Postinflammatory Hyperpigmentation | BareFacedTruth.com

Postinflammatory Hyperpigmentation

The word inflammation comes from the Latin “inflammo”, meaning “I set alight, I ignite”. Inflammation is part of the body’s immune response. Initially, it is beneficial when, for example, your skin experiences damage from trauma, chemicals, or irradiation. Inflammation begins the process of repair, and so is key to survival of all tissues. However, inflammation can sometimes cause further inflammation, in a  self-perpetuating cycle.  Complications then ensue.

This is BFT’s final installment in our series on cutaneous dyschromias – abnormalities of skin pigmentation. Our first post covered lentigines (singular = lentigo), those pesky and dreaded tan and brown “age spots” that occur on sun exposed surfaces. Our second topic discussed melasma, a commonly seen sex hormone-related hyperpigmentation that affects ten times as many women as men. Today we look at postinflammatory hyperpigmentation, perhaps the worst of the lot because of its potential to cause the most severe and challenging to treat cosmetic consequences. Three words of caution common to all dyschromias, and to all ethnic and racial groups, no matter whether fair or dark skinned:   SUNBLOCK.   SUNBLOCK.   SUNBLOCK.

DISCLAIMER: As always, BFT writes to generally educate, inspire, and entertain. For specific advice or treatment concerning your own skin, see your personal physician.

Postinflammatory hyperpigmentation(“PIH”) is an acquired condition in which excessive melanin deposition occurs at sites of skin inflammation or injury. Although it can be seen in all skin types, it more frequently affects darker Fitzpatrick skin types (IV, V, and VI.) Examples include African Americans, Hispanics/Latinos, Asians, Native Americans, Pacific Islanders, and those of Middle Eastern descent.  Within each given group, the incidence is higher among darker skin individuals, suggesting that the degree of pigmentation rather than race/ethnicity per se may be more contributory to PIH development. PIH often has significant psychosocial impact.

Etiology

PIH in Pseudofolliculitis barbae

Acne-induced PIH – Fitzpatrick skin type V

 

 

 

 

 

 

Many types of inflammatory dermatoses or cutaneous injuries can cause changes in pigmentation. Some in particular, however, show a proclivity to develop PIH rather than hypopigmentation. Examples are fungal and viral infections (chicken pox, measles, etc.), allergic reactions to insect bites or contact dermatitis, psoriasis or lichen planus. PIH may also result from hypersensitivity reactions to medications, cutaneous injury from irritants, burns, or cosmetic procedures. Highly common causes of PIH are acne vulgaris, atopic dermatitis, and impetigo. Among African Americans with pseudofolliculitis barbae (“razor bumps”), the prevalence of PIH is estimated between 45 and 83 percent.

PIH post dermatitis

 

 

 

 

 

 

 

Pathogenesis

melanophagic activity in the dermis

PIH results from overproduction of melanin or irregular dispersion of pigment and typically manifests in a pattern of distribution identical to the initial inflammatory process. Melanocyte activity has been

shown to be stimulated by prostanoids, cytokines, chemokines, and other inflammatory mediators as well as reactive oxygen species released during the inflammatory process. The location of the excess pigment within the layers of the skin determine its coloration. When confined to the epidermis, production and transfer of melanin to keratinocytes is increased. Epidermal hypermelanosis will appear tan, brown, or dark brown and may take months to years to resolve without treatment. PIH within the dermis results from inflammation-induced damage to basal keratinocytes, which release large amounts of melanin. The free pigment is then phagocytosed by macrophages, now called melanophages, in the upper dermis.  Hyperpigmentation within the dermis has a blue-gray appearance and may either be permanent or resolve over a protracted period of time if left untreated. PIH can worsen with ultraviolet (UV) irradiation or with persistent or recurrent inflammation.

Exogenous ochronosis

Treatment

The management of PIH begins with addressing the underlying inflammatory condition. Initiating treatment early for PIH may help hasten its resolution and prevent further darkening. It is, however, important to be mindful of the potential the treatment itself has to cause or exacerbate PIH by causing irritation.

Photoprotection is integral to treatment and prevention of PIH. Daily use of broad spectrum sunscreen (SPF of 30) and sun-protective measures, such as avoidance and protective clothing, are mainstays of therapy. This is particularly true for those with higher Fitzpatrick skin types who may not typically normally wear sunscreen or realize the darkening effects UV irradiation has on hyperpigmentation.

Aside from photoprotections (always the first line of defense), there are a variety of medications and procedures that can safely and effectively treat PIH in darker skinned patients. Topical depigmenting agents, such as hydroquinone, azelaic acid, kojic acid, licorice extract, and retinoids, can be effective alone or in combination with other agents, and procedures such as chemical exfoliation and laser therapy can also be incorporated into the management strategy if needed. Topical agents are of use in treating epidermal PIH. Deeper dermal pigmentation does not respond well.

Medical therapy

Hydroquinone (HQ), a phenolic compound that blocks the conversion of dihydroxyphenylalanine (DOPA) to melanin by inhibiting tyrosinase, remains the mainstay of treatment for PIH. A recognized complication of HQ is paradoxical hyopigmentation, especially around the area of treatment. HQ is commonly used at concentrations from 2 to 4% but can be prescribed in strengths up to 10% and is available over the counter (OTC) at 2% in the United States. More recently, HQ has been formulated with other agents, such as retinoids, antioxidants, glycolic acid, sunscreens, and corticosteroids, to increase efficacy. Irritant reactions can result from long-term daily use of 4% or higher HQ, particularly when used in combination with other agents that can be irritating, such as retinoids. However, concomitant use of a topical corticosteroid can reduce irritation, thereby decreasing the risk of further hyperpigmentation.

Interestingly, a small number of patients exposed to chronic higher doses of hydroquinone may develop a difficult to treat paradoxical hyperpigmentation of the dermis termed exogenous ochronosis. It occurs most commonly in persons who have used higher-dosed preparations of hydroquinone, often unregulated formulations sold in ethnic markets.

In 2006, the United States Food and Drug Administration (FDA) released a statement proposing a ban on all OTC HQ agents based on rodent studies, which suggested that oral HQ may be a carcinogen. However, there have been no reports of skin cancers or internal malignancies associated with topical HQ use. To date, a final ruling by the FDA is still pending.

            Mequinolis a derivative and alternative to hydroquinone. Although the two agents are related, mequinol is thought to be less irritating to the skin than HQ. The drug is available by prescription in a

2% concentration and is typically formulated with 0.01% tretinoin, a retinoic acid and penetration enhancer. The mechanism by which mequinol causes depigmentation may involve a competitive inhibition of tyrosinase. Several clinical studies have shown that mequinol effectively treats solar lentigines in all patients including ethnic populations

            Retinoids are structural and functional analogues of vitamin A, and are effective alone or in combination with other agents for the treatment of PIH in ethnic patients. Retinoids exert multiple biological effects that result in skin lightening including the modulation of cell proliferation, differentiation, and cohesiveness; induction of apoptosis; and expression of anti-inflammatory properties.

Third-generation retinoids, adapalene and tazarotene, are synthetic topical agents that are also effective in the treatment of PIH. Adapalene is formulated in creams or gels in 0.1 to 0.3% concentrations; whereas, formulations of tazarotene include 0.05 and 0.1% creams or gels. Both agents have been shown in clinical studies to safely and effectively treat PIH, particularly acne-induced PIH, in darker skinned individuals.

            Azelaic acid is a naturally occurring dicarboxylic acid isolated from the organism responsible for Pityriasis versicolor that has been shown to be effective in the treatment of PIH. Azeleic acid has several mechanisms by which it depigments the skin including tyrosinase inhibition as well as selective cytotoxic and antiproliferative effects toward abnormal melanocytes through the inhibition of DNA synthesis and mitochondrial enzymes.

            Kojic acid is a fungal metabolite of certain species of AcetobacterAspergillus, and Penicillium. Its depigmenting ability originates from a potent inhibition of tyrosinase by chelating copper at the active site of the enzyme.

            Arbutinis extracted from the dried leaves of the bearberry shrub or pear, cranberry, or blueberry plants. Arbutin is another derivative of HQ, but without the melanotoxic effects. Arbutin causes depigmentation by inhibiting not only tyrosinase activity but also melanosome maturation. Although its efficacy is dose-dependent, higher concentrations of arbutin can lead to a paradoxical hyperpigmentation. Synthetic forms of arbutin, alpha-arbutin and deoxyarbutin, exhibit greater ability to reversibly block melnagenesis.

Niacinamide is the physiologically active derivative of vitamin B3 or niacin. In-vitrostudies show that niacinamide significantly decreases melanosome transfer to keratinocytes without inhibiting tyrosinase activity or cell proliferation, and niacinamide may also interfere with the cell-signaling pathway between keratinocytes and melanocytes to decrease melanogenesis.

            N-acetyl glucosamine (NAG) is an amino sugar that is a precursor to hyaluronic acid and is found throughout nature and human tissues. Its depigmenting ability originates from the inhibition of tyrosinase glycosylation, a step necessary in the production of melanin.

  Ascorbic acid or vitamin C is a naturally occurring antioxidant obtained from certain fruits and vegetables. It causes skin lightening by interacting with copper ions at the tyrosinase active site and by reducing oxidized dopaquinone, a substrate in the melanin synthetic pathway. In addition to skin lightening, other advantages of AA include not only antioxidant effects but some studies also demonstrate anti-inflammatory and photoprotective properties.

            Licorice root extract (Glycyrrhiza glabraGlycyrrhiza uralensis) is a common ingredient found in many skin-lightening cosmeceuticals, and is also used in the treatment of a wide variety of diseases even outside the scope of dermatology due to its anti-inflammatory, antiviral, antimicrobial, and anticarcinogenic properties. Some of the active ingredients in licorice root extract include glabridin, which inhibits tyrosinase and possesses anti-inflammatory effects, and liquiritin, which does not inhibit tyrosinase but causes depigmentation by melanin dispersion and removal.

            Soy. The activation of protease-activated receptor 2 (PAR-2) cell receptors found on keratinocytes mediates the transfer of melanosomes from melanocytes to surrounding keratinocytes. Soy proteins, such as soybean trypsin inhibitor (STI) and Bowman-Birk inhibitor (BBI), inhibit the activation of these cell receptors, and as a result, phagocytosis of melanosomes into keratinocytes is reduced leading to reversible depigmentation.

Destructive therapies

Destructive therapies are based on the principle that damage or trauma to the skin’s surface results in a healing or restorative response.  In theory, and usually in practice, this can result in a diminution of hyperpigmentation. The problem is that they also typically cause another round of inflammation.  Individuals who are prone to a hyperpigmentary response to inflammation in the first place could see a return, or even a worsening, of ther condition they are trying to treat.

 

Before and After Chemical Peel for PIH

           Chemical peels. In 2008, chemical peeling was the fourth most common nonsurgical cosmetic procedure performed in the United States, and dyschromias, such as PIH, are one of the most common indications for this procedure in skin of color.

For darker skinned individuals, superficial chemical peels, which penetrate into the papillary dermis, are generally well tolerated with good clinical results. However, care should be taken in selecting and using the specific chemical peel to avoid irritation, which can worsen PIH and lead to other complications, such as new areas of dyspigmentation, keloid formation, and hypertrophic scarring.

A detailed history, including other dermatological conditions, current oral and topical medications, history of herpes simplex virus (HSV) infection, past reactions to other cosmetic procedures, and a skin examination should be obtained prior to the procedure.

          Glycolic acid (GA), found in sugarcane, is a naturally occurring alpha-hydroxy acid (AHA) that induces epidermolysis, disperses basal layer melanin, and increases dermal collagen synthesis.

           Salicylic acid (SA), derived from willow tree bark, is a beta-hydroxy acid that induces keratolysis by disrupting intercellular lipid linkages between epithelioid cells.

Other complications include hypopigmentation, hypertrophic scarring, and keloid formation. Patients should also be educated on the importance of photoprotection to prevent or avoid worsening PIH after chemical peeling.

          Laser and light-based therapies. Although topical skin-lightening agents remain the treatment of choice for PIH, lasers and light sources may be an effective adjunct to therapy or alternative for treatment failures. Typically, energy from short wavelength lasers is more efficiently absorbed by epidermal melanin while longer wavelengths penetrate deeper with more selective absorption by dermal targets making them safer to use for darker-skinned patients. There have been case reports of the successful treatment of PIH with blue light photodynamic therapy, neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, and fractional photothermolysis in darker skin types

Before and After Laser Treatment for PIH

Cosmetic camouflage may be useful to conceal pigmentary disorders, vascular lesions, scars, and chronic skin conditions that are not amenable to medical or surgical treatments. These coverage techniques can help alleviate the patient’s distress regarding their appearance and significantly improve quality of life.

Camouflage can be particularly useful in darker skinned individuals where pigmentary changes may be more noticeable and when highly visible parts of the body are affected by the disease, such as the face, neck, and hands.  Cosmetic covers can be applied for subtle coverage up to full concealment.

 

Topical Application of Anti-inflammatory (stem cell derived) Cytokines

Melanocyte responses to trauma and inflammation are incompletely understood and highly complex. Hence, melanocytes can respond with normal, increased, or decreased production of melanin.

In PIH, production is increased. It is thought that both hyperpigmentation and hypopigmentation result from cytokines and inflammatory mediators from keratinocytes, melanocytes, and inflammatory cells that are released in an inflammatory process in the skin. These include leukotriene (LT), prostaglandins (PG), and thromboxane (TXB).

PGE1 and PGE2 increase melanogenesis strongly while PGA1 and PGD2 represent strong inhibitors Leukotrienes such as LTC4 and LTD4, are metabolites of the lipoxygenase pathway and are able to induce the proliferation of melanocytes in vitro. Histamine, another inflammatory agent, may activate melanogenesis via proteinase A activation.

DrJohn has written extensively on cytokine patterns elsewhere on BFT, explaining that bone marrow derived mesenchymal stem cultures produce predominantly anti-inflammatory patterns of cytokines. BFT is aware of at least one PIH subject who has experienced substantial improvement in her appearance following eight weeks of twice daily application of a product containing such a pattern of anti-inflammatory cytokines. The photos she provided to speak for themselves.

before stem cytokines (AnteAge)

after stem cytokines (AnteAge)

 

 

68 Comments

  1. Curious says:

    Thanks for posting this. I am dealing with this now for the first time in my life because of a really bad skincare product experience earlier this year. I am still trying to stay away from products that have EGF in them out of balance, but they are in so many things! Sunscreens even! I am also considering trying the AnteAge product in the future as it looks really good. I have a question what is the scientific opinion on stem cell activators in products vs cell culture mediums or cytokines?

    I was also looking at this product – http://www.stemcello.com/shop/page.html?id=15

    I know better than to use the EGF serum, but I was wondering about the Emortal serum and cream. Is there such a thing as a stem cell activator?

    Thanks in advance. 🙂

    • drjohn says:

      Curious: we are really glad that you are. This is an example of bad science and/or deceptive marketing taken to the extreme. We need to do a whole post in this.

      Stem cell activators? of course there are many. But the real question is “activated how, and to do what?” There are plenty of ways of perturbing stem cells, or any cells, in a lab culture. Cells have defensive responses to harmful things. That’s how cells can survive, and help our organs and whole bodies to survive. if you activate then by adding toxic substances stem cells product large quantities of inflammatory cytokines and growth factors. A mixture of these inflammatory signals would harm skin, and cause it to age faster if applied daily.

      Here is where the StemCello folks come across as complete scientific fools. They actually document (admit) that this is exactly what they have “discovered”. A stem cell activator that causes substantial increases in TGF-B1, VEGF and IL-6 to pour out of these cells. This is a cytokine profile associated with inflammatory emergencies. TGF-B1 is the growth factor associated with the inflammation of acne vulgaris, many forms of dermatitis, skin sclerosis, and fibrotic healing. IL-6 is associated with inflammation during heart attacks, the induction of many cancers including breast cancer. Advanced/metastatic cancer patients have higher levels of IL-6 in their blood, correlating with poor survival rates. IL-6 stimulates the inflammatory and auto-immune processes in many diseases such as diabetes, atherosclerosis, depression,Alzheimer’s Disease,systemic lupus erythematosus, multiple myeloma, prostate cancer, Behçet’s disease, and rheumatoid arthritis.

      When you see stem cells “activated” by a toxin to produce such inflammatory signals, it is like a cry for help to other stem cells (bone marrow) and other cells from the immune system. A genuine 911 emergency.

      If these so called scientists knew anything about the biochemistry of cells they would recognize that their product (assuming it does anything in live humans) would be inflammatory as all get out.

      In my lectures I often point out that you can get these same results in the lab by merely spitting into the culture flask. There are lots of substances in saliva that will “stimulate stem cells” in culture. For best results, use rat saliva, which has 1,000 times as much of these irritants as human spit.

      Perhaps one of these days soon some misinformed company like this one will put rat spit in a bottle and sell it as a stem cell activator.

  2. Curious says:

    Thank you so much Dr. John!

    I really appreciate your detailed answer. I definitely didn’t understand the science behind the product, but I had no idea that this could cause such an inflammatory response in my skin. I will definitely pass on this product.

    The advertising really sucked me in though. This idea of making your skin constantly rejuvenate itself sounded really appealing!

  3. Stan says:

    Thanks for a thorough and informative article on hyperpigmentation!

    I am currently suffering from hyperpigmentation for the first time, and it took a while before I realised that was what it was.

    I had fillers in my under eye tear throughs, but had them removed due to discolouration and bad placement. Both after filler injections and filler removal I used tanning beds, unaware of the risk of hyperpigmentation.

    Now, 2 months after the removal of the fillers I still suffer from hyperpigmentation along tear through, with so sign of improvement.

    I don’t know if you answer questions in this comment section, but I am really wondering whether hyperpigmentation is permanent, meaning I have to wear sunscreen in this area for the rest of my life (I’ve never worn sunscreen before), or if it resolves completely, to the point where it doesn’t bother me anymore.

    I don’t know if it’s dermal or epidermal, but I really hope it’s epidermal. The skin under the eyes is really thin, so I don’t know if you can use chemical peel in this area?

    • drjohn says:

      Hi Stan, hyperpigmentation after removal of fillers is a common problem. And the thin skin around the eye is particularly susceptible. Yes, you should use sunscreen and avoid tanning beds (even if you hadn’t suffered the damage). Peels are inflammatory, and carry their own risk of PIH. PIH takes time to resolve and the trick is to set up an anti-inflammatory environment using products that reduce chemical stress (antioxidants), and promote regeneration and an anti-inflammatory environment. This allows resident macrophages to remove pigment trapped in cells, with a gradual restoration.

  4. Rosanne Serra says:

    Dr. John,
    I suffered PIH after Intensed Pulse Light( IPL) treatment to my abdomen and upper back to remove brown spots .I now have multiple dark brown squares( the shape of the laser) on those areas. It has been 6 months and nothing has improved after one course of hydroquinone and one course of triluma ( combination of hydroquinone, retin A and hydrocortisone). I have also not exposed those areas to the sun. Do you have any experience with this type of PIH? Do I continue to try different treatments or is it permanent?
    Thank You
    Rosanne

    • drgeorge says:

      Hi, Rosanne. So sorry to hear of your pigmentation issue following what you had hoped would help resolve a different kind of pigment issue i.e. brown spots. IPL is an interesting modality in that it can result in significant improvement for some conditions in some people, and do the exact opposite for others. PIH (post inflammatory hyperpigmentation) is a particularly troublesome issue for darker skinned people (Fitzpatrick types 4, 5, 6) but can cause problems in just about anyone. Inflammation following any kind of trauma (including thermal) causes excessive melanin production in people prone to PIH, and if severe enough can actually cause the death of melanocytes leading to spots with little or no pigment. Topical bleaching agents with or without retinoid can be helpful in lightening dark patches. Most instances self resolve in 3-6 months but can be permanent.

      Tooting our own horn a little, we and affiliated practitioners using our anti-inflammatory stem cell skincare products, are not seeing PIH. In fact, we recommend people planning on facial aesthetic medical procedures pre-treat for a week or two in order to reduce inflammation before treatment and then use product immediately thereafter for the entire duration of the healing process to continue anti-inflammatory effects. Let us know how you do.

      http://www.dr-kimmig.de/global/download/Poster_ASLMS.pdf

  5. Anja Schmidt says:

    Dear Dr. John,

    I have postinflammatory hyperpigmentation due to chemical peels. Unfortunately it is oocated in the dermis. What can I do best to resolve the pigmentation. It is all over my face. I have tried chemical peels (GA) and topical agents like IKLEN (b-resorcinol) and azelaic acid. Now having startet on a test spot 2 percent HQ (Klingmann formula). What about this Anteage stemcell products? Could they help me? Thank you so much in advance for your kind help.

    • drgeorge says:

      Anja, we are empathetic to your plight. PIH is a common problem for many, especially those with higher Fitzpatrick skin types (III to VI), in whom even minor trauma can cascade into dark persistent marks. Avoiding sun exposure is a no-brainer, that should always be practiced. Our bias, as our readers know, is application of skincare products that have pronounced anti-inflammatory effects. We are strong believers that pre-treatment for a week or two with our products can settle the skin down and help reduce inflammatory sequelae. We have not conducted controlled studies but the clinical response in our own patients and countless others seems to support that conclusion. But your question has implications that warrant a lengthy answer for our readership.

      For starters, you draw a clear distinction between deeper hyperpigmentation (dermal) and more superficial (epidermal.) As you will read below, the prognosis and options for treatment are different. First and foremost, darker skin types must strongly consider the greater chance that they will have undesirable PIH sequelae from any type of aesthetic treatment. The information below is an abridge version of material on Medscape.com.

      Postinflammatory hyperpigmentation (PIH) is a frequently encountered problem and represents the sequelae of various cutaneous disorders as well as therapeutic interventions. This acquired excess of pigment can be attributed to various preceding disease processes that affect the skin such as infections, allergic reactions, mechanical injuries, reactions to medications, phototoxic eruptions, trauma (eg, burns), and inflammatory diseases including lichen planus, lupus erythematosus, and atopic dermatitis.

      PIH can also be seen following treatment with a number of electromagnetic devices such as ultrasound, radiofrequency, lasers, light-emitting diodes, and visible light, as well as secondary to microdermabrasion.

      Postinflammatory hyperpigmentation is caused by 1 of 2 mechanisms that result in either epidermal or dermal melanosis. The epidermal inflammatory response (ie, dermatitis) results in the release and subsequent oxidation of arachidonic acid to prostaglandins, leukotrienes, and other products. These products of inflammation alter the activity of both immune cells and melanocytes.

      Epidermal melanocytes are stimulated, causing them to increase the synthesis of melanin and subsequently to increase the transfer of pigment to surrounding keratinocytes. Dermal melanosis occurs when inflammation disrupts the basal cell layer, causing melanin pigment to be released and subsequently trapped by macrophages in the papillary dermis.
      .
      Postinflammatory hyperpigmentation tends to fade with time and therapy. Epidermal hyperpigmentation may persist for indefinite periods, typically 6-12 months, after the initial inflammatory process resolves. Dermal postinflammatory hyperpigmentation may persist for years

      The treatment of postinflammatory hyperpigmentation (PIH) tends to be a difficult and prolonged process that often takes 6-12 months to achieve. Each of these treatment options potentially improves epidermal hypermelanosis, but none is proven effective for dermal hypermelanosis.

      A variety of topical treatments have been used to treat epidermal postinflammatory hyperpigmentation. These include hydroquinone, tretinoin cream, corticosteroids, glycolic acid (GA), and azelaic acid.[5] Lightening of hyperpigmented areas may be achieved with one of the previously named topical agents; however, a combination of topical creams and gels, chemical peels, and sunscreens may be necessary for significant improvement.[6] They are only effective for epidermal hyperpigmentation.

      (As mentioned above, we would recommend an anti-inflammatory topical product such as AnteAGE Serum as part of any regimen that includes potentially inflammatory reactions such as chemical peels.)

      Topical tretinoin 0.1% has been effective in treating postinflammatory hyperpigmentation. GA peels, in combination with tretinoin and hydroquinone, are an effective treatment of postinflammatory hyperpigmentation in dark-complexioned individuals.[7] All-trans retinoic acid aqueous gel 0.1-0.4% may be applied concomitantly with hydroquinone–lactic acid ointment for bleaching. Topical azelaic acid, which has been approved for the treatment of acne vulgaris, is useful for postinflammatory hyperpigmentation. In acne patients who are prone to postinflammatory hyperpigmentation, azelaic acid may be a good treatment option. The efficacy of tazarotene 0.1% cream for the treatment of dyschromia associated with photoaging and for acne vulgaris may also be beneficial, particularly in people with dark skin tone. Early and efficacious treatment of acne in patients with dark-toned skin helps minimize pigmentary abnormalities.

      Depigmenting agents abound in a variety of formations. Aloe vera leaf extract and its active ingredient aloin are considered potent skin depigmenting agents. Delivery too can be important. Glabridin microsponge-loaded gel may be beneficial in treating hyperpigmentation.

      Monobenzyl ether of hydroquinone should be avoided because of the risk of disfiguring depigmented patches of skin either at the application site or at distal cutaneous sites.

  6. Sadique Ansari says:

    Hi , I have PIH in the form of dark spots on my face left behind by chickenpox . Its been 40 days since I contacted chickenpox. Is it possible for these brown spots to fade away on it’s own? If yes , how long does it normally take ?? Please help.

    • drgeorge says:

      Dark spots from any injury, including chicken pox, can last months or longer. One determinant will be the depth of injury since epidermal dark spots are easier to resolve than dermal due to the continuous shedding of keratinocytes in the epidermis. “Trapped” melanin in the dermis does not have the same shedding phenomenon in play. Assuming chicken pox lesions involve at least some of the dermal layer, the resolution may take quite a while.

      Certainly sunblock should be routine to prevent solar radiation stimulation of melanocytes. Topical lightening products can be considered. By all means, keeping inflammation subdued after any injury during healing will go a long way to preventing PIH. It’s too late now, but I wonder if daily routine use of products containing anti-inflammatory growth factors and cytokines might have had preventative benefit.

      • Rashmi says:

        I developed shingles on my face and the rash has healed, forming scabs. Four days ago the scabs finished falling off and now I am left with post-inflammatory hyperpigmentation. Can you please let me know if this will eventually fade away on its own??

        • drgeorge says:

          We published a blog on hyperpigmentation which you can find at this URL: http://barefacedtruth.com/2013/06/14/postinflammatory-hyperpigmentation/

          Hyperpigmentation is a difficult problem, one that can be stubborn with improvement usually taking weeks to months. Please take a few minutes to read the blog post as it has helpful information.
          We are very aware of the impact hyperpigmentation has on people and currently have a “brightening” microneedling product available through our aesthetician network. A new AnteAGE MD product that specifically addresses pigment issues will launch soon. Please contact us if you care to learn how to obtain these services and products. We hope your issue resolves quickly. Keep us informed, please.

  7. Kelly says:

    Just started my Ante Age duo. Is it okay to layer Obagi 5 blender with Refissa over duo at bedtime?
    Thank you for your help.

    • drjohn says:

      Kelly, you can, but I wonder if you wouldn’t be better off doing the bleaching chemicals during the day and letting AnteAge do some repair and restoration at night. Obagi bland contains either 4% hydroquinone or 7% arbutin (depending on whether it is fx) as a whitener. Both contain multiple parabens. These are harsh chemicals. AntiAge is so anti-inflammatory it may even neutralize some of the bleaching effects. It works that way on strong acid peels – actually prevents peeling. That’s a good thing, but can be confusing. best to separate it out by at least an hour. AntiAge also brightens, but does so without strong chemicals. Refissa (tretinoin) is fine.

  8. Pila says:

    Hi drjohn,
    Thanks for ur info.
    I was being treated with chemical peels for dark periorbital skin which lead to 1*1cm dark patch below eyes..my moron doctor treated that patch with laser in span of 10 days which lead to aggrevating of patches..on detailed check up, it s showing dermal pih. I have tried almost all things from azelaic acid, vit c, kojic acid, hydroquinone..but none has been effective at all..
    Kindly advice me treatment as it s causing a lot of problems.
    Thank u.

  9. Pila says:

    Hi drjohn,
    Thanks for ur kind info.
    I was being treated with chemical peels for dark eyes which resulted in postinflammatory uneven dark patch below my eyes. My doctor tried to treat ths patch with laser in span of 10 days of chemical peels which lead to aggrevating of pih. On detailed examination it showed to have dermal pih. I have tried all topical medications but none have improved my symptoms..kindly suggest something.

    • drjohn says:

      Pila, the problem is inflammation. PIH, pure and simple. The peel caused your skin to be inflamed, and the laser just added to that. I would recommend AnteAge serum (highly anti-inflammatory stem cell cytokines) on the affected area to put out the fire. Melanin production should be downregulated. It may take a few months. Please take some good close up pictures before and after. If it doesn’t work you can ask for your money back. If it does work we will ask you for permission to use them in our lectures to other doctors, and offer you free product in return. How can you lose with that proposition?

      • Stan says:

        Last year I developed hyperpigmentation under my eyes following filler injection into my tear troughs, followed by filler removal. My left eye has cleared up completely, but the pigmentation under my right eye has not improved. As I understand it, dermal hyperpigmentation has to resolve on its own, usually over the course of a very long time. So I’m wondering if its dermal, and what I can do about it. You have mentioned your products as being of potential benefit.

        • drgeorge says:

          Hyperpigmentation is one of the most common reasons that people of color (African Americans, Hispanics/Latinos, Asian, Native Americans, Pacific Islanders, Middle Eastern groups) seek dermatologists’ help. Unfortunately, excess pigment can occur following any type of inflammation, whether from trauma, infection, burns, aesthetic treatments, sun, tanning beds or response to filler placement and removal. As to why one under-eye area cleared up and the other did not, your suggestions that “dermal” melanin may be the reason is interesting but not something so easily explained. Only a biopsy can sort this out although epidermal and dermal excess melanin (“hypermelanosis”) do have different appearances. Epidermal hypermelanosis appears tan, brown, or dark brown and may take months to years to resolve without treatment. Hyperpigmentation within the dermis has a blue-gray appearance and may either be permanent or resolve over a protracted period of time if left untreated. As to your question about use of our products being of benefit in managing your condition, we have many favorable reports from users with pigment issues. Keeping inflammation “tamped down” makes sense as a preventive strategy to help prevent melanocyte stimulation. If you do want to try our products, contact us and we’ll get you in touch with the appropriate people. We do provide BFT readers with a discount and a satisfaction guarantee.

  10. Katie says:

    I was reading about “post-inflammatory erythema” (PIE) the other day – apparently it is important to distinguish PIE from PIH (the former is red, the latter brown/purplish) because PIE is something to do with dilated blood vessels, whereas PIH is melanin-related.
    The article I was reading said that because PIE has nothing to do with melanin, it can’t be treated topically like PIH can, and will only respond to laser treatment.

    What do you make of this? Is it nonsense? I can’t find much elsewhere on “PIE”.
    I found it disheartening to say the least. I’ve spent the last year using L-AA, niacinamide, arbutin, tretinoin, and glycolic (keeping the tretinoin, niacinamide and L-AA constant, alternating the glycolic and arbutin) in a bid to clear up my red post-acne marks with no luck

    • drjohn says:

      Katie – we are familiar with the term “post-inflammatory erythema” (PIE) as it is commonly applied to the residual redness that occurs in the context of acne vulgaris. However, the term is an obvious misnomer, since redness is itself a cardinal sign of inflammation. It is not really “post-inflammatory erythema” but simply “inflammatory erythema” because the inflammation has not stopped – it is still smoldering on. Which should surprise no one, since acne is an inflammatory disease at its core. Just measure the cytokine profile in facial skin of an acne prone person – it is quite inflammatory even between eruptions. IL-1 is particularly implicated in acne pathophysiology. Along with IL-6, IL-17, and TGF-beta1. There is also involvement of vascular growth factors like VEGF and PDGF, which promote capillary growth.

      Yes, it is nonsense that the inflammation of acne (or any other skin redness) cannot be treated topically. Avoid steroids – add anti-inflammatory cytokines and growth factors. We are doing a study with skin redness from several causes right now using that approach, and are working specifically on an acne product that combines this with boron-based anti-inflammatories as well as probiotic recalibration of P. acnes strains to deal with the microbiology of acne.

      Good paper on inflammation in acne: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/pdf/jcad_6_9_27.pdf

      I would worry about using acids, arbutin, and tretinoin simply because these molecules can be irritating and can potentially add to the inflammation problem. Besides which they are more geared to help with late PIH melanin than redness. I also worry about laser for similar reasons. There is some evidence that combining microneedling (0.25mm) with topical approaches has value. Hope this helps. Good luck.

      • Katie says:

        Thank you for your (very informative) reply! It makes sense that my red marks are a sort of residual inflammation, I do have a very “easily offended” skin. Unfortunately the tretinoin is non-negotiable at the moment as it is the only thing keeping my acne at bay, but I will heed your advice and drop the others.

        I have been considering laser treatment for my rosacea (permanent diffuse redness, red wine-related flushing episodes, and little red spots around my nose and chin – though I’m not sure if they’re part of the rosacea or if they’re something like perioral dermatitis). Would you suggest I hold off until the post-acne red marks fade?

        Also, where might I get some of these anti-inflammatory cytokines and growth factors of which you speak? And do you have any other recommendations for reducing inflammation? Thanks again for a really helpful response! Just found your blog and am really enjoying the reading.

        • drjohn says:

          Katie, we are in clinical trials with a redness product (rosacea being the main indication) in the US, and have a slightly different version of the product being tested for the UK. I believe it will be available early next year. There is also a product aimed specifically at acne that is anti-inflammatory. The core of the product os the same cytokines and growth factors present in AnteAGE serum (anteage.com).

  11. Eugenia says:

    I was wondering where the stem cells in AnteAge come from? Are they donated by humans? Thanks!

    • drjohn says:

      Yes, they are indeed human, which is why the products work so well on humans. Plant stem cells work on plants only. They are provided by paid volunteers, generally between 18-24 years of age, typically college students. They are paid ~$400. The procedure is done under local anesthesia, and causes only minimal discomfort. All donors are also extensively screened with blood tests to assure they are disease free. One marrow sample provides enough cells to make abundant cytokines and growth factors for skin rejuvenation.

  12. Susan says:

    Dear dr john
    I had gone for laser treatment for some not very obvious pigmentation on my cheeks. The pigmentation got really bad after the treatment and my doctor said it is due to PIH. We have so far used triluma, hydrocortisone, azelaic cream but none has worked so far. Had 2 more rounds of laser but the hyperpigmentation didn’t get better.
    I can’t even talk to people without thinking that they are staring at my ugly cheeks. I am Asian- Chinese. Please help 😞.
    Thank you

    • drgeorge says:

      Susan, PIH is indeed a major issue with certain skin types, especially when it occurs regardless of the cause of the inflammation. It is particularly irksome when a treatment intended to improve the situation actually makes it worse. In your case, topical agents have not been helpful. Here’s a thought you may want to give consideration: microneedling in conjunction with topicals that are well proven to reduce inflammation. We try not to be too commercial on BFT but have abundant evidence that our technology might be helpful. We developed a microneedling solution that has proved efficacious in reducing the inflammatory phase of healing, and our serum/accelerator products have helped MANY users who have inflammatory skin conditions. According to one of our long-term re-seller partners (a medical spa in New Mexico), all of their patients are instructed to use our serum/accelerator for one to two weeks before any aesthetic procedure. Subduing sub-clinical smouldering inflammation prior to treatment makes great sense, especially if the patient is prone to PIH. The products are continued after procedures.

      Below is the URL from a Google search of patients treated with microneedling for pigment issues. We don’t know the details of the photos but many show impressive improvement. If you are interested, please contact us again and we can explore ways to provide product to see if this approach is helpful. We would recommend a test area be treated first to see how your skin responds. You will need to find a local provider for treatment. Feel free to contact us again and we’ll communicate directly outside BFT.

      https://www.google.com/webhp?sourceid=chrome-instant&ion=1&espv=2&ie=UTF-8#q=use+of+micro+needling+for+hyperpigmentation

  13. Joanne says:

    Please can you advise me… I had restylane dermal filler to my chin / lower mouth area. I did bruise in these areas which went away after just under a week, however, now I seem to be developing dark areas in the same place which looks like PIH. Is this common after fillers as it’s never happened to me before? Also is it better to just leave things alone or better to start now with a cream. I don’t want to irritate the area but want to understand if the sooner I start with a cream ? Hydroquinoin the less chance of the area getting darker. I had the filler ten days ago – thx for your advice…

    • drgeorge says:

      Bruises result from capillary rupture and leakage of blood into tissues. The progressions in color changes occurs slowly as the hemoglobin is slowly metabolized and reabsorbed. We are all familiar with the blue to green to yellow transformation that slowly occurs. Full resolution can take several weeks so incriminating PIH may be a little premature. Certainly inflammation following trauma is to be expected, although it resolves relatively quickly after bruising. Bruises are tender for a few days and then typically are painless despite the fact that discoloration is still present. Certainly, if PIH is something you have dealt with previously, it would be more of a problem. We can’t give medical advice for your specific situation so it would be best for you to consult the person who did the filler injection.

  14. Rose says:

    Hello.

    Any pertainable information you can offer to me would be greatly helpful…..
    Exactly 3 months ago, I was accidentally severely burned by a co-worker, who accidentally burned me all over my mid and lower back. We were working inside of a coffee food truck, and he accidentally severely burnt me with a commercial hot water kettle and it’s contents that was scalding hot and had just been taken off the boiler. When he accidentally rammed into me from behind with the scalding kettle, the scalding boiling water also all poured out from the large kettle and all over onto my back. I was then rushed to the ER, etc. However, I am left with a large scale, (covers a large area) of a flat pinkish burn scar all over my back. There are some thumb size marks that are now a brownish color. While the overall larger affected area is still pink inside but with a brownish framing around it.

    Will this overall pinkish color ever fade? It has faded somewhat in this 3 months since the injury,…. But there is still this large scale overall mark. Also, on some parts of the scar, the skin now feels slightly gritty, like finely milled sand paper. I was told by the Burn doctor and Nurse to give the area like a year to heal overall. I’ve been massaging different oils onto the scar everyday for like an hour, hoping this will help it to penetrate deeper into the skin to help it heal. I’ve been also focusing on nutrition and supplements to help create an overall healing nurturing environment within my body.

    Is there any specific topicals I should be applying right now, that you could recommend? Any insight you could provide toward this scar healing would be deeply appreciated.

    Thank you,
    Kindest regards

    • drgeorge says:

      Wow, Rose, what a tragic accident. So sad. I hope the information below is helpful.

      We do understand your concerns and appreciate your question. We’ll be brief here but a post or two about burns would be helpful (interesting?) for our readers so expect to see something on BFT in the near future.

      The scald burn you describe occurs at over two hundred degrees Fahrenheit. With very brief encounters and small volume of water, one would see 1st degree burns (erythema i.e. redness and pain). With longer exposure and larger quantities of water, 2nd degree burns in which skin blisters. With longer exposures to high temperature, 3rd degree burns where tissue death occurs. 3rd degree burns can be partial or full thickness.

      Burn healing is a dynamic process with overlapping phases. The initial inflammatory phase brings white cell to the site of injury to help combat infection, remove devitalized cells, and participate in the bio-signal cascades that initiate the proliferative phase where cell multiplication is dramatically accelerated. There are ramifications to these physiologic processes. What you describe, abnormal pigmentation and uneven surfaces / texture can be attributed to these processes, particularly inflammation.

      Inflammation (via the various cells and bio-signals involved) is well known to be directly stimulating to melanocytes (excess pigment produced), fibroblasts (excess collagen production), and abnormal maturation of tissues, with long-term effects on remodeling. The pink color can persist for quite a bit of time. Increases in blood flow from new capillary structures, and dilated vessels as healing occurs, make the red color of blood show through as increased pink. Also, loss of the epidermis, and the keratinocytes that comprise much of it, removes the “storage sites” of the skins pigment. Melanocytes produce it / keratinocytes take it into the cell structure, where it remains until that cell eventually sloughs off. If you lose a lot of cells due to a burn, re-pigmentation can take quite some time, and may well never be normal. (Remember melanocytes sometimes stop working.)

      As for topical products, I would recommend only products with PROVEN benefit to skin based on published medical research. Massaging oils into the skin will help keep it well hydrated and the physical forces may help keep collagen softer. Our first suggestion, and you can’t start too soon, is to do something to help manage inflammation, i.e. quench it.

      We know this is tooting our horn, something BFT was not created to do, but we feel AnteAGE or AnteAGE MD Serum (and to a lesser degree Accelerator) may be of considerable help. We base this opinion on several important observations: 1) AnteAGE and AnteAGE MD Serums consistently reduces facial redness and has proven time and again to be effective in managing rosacea and seborrheic dermatitis; 2) “down time” and recovery following fractional carbon dioxide resurfacing has been repeatedly and predictably shortened by up to 40%; 3) acute inflammatory flare ups from a variety of skin conditions have subsided in remarkably short time. I truly wish you had written us earlier…but better now than never.

      In preparing to answer your inquiry, I took a second to see what I could find on the internet that I might not have yet seen (we are always learning at BFT, thanks in part to our readers.) It turns out our old friend, the bone marrow mesenchymal stem cell (the same ones we culture to make the hero ingredient in our products) has proven effective in burn wound healing. Quoting below from the article:

      “Addition of bone marrow stem cells to non-healing chronic wounds leads to engraftment of cells and enhanced wound healing. Moreover, studies have reported that bone marrow stem cells can transdifferentiate towards multiple skin cell types. Mechanisms of action of bone marrow stem cells in burns are not fully elucidated, but modulation of inflammation has occurred after radiation burns in humans.”

      Rose, I hope this was helpful to your understanding. Please feel free to contact us if you would like to try some of our product to see if it helps.)

  15. Chris says:

    Hello,

    I have developed PIH at the underarm area due to hair removal by plucking for many years now. The color of the PIH is grayish – blue and based on what I read from other websites, this seems to be a dermal PIH? I went to a dermatologist that prescribe me 4% HQ and have been using that for 3 months with minimal improvement. My dermatologist told me to do IPL instead, but I am afraid of other possible side effects since my skin is extremely prone to PIH (not only in the underarm area but also occur in other places as well).

    Is there any other ways to remove melanin from the dermis? In some websites that I have been searching they mentioned that it may be permanent, is this true? Will this kind of PIH resolve by itself overtime? If it does, how long will it normally take?

    Thank you for the insight and information.

    • drgeorge says:

      Darkening of axillary skin as a result of repetitive trauma from shaving and plucking is more common in darker skin type people – Fitzpatrick types III – VI. In searching the literature, there is a particularly high incidence among Southeast Asian women. A research study of Filipino women, including punch biopsies, confirmed the darkening was indeed a form of post-inflammatory hyperpigmentation caused by repetitive trauma. Mononuclear cells and phagocytes ingest the excess melanin, essentially “locking” it in place. Incriminated in the process was the negative effects of trauma upon the skin barrier which sets the stage for a chronic inflammatory response. Treatments include cessation of the inciting trauma and topical products that help restore the skin barrier. Among these are glycerol and sunflower seed oil. Topical 4% niacinamide and .05% desonide (a topical steroid) have anti-inflammatory effect and have been shown effective. Of the two, niacinamide can be purchased without a prescription. The steroid preparation, however, was marginally more effective. References below.

      http://onlinelibrary.wiley.com/doi/10.1111/j.1468-2494.2012.00729.x/full

      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552481/

  16. KIm says:

    Can you please provide assistance?
    I am a 40 year old woman of middle eastern descent who had a sublative/ematrix procedure for tightening/anti aging my skin. Prior to the procedure I had a clear complexion, even skin tone but prone to being very sensitive.
    After the procedure during the healing my skin was very agnry, red and hot. It stayed very red and hot for about 4 weeks even after the grid marks had healed. I am now 6 weeks from the treatment and I have blotchy pigment and hyperpigminted in some areas on my cheeks.
    I just started using a .25% renina and a 2% hydroquinone and mild gycolic acid wash but seems like my skin is back to being red and irritated now in addition to the hyperpigminatation.
    I religiously use sunscreen but living in Florida we spend a lot of time outside,
    I am so upset that I had this procedure because now I feel like I will never have my complexion back. It dominates my every free minute as I am trying to research solutions. I am so glad I found your website and the community around this problem.

    I would be so grateful for your expertise.

    • drgeorge says:

      “Safe Resurfacing – For All Skin Types and Colors‎” – that’s what one reads when Sublative Ematrix is Googled, although in your case, something is not going according to plan. After significant experience with another competitor’s RF microneedling device, it should be said that proper power settings on such machines are important to observe, particularly for darker skin types, and even so, individual skin reaction may be surprisingly varied. Your tale of angry, red, hot skin for four weeks make one ask what did you apply to your skin during aftercare? Improper choice in topicals can set the stage for nasty chronic inflammation, exactly what you seem to be describing. Skin permeability is greatly enhanced during the period of skin barrier disruption – the first few days following treatment in particular. It seems your skin is still inflamed and that is not a good thing. It sets the stage for fibrotic healing and hyperpigmentation.

      BFT is hearing a alarming number of distressing stories like this. By all means, you must rely on the professionals in your life as we do not practice medicine on this site. What we can say without equivocation, based on experience in our clinic and from many of our reseller colleagues, the products we developed have proved very helpful in preventing post-procedure inflammation, and in helping manage it, if it should occur. We recently tested our products in a IRB sanctioned trial and there was consistent reduced inflammation post RF microneedling when our products were used. In fact, one patient who was randomly assigned to the study arm without our products, had a very significant post treatment inflammation that persisted well past the time one would expect it to subside with or without treatment. She was started on our products and her inflammation greatly subsided overnight and was essentially gone two days later. Email or call to let us know if you would care to see if our products might be of help to you.

  17. Loading Hope says:

    Hi,
    After years of waxing my upper lip as my primary method of hair removal I was left with an increasingly pigmented area there. It look like a faint shadow of a mustache. I went to a dermatologist claiming to have experience working with my type v skin. I was prescribed hydroquinone 4% and applied it to the area 2 times daily, as per the instructions. After 7 days my skin was peeling and the area had darkened ten fold. I called the derm who told me to discontinue usage and that I had no other options for treatment. She said some issue are not resolvable,, implying that I would have to learn to live with it. I could no longer leave my home with using makeup (dermablend) although this doesn’t cover it 100%. People stare. I am embarrassed and feel helpless.

    I found another derm who seems to think he can help me. He gave me a cream that has alpha hydroxy acids. I used it nightly for a week. Then I started the prescription .05℅ desonide applied once daily at night while still continuing with the cream. In 4 weeks I am to go back for a superficial chemical peel. Does this seem like a logical course of action? Is there anything else I should be doing? (Outside of the obvious- daily photoprotection and sun avoidance as much as possible) Under this system, what is the average timeframe before improvements might be noticed?

    Given that the trigger for my melasma was waxing, should I anticipate that typical sun will cause flares ups (assuming this derm is actually helpful in clearing things up)? Is it likely flare ups will be as dark as the “rebound darkening” I am currently experiencing?

    • drgeorge says:

      Undesirable pigment changes from recurrent trauma in susceptible skin types is very commonplace, actually expected in people with darker skin types. Even minor trauma such as plucking and waxing results in an inflammatory response, setting the stage for melanocyte stimulation. The inflammation can be very subtle – not painful, not even associated with visible redness, yet the stage is set for a repetitive process that worsens discoloration over time.

      The fact that your dermatologist prescribed treatments made the problem worse emphasizes just how difficult this problem can be to manage. As to the current strategy, alpha hydroxyl acids to enhance exfoliation of superficial layers of the epidermis, 0.05% denoside (cortisone-like steroid) to reduce inflammation in preparation for a superficial chemical peel, sounds like a reasonable strategy. We wish you luck.

      There are a number of laser and IPL treatments available but be sure to go to someone who knows this field very well. Wave length and pulse duration are critical determinants in providing safe, helpful treatments that help, not worsen the problem. Lasers that are aggressive will cause more trauma, potentially making the problem worse.

      BFT has recommended our products (AnteAGE and AnteAGE MD) in past answers to readers’ questions about pigmentation, and hope this is not off-putting to our readership. Our desire is to inform about possible ways to reduce inflammation, which is the genesis of PIH. With several years of experience in laser recovery (up to 40% faster healing) and many instances of people being surprised their abrasion, burn, acne breakout etc. did not result in PIH when our products are applied, we feel you should know. Of course, the kudos go to the bone marrow stem cells we culture and the bio-signals they produce. Predictably anti-inflammatory. Let us know how it goes. Contact us if you wish to learn more.

  18. Amy says:

    Hi, I applied yellow peeling oil on my underarms almost 2 weeks ago and it peeled after 3 days of applying it. But it developed a very burning sensation and my skin on my underarm became very red and itchy. The morning after, I noticed that my skin on my underarms became super red and later in the day became brown and it darkeNed as in brown patches:( I was hoping that the peeling oil would help but it made my underarm thrice darker now. Will this brown burn spots go away? This is considered as PIH right? I’m wanting to try Hydroquinone creams but I want to make sure if this is not permanent? Will my old skin color come back? Please help and advise. It’s very embarrassing to show off my underarms now. I’m a Southeast Asian and I have a very fair skin so the dark spots left by the peel burn are so obvious.

    • drgeorge says:

      Super red means highly inflamed. If it goes from red to brown in hours, that is not hyperpigmentation but rather skin getting ready to slough. Is this skin peeling at all? I would hope you can settle the inflammation down a bit. Have you sought help? Steroids might help; our product I think would be helpful. If you’re prone to hyperpigmentation with inflammation, you need to quench the fire. Have you consulted your dermatologist?

  19. Nancy says:

    Hi – Dr. George and Dr. John – I am a darker-skinned Asian-American woman who had hyperpigmentation / PIH from acne in my 20s and also from overexposure to the sun. The spots were mostly on my cheeks near my eyes and also above my upper lip and also on my chin. I recently went to Taiwan to get laser treatment and IPL and, while some of the smaller spots are gone, most of them actually got darker/more brown and more pronounced. I am so sad and so afraid that I have done permanent damage. The doctor who performed the procedure said that I am going through PIH and that this is normal, and that my skin should resolve itself in a few months if I use hydroquinone, Vitamin-C, and sunblock on a regular basis. Is there anything you can prescribe or suggest? Can you tell me if her assessment is accurate?

    • drjohn says:

      Nancy – your genetics definitely make you more susceptible to PIH from anything that causes inflammation to your skin. IPL is effective, but has to be used cautiously. Laser even more so, because it can deliver enough energy to cause ablation of skin tissue resulting in more PIH. We tend to like to use IPL alone. The problem with hydroquinone is that it is irritating (inflammatory) like bleach and can leave skin spotty. Vitamin C is weak. Sunblock of course is always good to prevent further damage. What I would recommend would be to use skin care that is anti-inflammatory (like AnteAge or a balanced growth factor product). There are topical lighteners not based on hydroquinone that can also be helpful.

  20. Disheartened says:

    Hi Drs John and George,

    I’ve had chronic eczema around my eyes and mouth for several years now and had been treating it with Elomet and Bethamethasone.

    It’s been about a few weeks now since I decided to stop using the meds after I read online about the risks of developing glaucoma and cataracts.

    I’ve now noticed that I have PIH due to my constant vigorous rubbing of the skin to try and relieve the intense itching, dryness and burning sensation.Cold compresses throughout the day/night have helped provide some relief but I”m still suffering from disturbed sleep.Anti-histamines are’nt helping much either.

    I really hope you’ll be able to answer a couple of my eczema-related qns.They are:

    1.How can I treat the active eczema rashes without the use of topical steroids?

    2.The skin around my eye and mouth area is hypersensitive and has a dark brown/black discoloration.Is this dermal hyperpigmentation and is it permanent? What can I apply topically to reduce the discoloration without provoking an allergic skin reaction and thus worsening the existing skin condition?

    Thank you so very much.

    • drgeorge says:

      Eczema can be a chronic and stubborn condition to manage. Steroids, a common treatment, indeed do have associated complications making long-term treatment problematic. In fact, chronic use itself can lead to steroid induced dermatitis, which is an especially difficult problem to manage since steroids, the stand-by for reducing inflammation, is the causative agent.

      Restoring and maintaining normal barrier function is important in eczema, and reducing inflammation, and keeping it reduced, is critical in managing PIH (post inflammatory inflammation.) We do have a suggestion which requires us to toot our own horn. BFT readers already know that we have day jobs which are formulating, producing, and marketing hi-science skincare products, nearly all of which contain our hero ingredient, bone marrow mesenchymal stem cell conditioned media. These products have been in the marketplace for six years (AnteAGE brand) and four years (AnteAGE MD.)

      We are aware of many instances where our products have successfully managed eczema and reduced inflammation. The Serum & Accelerator combination has ingredients that have anecdotally been effective in reducing inflammation and managing eczema. You can visit anteage.com to learn more. If you are interested in trying these products, please let us know.

  21. Nadeem says:

    Sir I developed an allergic reaction after using Benzoyl peroxide and my face became red.After long treatment my facial redness went away.But I have now developed something which I myself don’t now.My face becomes black when I remain out of sun and when I go in the sun it turns red.please suggest me something.

  22. Janine says:

    Hello Drs., I have developed shingle on the scalp and forehead. Question 1 : Would the AnteAge microneedling solution (minus the microneedling of course) or serum help with the inflammation of Shingles (the sores and lesions) or is this something different that cannot be treated with cytokines.

    Also I am doing low level light therapy (red and infra red lights). Lots of research shows that it may reduce the postherpetic neuralgia. Question 2: What is your medical opinion using light treatment for neuropathy. What should the frequency of treatments be in order to see improvements in the pain? And can it remove the postherpetic neuralgia for good? Thanks for the guidance.

    • drgeorge says:

      Janine, so sorry you have to deal with this issue. Not fun. For readers who may not know, shingles (herpes zoster) is a vesicular (blisters) and painful rash that results from delayed “reactivation” of the dormant chickenpox virus (varicella-zoster) within cutaneous nerves, making it occur in distributions that follow the affected nerve’s pattern of innervation. It can occur anywhere but is particularly troublesome when affecting nerves of the face, especially near the eye. The incidence rate of herpes zoster ranges from 1.2 to 3.4 per 1,000 person-years among healthy individuals, increasing to 3.9–11.8 per 1,000 person-years among those older than 65 years. Herpes zoster affects an estimated 500,000 Americans each year. Fortunately, there is a vaccine that is quite effective in preventing shingles. It introduces a small dose of the virus, live and attenuated, to boost the body’s immune response against the virus.

      There is solid published evidence of efficacy for the use of light in treating shingles. see: https://www.practicalpainmanagement.com/therapeutic-laser-treatment-herpes-zoster

      Several Studies have been performed to determine the effectiveness of therapeutic laser on herpes zoster patients:
      • Moore treated 20 patients with post-herpetic neuralgia (PHN) who were un-responsive to conventional care and experienced pain for at least six months. This double blind study demonstrated that the placebo group experienced little change while the treatment group experienced a decrease in VAS pain levels from 10 (pre-treatment) to 2 (post-treatment).12
      • Moore published a retrospective report covering 300 patients over nine years and found that patients with cephalic zoster experienced 61% pain relief and thoracic zoster patients experienced 78% pain relief following laser therapy. Laser therapy was also found to be 28% less expensive.13
      • McKibbin treated 39 PHN patients with a GaAs laser. These patients had a visual analog scale (VAS) average of 8.5 before treatment and 3.3 after treatment. At one year it was 2.8.14
      • Hong reported that 60% of the PHN patients that he treated with laser therapy were pain free after one year. These patients had been unresponsive to conventional care.15
      • Hachenberger treated 41 patients with PHN, 93 herpes simplex patients and 3 herpes genitalis patients. All responded well to laser therapy.16
      Iijima treated 18 patients with PHN. VAS decreased from 6.2 to 3.6. Pain intensity decreased from 100 to 44.6%.

      I am not aware of anyone who has tried our Serum or Microneedling Solution in treating shingles but the idea does have merit. We know our products are quite effective in reducing inflammation and time of healing after laser resurfacing, RF microneedling and other aesthetic procedures. It seems it is worth a try. BFT sees no downside to such a trial. Let us know how we can help.

  23. Janine says:

    Thank you for replying Dr. George. Would you mind answering a few more questions please. I developed the rash 10 days ago and only got a diagnosis 3 days ago. The forehead rash has not blistered and no oozing so far so I think applying the solution and serum has helped. It is difficult applying products to scalp blisters and very messy. I have not applied anything for the scalp but would you recommend I dilute one vial of microneedling solution (1.5ml) in Hyaluronic acid for the scalp blisters?
    My light therapy is 30 minutes per treatment X 5. It was suggested we then spread them out twice a week. What do you think about the frequency of tx and how long should I continue? Would the pain and itch be an indicator that I need to continue with light therapy treatments?
    Thanks,

    • drgeorge says:

      Janine, my comments should not be considered medical advise. That you need to get from your physician. That said, in reviewing the literature, some recommendations are consistent from many sources. Antiviral medications have a role in the early onset of symptoms and may help reduce the severity of the outbreak. NSAIDs (non-steroidal anti-inflammatory drugs such a Aleve, Motrin, Advil) can be helpful with pain and inflammation. Topical corticosteroids can help reduce inflammation and can be gotten over-the-counter or by prescription. Of course, we continue to think our products offer an attractive alternative since they have proven to reduce inflammation. You don’t need a lot so the roller-ball vial microneedling solution applied (even on the scalp) three or four times a day should suffice.

      As far as light treatment goes, it sounds like the plan to treat you five times over the course of 2.5 weeks is reasonable. One impressive result I saw in an internet article was the result of four treatments over two weeks. Pain should improve as the healing progresses, and itch is a common symptom that may indicate the worst is over. Good luck!!

  24. Blantina says:

    Hi Dr George, I hope I can get help. I am an african lady aged 30 and in march I had a lactic acid peel on my hand. After the peel, my skin was fine and i was happy but 2 weeks later I darkened terribly and my skin’s texture changed and became rough. I went to a dermatologist who prescribed 5% salicylic acid, 3% hydroquinone mixed in betamethasone ointment. I used the ointment and the pih cleared, however when I stopped the treatment my hand turned black again now I dont know what to do anymore. Ideas?

    • drgeorge says:

      Unfortunately, unwanted pigmentation is always a risk of all skin procedures for people with darker skintypes (Fitzpatrick 3, 4, 5, 6) and the darker the skin, the more likely post-inflammatory pigmentation is to occur. The skin may respond to any insult, whether intentional by an aesthetic treatment, or accidental through burn, trauma, or infection with stimulation of melanocytes and deposition of increased undesirable amounts of melanin. Remember, the skin has a very small repertoire or possible reactions – increased pigment or increased collagen deposition (fibrosis and scars.)

      The most common cause of increased skin pigment (and skin damage of all sorts) is, of course, solar radiation so regular and judicious use of sunscreens is something every person should practice throughout life, regardless of skin type. Topical tryosinase inhibitors that interfere with the cellular synthesis of melanin include hydroquinone, azelaic acid, kojic acid, arbutin and certain licorice extracts. Other depigmenting agents include retinoids (vitamin A), mequinol, ascorbic acid (vitamin C), nicacinamide and N-acetyl glucosamine. Your dermatologist is your best source for such products.

      As our readers know, we are great fans of topical anti-inflammatory growth factors and cytokines, both as a preventative and therapeutic modality. We have seen our bone marrow stem cell derived conditioned media products prove to be effective in preventing and helping improve PIH. For this reason (among others) a growing number of physicians are using our products as topical agents in preparing the skin for aesthetic treatments, because they reduce pre-existing indolent inflammation as well as help the skin quickly exit and reduce acute inflammatory responses. We are aware of successful use with fractional CO2 laser resurfacing, RF microneedling and microneedling. PIH is a difficult problem to deal with after it has occurred. We are convinced preventing as much inflammatory response as possible goes a long way in producing desirable aesthetic results.

  25. Angela Beighton says:

    I had a plasma eye lift 3 weeks ago which initially healed well and the skin was pink. It progressively got darker and is now a light to dark brown in places. My Dr has diagnosed post inflammatory hyperpigmentation and has suggested azelaic acid and phytic acid (not hydroquinone round the eyes) to help. I’m concerned that there might still be some inflammation from the original trauma and that the suggested treatments might aggravate it more. Any suggestions?

    • drgeorge says:

      Plasma eye lift involves the use of pinpoint high energy heating of the eyelid in a closely placed pattern which leads to collagen contraction. Being burns, however, also means the healing process will begin with an inflammatory phase that in people with darker skin types can lead to significant pigmentation. Like all “controlled” energy delivery to the skin, the risk of untoward pigmentation is greater in higher Fitzpatrick skin types. You can see the procedure performed at:

      https://www.youtube.com/watch?v=y4pV8n4Z1Dc&t=84s

      Our opinion is that use of products that moderate inflammation from the outset can be beneficial in preventing the problem. From personal experience and knowledge based on years of use of products containing conditioned media derived from bone marrow mesenchymal stem cells, we are convinced that immediate use of such products can help avoid post-inflammatory hyperpigmentation (PIH.) Once the melanin has been produced, resolving it can be a challenge.

      Topical application of tyrosinase inhibitors such as hydroquinone, kojic acid, arbutin and others can help lighten skin. Steroids, vitamin C and vitamin A (Retin-A, retinol, etc.) also can be helpful. Be sure to consult your dermatologist and follow his/her advise, especially about what is safe to use around the eyes. If you plan to have additional energy based treatments, you may want to use products containing bone marrow stem cell conditioned media to help nip the problem in the bud (we can recommend AnteAGE or AnteAGE MD microneedling solution of Serum) An ounce of prevention….

  26. Rimavh says:

    Docs, can Anteage MN solution help with bruising resulting from fillers (in this case around the lips of a client who has gotten fillers a week prior to her daughters wedding. She has been using AnteageMD for a couple of weeks daily 2x from me, but the injectables she got elsewhere. I have recommended LED light tx and Arnica (iffy on the Arnica but can’t hurt) but wondered if I gave her a roller ball of the MN solution to apply in addition to the her daily serums, would that expedite healing? She has 6 days and is very purple.

    Btw, I stabbed myself with a scalpel (by mistake) and was too busy to get to a doc or ER for stitches despite how deeply it penetrated. I used butterfly plasters, my anteageMD MN solution and an Omega 6 balm. By the time I got to the doc a week later the wound had healed beautifully from the inside out but the gap where the skin could no longer be pushed together is a bit bumpy and uneven. I tell you this because I was thrilled to see the healing. I imagine if continuing to apply the MN solution will continue to improve it. Is there a point where it’s a waste b/c the needling solution won’t penetrate (without needling!) and I should switch to using Step 1?

    As always, grateful for the learning and healing I get from you.

    • drgeorge says:

      First, in response to your question about AnteAGE Microneedling Solution as an aid to speeding the resolution of bruising from filler injections, it is difficult to see a physiologic rationale for why that would be helpful. However, there is abundant evidence to recommend it for application to an acute injury to the skin due to its pro-healing, anti-inflammatory effects. A plastic surgeon who used it on a laceration on his forehead (a surfing accident that he stitched up at home looking into a mirror!) send us a video of his wound six days post closure and said the results were “amazing.” The bio-signals in MNS are similar to what is in our Serum, so one should expect the same benefits on healing. The Serum is not intended for use with microneedling and makes more sense for application to healed skin.

      About bruising:
      A bruise occurs when small blood vessels rupture and blood leaks into surrounding tissue. It happens most commonly in skin, fat and muscle, but can occur in nearly all tissues. The medical term for a bruise is contusion and the colorful aftermath ecchymosis. It can easily result from injection of fillers if the needle injures a vessel. Bruises from contusions usually have associated tenderness and swelling for the first few days but are painless for most of the resolution period which lasts about two weeks. Ecchymosis related to needle injury are typically painless. If a bruise is painful, acetaminophen rather that aspirin should be used since aspirin can incrase bleeding

      During resolution, hemoglobin, the iron-containing protein within blood cells responsible for oxygen transport, undergoes metabolic degradation and removal. Hemoglobin is first broken down into iron and a greenish pigment call biliverdin. Biliverdin is eventually converted into the orange pigment bilirubin, which is excreted via the liver into the bile. Additional metabolism of bilirubin within the intestines results in mesobilirubinogen and urobilogen. Some urobilinogen is reabsorbed. Further metabolic degradation yields urobilin, the pigment that colors urine yellow, and stercobilin, the pigment that makes feces brown.

      Ecchymos is first reddish but quickly turns bluish-purple or even blackish as it loses its oxygen. 5 to 10 days later it will appear greenish or yellowish (biliverdin.) From 10 to 14 days it turns yellowish-brown or light brown, and soon fades away.

      To minimize bruising, one must minimize blood leakage into tissues. Ice packs lower tissue temperature which causes local vasoconstriction. Ice should not be applied directly and be removed for a few minutes every 10 minutes of application. 48 hours after the bruise, warm compresses will help increase local blood flow to aid in pigment removal.
      Arnica montana, an herb in the sunflower family, has been shown to reduce bruising in facelift patients when used twice daily for two weeks. It does have anti-inflammatory properties but is a contact allergen in many people. It is important to note that preventing bruising is not the same thing as speeding up resolution.

      Treatments with pulsed dye laser may be helpful but the studies have conflicting results. (See references below.)
      I could find no conclusive studies confirming efficacy of the several bruise products on the market. If any BFT readers are aware of studies that confirm topical products in bruise resolution, please let your BFT host know. We always like to learn.

      Finally, a bruise may be a cause for concern if the following occur:
      Pain persists past three or four days.
      A lump develops around the bruise.
      Bruises occur with little or no trauma.
      You see blood in your urine or feces.

      Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L. Exp Dermatol. 2008 Oct;17(10):849-57.
      Comparative study on bruise reduction treatments after bruise induction using the pulsed dye laser. Dermatol Surg. 2013 Oct;39(10):1459-64.
      “Our study showed no significant difference in cold compress, hydrogen peroxide, and over-the-counter serum in reducing time to bruise resolution. PDL therapy resulted in greater bruise severity scores and increased time to bruise resolution when used soon after bruise induction.”

      Pulsed-dye laser for treating ecchymoses after facial cosmetic procedures. Arch Facial Plast Surg. 2009 Mar-Apr;11(2):99-103.
      “Treatment with the pulsed-dye laser is safe and effective for expeditious resolution of postoperative ecchymoses after facial cosmetic procedures. It has the potential for wider application in treating postoperative ecchymoses on other areas of the body and after trauma.”

  27. Mariana Seyara says:

    I have had a rash on my ankle as a result of an adhesive plaster I wrapped around it for several days. The inflammation was treated with a topical steroid cream (Mometasone Furoate) for 8 days. The inflammation and itching have gone, but now the rash has become dark brown, and the color has not changed for 3 weeks. I am using hydromol ointment and Aloe vera…but the color is the same. What can do?

    • drgeorge says:

      We take it that your use of the term “adhesive plaster” refers to an adhesive bandage which can vary in construction, typically with a plastic or fabric backing. Your rash may indicate an allergy to some component of the bandage including the adhesive. Nonetheless, it sounds like the rash which resolved with the medium strength topical steroid, mometasone furoate, was of sufficient degree and duration to result in post-inflammatory hyperpigmentation (PIH). It is conceivable, although three weeks is a fairly long period of time, that the residua of the rash is a thickened layer of discolored keratinocytes that may spontaneously desquamate (“peel”) over time. Hydromol is helpful in restoring or retaining skin hydration as it contains sodium pyrrolidone carboxylate which penetrate the stratum corneum, helping it absorb and retain water. Liquid paraffin, another ingredient, provides a layer of oil and help sooth and soften the skin. If the cause of the darkness is increase melanin in the deeper layers, it may take a long time to resolve.

      BFT published a post on PIH a while back at the URL http://barefacedtruth.com/2013/06/14/postinflammatory-hyperpigmentation/
      We suggest you take a look at that and you will learn about how this condition occurs and what can be done about it. PIH is more common in darker complexions and a surprisingly small amount of inflammation can set it off in susceptible individuals. Good luck and let us know how this goes.

  28. Anita says:

    I have a severe case of erythema nodosum, I am on my 3rd week and as my older bumps, (still have new ones coming daily), turn purple I wanted to know if I could apply something topically now, that would make it less likely to have permanent hyperpigmentation. I am caucasian, tend to heal slowly, and also have melasma (on my face) from my 1st pregnancy 8yrs ago (just to give a snap shot of my skin type), dermatologist’s have told me I have very sensitive skin. It would be nice if there was something I could apply topically to help prevent hyperpigmentation, and even be anti-inflammatory, and possibly pain relieving. I have not discovered the trigger of the erythema nodosum, I’ve had blood tests and a biopsy, waiting on results. Just wondering of there is something I could be doing now? My lower and upper legs are covered…. Thank you in advance!!

    • drgeorge says:

      Certainly, you need to follow your physician’s advise with regards to management and treatment of your erythema nodosum. That said, erythema nodosum is a condition that causes painful red bumps under the skin, typically on the shins but also sometimes affecting the ankles, knees, thighs, and forearms. The condition is one of the most common forms of a rare inflammatory problem called panniculitis, which is inflammation of the subcutaneous fat under the skin.

      Most cases occur in people between the ages of 20 and 45 years old with women five times more likely than men to develop the condition. The condition is usually relatively harmless, but it can be a sign of an underlying infection, other inflammatory conditions, or an abnormal response to an allergen or medication.

      Researchers are not entirely sure how EN develops. One theory is that it may be caused by the buildup of immune complexes in tiny blood vessels and connections in the subcutaneous fat. These buildups lead to inflammation. Because of the depth of the lesions, located deep to the dermis, the effect of topically applied products may have limited effect on deeper tissues.

      Common treatments include:
      • bed rest, especially if swelling and pain is severe
      • changing any medications that cause EN, but only at a doctor’s discretion
      • applying ice wrapped in a towel to the affected area for 15 to 20 minutes at a time, several times daily
      • elevating the affected area using a prop, such as a pillow
      • over-the-counter pain and anti-inflammatory medications
      • light compression stockings or supportive bandages and wraps
      • oral tetracycline
      • potassium iodide, often 400 to 900 micrograms (mcg) per day for 1 month when symptoms begin
      • systemic corticosteroids, often prednisone
      • steroid creams

      You mentioned concerns about post-inflammatory hyperpigmentation. We have no experience using our products for this indication although we have anecdotal reports that the anti-inflammatory benefits of our serum products help ameliorate post-inflammatory pigmentation responses. Hope this helps.

  29. Lisa says:

    What is your take is on topical alpha lipoic acid? It’s often touted as a powerful anti-inflammatory/antioxidant compound, so I would expect it to help prevent new pigmentation but not sure. Can you please share your thoughts on ALAs and best uses, if any?

    • drgeorge says:

      Darkened skin and spots occur when melanocytes are stimulated to produce melanin. Factors that stimulate melanogenesis include:
      • Ultraviolet (UV) radiation from the sun or tanning booths.
      • Hormones (from pregnancy, birth control, or conditions such as Cushing’s disease).
      • Chronic stress (leads to hormone imbalances).
      • Exposure to toxins or skin irritants, including from cosmetics, food poisoning, smoking tobacco, and PCBs.
      • Inflammation from injury, skin rash, or acne.
      Studies suggest alpha lipoic acid may indeed be a natural, safe skin lightener that can also even skin tone and reduce fine lines. It lightens skin by interfering with the pathways that cause hyperpigmentation. Alpha lipoic acid actions include:
       Anti-inflammatory effects.
       Antioxidant protection.
       Reduces expression of the key transcription factor protein that starts the skin pigmentation process.
       Decrease enzymes that promote melanin production.
      There have been some small clinical trials using alpha lipoic acid in combination with other ingredients or phototherapy for cosmetic improvement of skin. Results suggest that not only can alpha lipoic acid lighten dark spots; it may also help improve the appearance of aging skin.
      Selected excerpt from pertinent studies follow.
      Novel nanocapsule of α-lipoic acid reveals pigmentation improvement: α-Lipoic acid stimulates the proliferation and differentiation of keratinocyte in murine skin by topical application. Exp Dermatol. 2019 Feb;28
      Alpha-Lipoic acid has strong antioxidant effects and is used for the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as an antioxidant. Poor penetration limits its effectiveness when topically applied. Nano-encapsulation of α-lipoic acid improves skin permeability. Applied to murine (mouse) skin, epidermal thickening was observed which was confirmed to be due to the α-lipoic acid molecule. In in vivo experiments, it was found that it was very effective for improving UV-induced pigmentation and epidermal thickening.

      Effect of alpha lipoic acid on smoking-induced skin damage. Cutan Ocul Toxicol. 2017 Mar;36(1):67-73.
      OBJECTIVE:
      Skin exposure to cigarette smoke leads to the formation of reactive oxygen species and the generation of bioactive molecules that can damage skin cells. In rat skin exposed to cigarette smoke, degradation was observed in collagen bundles, hair follicles and sweat glands accompanied by mononuclear cell infiltration. When treated with alpha lipoic acid, all of these changes were improved. The study showed that cigarette smoke can cause degenerative effects on skin tissues in rats. However, ALA has a curative effect on cigarette-induced injuries on the skin tissues by anti-oxidative and anti-inflammatory effects.

      Evaluation of lipoic acid topical application on rat skin wound healing. Acta Cir Bras. 2013 Oct;28(10):708-15.
      The effects of lipoic acid (thioctic acid) topical application on surgical incision wound healing of rat skin was evaluated. Observations demonstrated improved wound healing with application of lipoic acid.

      The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle. Eur J Pharm Biopharm. 2014 Feb;86(2):251-9.
      Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects.

      Survey and mechanism of skin depigmenting and lightening agents. Phytother Res. 2006 Nov;20(11):921-34.
      Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Among the skin-lightening and depigmenting agents, magnesium-l-ascorbyl-2-phosphate (MAP), hydroxyanisole, N-acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-beta-d-glucopyranoside) and hydroquinone (HQ) are the most widely prescribed worldwide. However, with reports of potential mutagenicity and epidemics of ochronosis, there has been an increasing impetus to find alternative herbal and pharmaceutical depigmenting agents. A review of the literature reveals that numerous other depigmenting or skin-lightening agents are either in use or in investigational stages. Some of these, such as kojic, glycolic and azelaic acids, are well known to most dermatologists. Others have been discovered and reported in the literature more recently. Several depigmentation and lightening agents are discussed, including their historical background, biochemical characteristics, type of inhibition and activators from various sources. In addition, the clinical importance of mushroom tyrosinase as a recent prospect is discussed in this paper.

  30. iniyah williams says:

    I’m so happy I found this article and the physicians actually reply. I used a skin lightening cream called CaroWhite to lighten my bikini line and remove unwanted ingrown hairs; the product had hydroquinone in it. As a result of over using, I believe, my skin became darker! I have used literally everything.. I’ve exfoliated to the gods! nadolina, every cream, aloe vera, I’m afraid I now have ochronosis! Please help!

    • drgeorge says:

      Hydroquinone is banned, or limited to low concentrations, in many countries because of its purported role in carcinogenesis. It also is known to be associated with ochronisis.

      From Wikipedia:
      “Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. Macroscopically, though, the affected tissues appear bluish-grey because of a light-scattering phenomenon known as the Tyndall effect. The condition is most often associated with alkaptonuria, but can occur from exogenous administration of phenol complexes such as hydroquinone.”

      From Therapeutics in Dermatology:
      Treating ochronosis is not easy and treatment should mainly be preventive: it is essential to use low concentrations of hydroquinone combined with photoprotective measures and treatment should be discontinued if no improvement is observed after 6 months.
      Use of cryotherapy and trichloracetic acid has been found ineffective. Retinoic acid has been found to improve lesions, but not consistently.The use of mild dermocorticoids combined with photoprotective measures has been found to produce good results.
      Other treatments such as surgical peeling, CO2 laser resurfacing, glycolic acid peeling and Q-switched laser produce inconsistent and unpredictable results.

      I wish you had found us in time. We might have been able to prevent the issue while helping with your excessive pigmentation issues. We are very close to launching AnteAGE Brightener, a skin lightening product that incorporates our combinatorial approach of exploiting multiple pathways to lighten skin, without a molecule of hydroquinone in sight. Nary a one. Let us know what you do and how you progress. We care.

  31. sarah says:

    A year ago I had my underarms waxed and the lady waxed my skin off. It was red and swollen for the next 3 days and during that time I applied a skin healing cream called hexamide. It did help get rid of the swelling. After a couple of days, my skin started peeling off and it turned into a brown color. I limited sun exposure to the area so that it wouldn’t get darker and continued applying the cream until my underarms fully healed. Now almost a year later my underarms are a lot brighter but it still has a noticeable light brown pigment. I want to know if there is any way to get rid of the hyperpigmentation or is it too late?

    • drgeorge says:

      Hexamide is a combination of hexachlorophene and sulfanilamide to control microorganism growth. Preventing infection is prudent per se, but also helps manage the degree and duration of inflammation e.g. from infection, that would promote pigment production.

      The timing and degree of success in reducing inflammation has significant influence on pigmentation stimulation. A bigger issue is where the pigmentation occurs i.e. the epidermis or dermis. Dermal pigment is notoriously difficult to treat. There is no danger in using topical treatments, regardless of location of the pigment. Deeper pigment will be more resistant to treatment.

      Your hosts recently launched “Brightener” and “Brightening Microneedling Solution” products in our AnteAGE MD brand, and have a microneedling product available at our esthetician network for office treatments. Watch for a BFT post about the multi-pronged approach we used in these products. Neither contains hydroquinone. Seven pathways involved in pigmentation are addressed.

      The products contain ingredients that:
      1. Inhibit tyrosinase activity and co-factors
      2. Promote tyrosinase degradation
      3. Down regulate gene expression that promotes melanogenesis
      4. Inhibit the pro-melanogenetic effects of UV
      5. Inhibit melanosome transfer from melanocyte to keratinocyte
      6. Increase exfoliation of pigmented keratinocytes
      7. Counter the inflammation stimulus of UV and other stresses

  32. Casey says:

    After starting a new face regime some time ago, I noticed two nights ago that I have developed dark spots all over my face. I am 32 years old and have fair skin. My research revealed “if you notice freckles, brown spots, or a sunburn on your skin, you’re most likely not using a strong enough sunscreen. But if you notice pigmentation changes, particularly on your cheekbones, after applying a new product for a few days to a week, this can be a rare allergic reaction to certain ingredients usually used to lighten brown spots. Dermatologists call this paradoxical hyperpigmentation and it’s usually related to botanicals used to lighten the skin, such as kojic acid, arbutin, and hydroquinone. Discontinue all skin care containing these products and simply wait for the skin to balance itself out.”

    Honestly i was just looking to start some new skin care, and stop any aging and now all of a sudden this happened. Im looking at what i should do now to help this, I have not applied anything except vaseline last night and only have washed with water. Will this clear up on its own? Any helpful advice would be appreciated.

  33. DrGeorge says:

    People most prone to develop pigmentation in response to skin irritation (read “inflammation”) are those with higher Fitzpatrick number skin. For these people, it is especially perplexing and frustrating when products intended to reduce pigmentation actually do the opposite. You state you have fair skin so it is less likely for you although fair skin is notorious for forming “spots” of pigment. Red-headed people are well known to have freckles more often than other skin types. As a rule of thumb, the more prone one is to developing abnormal pigmentation, the more cautious one should be in using any product or treatment that has potential to inflame the skin. We’ll toot our horn here a little as we have learned that subduing the “basal” inflammatory state of the skin prior to any potentially inflammatory stimulus is the best way to keep hyperpigmentation at bay. The products we developed are used in many medical and esthetic practices as they have significant anti-inflammatory properties. Certainly, follow your skincare specialist’s suggestions as to how to cope with this annoying issue. Good luck. Let us know how it goes.

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