Cysteamine Cream (Cyspera) for Hyperpigmentation

During the last several years, dermatologists have been increasingly prescribing cysteamine cream to treat melasma and other hyperpigmentation conditions. The most well known brand is Cyspera, which Dr. Corey Hartman really likes. He states that it is his:

First choice for patients dealing with hyperpigmentation, especially patients of color.”

In February 2022, Practice Update concluded that stabilized topical cysteamine can be considered a first-line non-hydroquinone option for patients with various hyperpigmentation related conditions. This includes melasma, postinflammatory hyperpigmentation, lentigines, and dyschromia related to facial aging.


Cysteamine (not to be confused with cystamine) is a naturally occurring amino acid (via cysteine or cystine) in the human body.

Since Cysteamine is a natural antioxidant compound, it usually results in no major long-term side effects in skin. In contrast, the gold standard popular hydroquinone treatment can cause permanent skin damage, especially in people of color.

One 2020 case report found that topical Cysteamine 5% cream significantly improved a person’s chronic postinflammatory hyperpigmentation (PIH). Moreover, this patient with skin type 5 saw no results from using a popular triple combination cream (containing hydroquinone, topical corticosteroids, and retinoids). The skin lightening effect was noted by a reduction in the melanin index.

A 2014 study from Iran found Cysteamine 5% cream to show significant efficacy in the treatment of melasma.


Cyspera cream with Cysteamine
Cyspera cream with Cysteamine.

The main product that is currently available on the market is Cyspera pigment correction cream. The manufacturer Scientis Pharma (Switzerland) has an Instagram page with some good before and after photos. They sell the product in a three can combo called The Cyspera Intensive System™. It costs $285 on their website, but is not currently sold on Amazon. The system consists of:

  • Cyspera Intensive™ (30 ml / 1 fl oz).
  • Cyspera Neutralize™ (50 ml / 1.75 fl oz).
  • Cyspera Boost™ (30 ml / 1 fl oz).

The main ingredient is referred to as Cysteamine Isobionic-Amide Complex™.

Dr. Alexis Stephens has a useful video covering this cream. Board certified dermatologist Dr. Dray (Andrea Suarez) reviewed Cyspera in an unbiased manner in 2020. American Academy of Dermatology President Dr. Seemal Desai is a fan of this product.

Also see the below video from Dr. Sheila Nazarian at the Skin Spot:

It used to be too difficult to compound a 5% cysteamine based topical cream that was stable, but Cyspera managed to overcome this challenge. One minor issue with this product is its strong rotten egg (sulfur) smell according to some reviewers.

How Does it Work?

According to Dermnetz, Cysteamine cream works via the following hypothesized mechanisms:

  • The inhibition of tyrosinase and peroxidase.
  • Scavenging of dopaquinone.
  • Chelation of iron and copper ions.
  • Increase of intracellular glutathione.

How do you Apply Cysteamine Cream?

According to Dr. Nazarian, during the first 16 weeks, you will need to apply the cream once per day. Thereafter, during the maintenance phase, you will just need to apply it two times a week.

Other Cysteamine Based Creams

A number of other companies seem to be selling cysteamine based creams. I will try to update this post as I find more that seem legitimate.

US based Senté makes a Cysteamine based pigment and tone corrector cream. It also includes a patented Heparan Sulfate Analog (HSA). The cream evens out complexion in all skin tones and improves the appearance of dark spots. Moreover, it is hydroquinone-free and safe for long-term use in those with sensitive skin. The cost of one tube is pretty significant at $149.

Note that Cysteamine is not a photosensitizer. This means that it can be applied at any time of the year, regardless of sun intensity.

Dermatosis Papulosa Nigra Removal

Dermatosis Papulosa Nigra (DPN) are common in people with dark skin, especially in African Americans. Perhaps the most famous person with these mole like protuberances on his face is actor Morgan Freeman. DPNs tend to appear on the face, neck and upper torso regions most frequently.

DPN Overview

DPN lesions generally emerge during puberty and usually have a genetic hereditary propensity (similar to seborrheic keratoses). They typically occurs in individuals with Fitzpatrick skin types III to VI. Therefore, people of South Asian and African heritage tend to have higher occurrence rates of Dermatosis Papulosa Nigra. Women are also more likely to have Dermatosis Papulosa Nigra.

DPN is considered to be a common variant of seborrheic keratoses (SKs). It was first described in 1925 by Dr. Aldo Castellani, based on his observations while visiting Jamaica and Central America. DPN papules (bumps) appear as 1 to 4 mm brown or black dots that resemble moles. They tend to increasing steadily in number and size as a person ages, with spontaneous regression highly unlikely. The DPN marks are almost always benign and noncancerous, with no treatment required. However, people may wish to remove them if they find them to be cosmetically undesirable.

One study found that people with darker skin who used skin lightening creams tended to have a larger number of DPN bumps. This could be due to reduced UV ray protection from the loss of protective skin pigment melanocytes.

Dermatosis Papulosa Nigra Removal

Dermatosis Papulosa Nigra Removal
Dermatosis Papulosa Nigra (DPN) removal from face using a pulsed dye laser. Source: Indian Journal of Dermatology.

DPN removal options include the following surgical and non-surgical methods:

  • Scissor excision via snipping.
  • Cryotherapy. Liquid nitrogen is generally used to freeze off the bumps. However, in people with darker skin, cryotherapy can cause hypopigmenation or hyperpigmentation due to potential damage of melanocyte cells.
  • Curettage. A dermatologist will scrape off the bumps with a small surgical instrument.
  • Electrocautery. An electric current runs through a small probe with a fine needle electrode tip. This current burns (cauterizes) the DPN skin tissue, but does not pass through the patient’s body.
  • Electrodesiccation. A professional will zap the bumps with a low electric current using a probe. Topical anesthesia is usually applied before this treatment. This procedure (also called fulguration) uses heat from the electric current to pass through and destroy the abnormal DPN tissue.
  • Laser Therapy. Among lasers that have been used to successfully remove Dermatosis Papulosa Nigra in patients include: potassium titanyl phosphate (KTP) lasers; pulsed dye lasers (PDL); Nd:YAG lasers; Q-switched and picosecond lasers; and CO2 lasers. In general, the Nd:YAG 1064 nm wavelength lasers are the most suitable for people with dark skin. However, talk to your dermatologist to see which is best for your type of skin.

Scarring, dyspigmentation, skin discoloration, greying, crusting, and keloid formation are potential complications that can arise after Dermatosis Papulosa Nigra removal. Note that DPN lesions can always recur after treatment with any of the above modalities.


DPN versus Seborrheic Keratoses

Dermatosis Papulosa Nigra (DPN) is considered to be a common variant of seborrheic keratoses (SKs). However, a recent report denoted some major differences between the two.

  • While DPN affects darker skin types, SKs are far more common in lighter-pigmented individuals with Fitzpatrick skin type I to II.
  • DPN lesions are largely limited to sun-exposed areas of the body (face and neck). In contrast, SKs have a more widespread distribution.
  • Morphologically, DPN lesions are relatively small and uniform. SKs on the other hand vary widely in size and shape. Some seborrheic keratosis diameters can reach several centimeters in size.
  • While DPN and SKs genetically share a common somatic activating mutation (FGFR3), DPN lacks the mutation in PIK3CA that is found in SKs.

Post Treatment Care

After treatment, one must take a number of precautions. Sun exposure should be kept at a minimum, and always after application of sunscreen. Do not pick at your lesions and treated areas, even if their is significant itching. Try not to use any kinds of creams, makeup, acid containing products or other potentially harmful lotions with chemical ingredients.

Tranexamic Acid for Skin Lightening and Melasma

In recent years, Tranexamic Acid (TXA) has become increasingly popular for skin lightening and treating conditions such as melasma and dark spots. Tranexamic acid is a tyrosinase inhibitor and has anti-inflammatory properties that can even out skin tone. Note that TXA has not been officially licensed for use in dermatological conditions, so it is used off-label for skin applications.

Historically, tranexamic acid has been used to treat excessive blood loss (from surgery, postpartum bleeding, heavy menstruation and more) due to its blood clotting properties.

How does Tranexamic Acid Work?

According to DermNet NZ, the mechanism of action of tranexamic acid involves the shrinkage of dermal vasculature and reduced melanin synthesis. The latter is achieved via altering the interaction of keratinocytes and melanocytes, and via reduced tyrosinase activity. There are a number other products that reduce hyperpigmentation via tyrosinase inhibition.

Most topical products that contain tranexamic acid use 2% to 5% formulations. The oral dose used to treat melasma is 250 mg twice per day. A 2021 study found that a new topical tranexamic acid derivative improved overall facial skin tone and reduced the appearance of dark spots and redness.

Topical Skin Serums and Lotions

Tranexamic Acid Serum
Tranexamic acid 5% serum from Dearskin.

There a number of popular commercial lotions and serums that contain tranexamic acid. Among the most popular ones on Amazon is a 5% Tranex serum from Dearskin. It has an average rating of 4.3 out of 5 stars based on almost 1,000 reviews as of today. It is currently on sale for just $15 after a coupon discount.

Besides containing TXA, this product also includes other proven skin lightening and brightening ingredients such as kojic acid, niacinamide, vitamin C, hyaluronic acid and glycolic acid. Tranex has been tested by dermatologists and is cruelty free and vegan (not tested on animals). It is also formaldehyde- and paraben-free, and is made in the USA.

Another recommended product is The INKEY List’s tranexamic acid 2% hyperpigmentation treatment gel. The low concentration makes this a good option to start experimenting with TXA. It also contains acai berry extract and Vitamin C.

Using Tranexamic Acid in Skin of Color

Dr. Rattan has a great video titled: “Is Tranexamic Acid Suitable For Skin Of Color”. She is a fan of this ingredient since it is skin neutral. It works best on pH 5-7, which is approximately the same pH level as our skin. Dr. Rattan prefer to use tranexamic acid in combination cocktail products rather than via monotherapy, especially for stubborn melasma conditions.

Potential Side Effects

In general, Tranexamic acid is safe and well-tolerated by all skin types (assuming you use a reputable product and low dosage). Mild side effects include skin irritation, scaling or flaking, dryness and erythema. Most of these can be reduced with the use of moisturizer creams. Moreover, note that TXA can also reduce post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH) due to its anti-inflammatory effect.