrosinase due to its structural similarity to an analog of melanin precursors.
The pathway of melanin synthesis:
Hydroquinone is only used topically as a depigmentation agent. A thin layer is applied with fingertips and rubbed into the face (or other affected areas) 1 to 2 times a day for 3 to 6 months. If there are no results after 2 to 3 months, hydroquinone should be discontinued. It is important to evenly apply hydroquinone over the entire face to prevent uneven pigmentation and use concurrently with sunscreen to protect from damaging UV light, which increases pigmentation. Physicians recommended stopping treatment after this time for a few months before restarting to decrease the risk of side effects. It can also be applied during weekends only or three times a week for more extended maintenance therapy with minimal complications.
Hydroquinone is available in 2% over the counter or as 4% prescribed. It comes in the following dose forms: cream, emulsion, gel, or solution.
Multiple studies have shown that maximum results occur when using hydroquinone as combination therapy with a retinoid and corticosteroid. The most widely used triple combination cream is composed of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%. Use in combination with other agents requires a prescription by a dermatologist.
Results vary among each patient.
About 35% to 45% of hydroquinone is absorbed systemically after topical use.
Studies also suggest that hydroquinone can falsely elevate capillary glucose when measured with a glucometer.
Concerns that hydroquinone cream is carcinogenic have not been confirmed in clinical practice or human research.
Pregnancy Category C
About 35 to 45% of the topical hydroquinone dose is absorbed systemically. Current studies have not shown an increased risk of malformations or adverse effects in pregnant women, but it is recommended to minimize exposure due to the substantial absorption. The safety of breastfeeding mothers and in children is yet to be established and as such should be avoided.
Monitor for any hypersensitivity or long term irritation, in which case the medication should be discontinued. Also, in the rare case ochronosis develops, stop using hydroquinone and consult a physician.
No significant toxicity has been found with the topical use of the hydroquinone cream.
Some studies report malignancies in animals treated for an extended period with large oral doses.
Hydroquinone in the environment
In the environment, hydroquinone is a chemical and can be toxic in the setting of human and industrial activities by promoting the generation of reactive oxygen species, oxidative stress and hence the potential for DNA damage. It is a major benzene metabolite and is known to be hepatotoxic and carcinogenic in these settings. Some studies suggest it can promote tumor cell growth and suppress the immune response. It is used in photography and is present in dyes, paints, varnishes oils, and motor fuels. In its oxidized form, it is more toxic and less degradable. It demonstrates high toxicity to aquatic organisms, and rodents and may induce leukemia, renal tubular cell tumor, and liver cancer. It has also been found to influence immune cell responses and causes an increase in an allergic response by increasing interleukin-4 production and immunoglobulin E levels.
The health care team, such as physicians, nurses, and pharmacists play an important role in monitoring patients on hydroquinone. It is important to monitor patients to ensure that they only use the medication as prescribed for no more than 5 to 6 months to limit side effects. Also, it is important to follow instructions for the medication application, its frequency, keep a watchful eye for any adverse effect, which should be clearly explained to the patient. Patients should be instructed to cease using the medication if any sort of irritation, hypersensitivity, or allergic reaction occurs. The rare, yet most potentially harmful, side effect of ochronosis needs to be explained to patients using hydroquinone, and they should be instructed to discontinue this medication immediately if this occurs.
We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.
This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.
|Epstein JH, Postinflammatory hyperpigmentation. Clinics in dermatology. 1989 Apr-Jun; [PubMed]|
|Stephens TJ,Babcock M,Bucay V,Gotz V, Split-face Evaluation of a Multi-ingredient Brightening Foam Versus a Reference Control in Women with Photodamaged Facial Skin. The Journal of clinical and aesthetic dermatology. 2018 Oct; [PubMed]|
|Tomita Y,Maeda K,Tagami H, Mechanisms for hyperpigmentation in postinflammatory pigmentation, urticaria pigmentosa and sunburn. Dermatologica. 1989; [PubMed]|
|Katsambas AD,Stratigos AJ, Depigmenting and bleaching agents: coping with hyperpigmentation. Clinics in dermatology. 2001 Jul-Aug; [PubMed]|
|Sofen B,Prado G,Emer J, Melasma and Post Inflammatory Hyperpigmentation: Management Update and Expert Opinion. Skin therapy letter. 2016 Jan; [PubMed]|
|Kauh YC,Zachian TF, Melasma. Advances in experimental medicine and biology. 1999; [PubMed]|
|Mahmoud BH,Ruvolo E,Hexsel CL,Liu Y,Owen MR,Kollias N,Lim HW,Hamzavi IH, Impact of long-wavelength UVA and visible light on melanocompetent skin. The Journal of investigative dermatology. 2010 Aug; [PubMed]|
|Lieberman R,Moy L, Estrogen receptor expression in melasma: results from facial skin of affected patients. Journal of drugs in dermatology : JDD. 2008 May; [PubMed]|
|Speeckaert R,Van Gele M,Speeckaert MM,Lambert J,van Geel N, The biology of hyperpigmentation syndromes. Pigment cell [PubMed]|
|Bozzo P,Chua-Gocheco A,Einarson A, Safety of skin care products during pregnancy. Canadian family physician Medecin de famille canadien. 2011 Jun; [PubMed]|
|Rendon MI,Barkovic S, Clinical Evaluation of a 4% Hydroquinone 1% Retinol Treatment Regimen for Improving Melasma and Photodamage in Fitzpatrick Skin Types III-VI. Journal of drugs in dermatology : JDD. 2016 Nov 1; [PubMed]|
|Choukem SP,Efie DT,Djiogue S,Kaze FF,Mboue-Djieka Y,Boudjeko T,Dongo E,Gautier JF,Kengne AP, Effects of hydroquinone-containing creams on capillary glycemia before and after serial hand washings in Africans. PloS one. 2018; [PubMed]|
|Enguita FJ,Leitão AL, Hydroquinone: environmental pollution, toxicity, and microbial answers. BioMed research international. 2013; [PubMed]|
The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pharmacy-Pharmacotherapy. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.
StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pharmacy-Pharmacotherapy, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pharmacy-Pharmacotherapy, you will already be prepared.
Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pharmacy-Pharmacotherapy. When it is time for the Pharmacy-Pharmacotherapy board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pharmacy-Pharmacotherapy.