The pathogenetic role of UV radiation in phototoxic reactions and photoallergic dermatoses such as polymorphous light eruption (PMLE) has now become axiomatic. While sun-induced acute sunburn,melanomas, and nonmelanoma skin cancers (NMSC) are the primary concerns of people with Fitzpatrick skin Types I–III, the darker ethnic population ought to have effective sun protection as well, primarily for the prevention and management of photoallergic dermatoses and hyperpigmentation. Although the skin of color (SOC) is at a relatively less risk of developing skin cancers, it is not totally immune from them. The incidence of both melanoma and NMSCs is approximately 5% in Hispanics, 4% in Asians, and 2% in blacks.[1]  In people with SOC, both basal cell skin cancers and squamous cell carcinomas    may arise, with the former being the most common form of   skin cancer associated with SOC.[2] Of late, the pathogenetic role of UV radiation on accelerating premature graying of hair has also been recognized.[3] In essence, one needs effective sunscreens for sun protection on a daily basis. However, the acceptability and compliance with the use of topical sunscreens depend on various factors Although broad spectrum topical sunscreens constitute the most important component of sun protection, they have many limitations that culminate into noncompliance or sub-optimal use. Even in populations  at high  risk of   UV-induced skin cancers, dherence with sunscreen application has been reported low despite the awareness of  the    benefits of sunscreen.[4]

Limitations of Topical Sunscreens

In order to achieve the labeled sun protection factor (SPF), a uniform application of 2 mg/cm2 sunscreen is recommended, for which at least one teaspoon (around 3 ml) of preparation should be applied on the face, neck, and nape.   However, in reality, most patients apply much lesser   amounts, resulting in sub-optimal application thickness, as reported in  a recent study.[5] A sunscreen should ideally be applied at least 30 min prior to anticipated exposure. In practical experience, it is   often not feasible for busy professionals. Moreover, reapplication every 2–3 h, after swimming, excessive sweating, etc.,  becomes a strong barrier to compliance. The cosmetic   acceptability of the sunscreen is also important, especially for   women. The opaque nature and “whitening effect” of physical sunscreens containing zinc oxide (ZnO) and/or titanium dioxide   (TiO) are an inherent disadvantage which has now been minimized by the use of nanosized particles (NP) (size 1–100 nm). However, in recent years, there have been     concerns about the possibility of NP penetrating the stratum   corneum with resultant genotoxicity. Despite many studies establishing the safety of TiO and ZnO NP, skepticism about the possibility of genotoxicity by NP-grade TiO continues to simmer.[6]

Further on, photoallergic reactions are fairly   common with topical sunscreens. The demands of having positive attributes in a including high SPF, easy spreadability, high substantivity, sweat and water resistance, nonoily feel, photostability, cosmetic acceptability, etc., have led to the development   of complex sunscreen products with very long ingredient   lists in terms of both active agents and excipients, increasing their allergenic potential.[7] Last but not least, a topical sunscreen will provide UV protection only over the areas where it is applied over, that is, it is devoid of “systemic sun protection.” Patients frequently need to use huge amounts of sunscreen during beach exposure to prevent tanning.

Advantages of “Systemic Sunscreens”

The above-mentioned reasons have led to the topical sunscreen often being used inadequately or improperly. An “ideal” oral sunscreen which would be as effective as a topical sunscreen say, with an SPF of 30 or more would have several advantages, with convenience and ease of use topping the list. Patients would find it much easier to pop-in a pill and rather than applying the topical sunscreen every 2–3 h. The performance of oral sunscreens would not be affected by external conditions, such as  swimming, types of  garment, or  sweating.  Most importantly, an effective oral sunscreen will provide protection to the entire body, including the trunk, lower limbs, as   well as scalp, and hair. Until now, compounds with strong anti-oxidant   potential including Vitamins  C  and  E,  polyphenols, carotenoids,

lycopene, flavonoids, proanthocyanidin, and other anti-oxidants have been prescribed to provide only ancillary sun protection over and above the topical sunscreens.[8] The latest in this league is a specific fern extract called Polypodium leucotomos (PL), which seems to be effective to a certain extent in   providing photoprotection, when taken orally.

Polypodium leucotomos: The Latest Oral Sunscreen on the Block

PL or anapsos, a synonym, is a South American species of fern in the family Polypodiaceae. Extant research has shown that extracts of PL possess robust anti-oxidant,  photoprotectant, antimutagenic,  and  immunoregulatory  properties.[9] The extracts of PL applied topically or taken orally have been shown to  be  effective in  several dermatoses in   research conducted over the last four decades, such as psoriasis   and vitiligo. Since then, a variety of other dermatoses  including atopic dermatitis, and more importantly,    photo-responsive dermatoses such as  PMLE, solar urticaria, and    melisma, have been reported to improve with intake of this fern’s extracts.[9]   PL is a natural mixture of phytochemicals     with powerful  anti-oxidant  and  photoprotective properties, including  acids  such  as  ferulic,  caffeic, vanillic,p-coumaric,  3,4-  dihydroxybenzoic, 4-hydroxybenzoic, hydroxycinnamic,  4-hydroxycinnamoyl-quinic, and chlorogenic. The versatility of its use stems from its pleiotropic effects. The evidence favoring the UV protective effect of oral PL is growing. Its mechanisms of effect include:

1.           Anti-oxidant activity: The anti-oxidant activity of PL results in the control of cutaneous responses to UV-induced erythema.[9] UV-induced erythema and skin damage are primarily a result of reactive oxygen species (ROS) produced at the cellular level. PL inhibits the generation of ROS at a molecular and cellular level to enhance endogenous anti-oxidant systems

2.           Photo prevention: The photoprotective effect of PL stems from a concerted anti-oxidant, anti-angiogenetic, and extracellular matrix remodeling effects.[9,10] PL inhibits UV-mediated oxidative DNA mutations, prevents photodecomposition of both endogenous photoprotective molecules and DNA, and enhances DNA repair. Acting at a cellular level, PL acts at the cellular level, improving cell membrane integrity and elastin expression, resulting in prevention and repair of solar damage

3.           Cancer prevention: PL has also been shown to increase epidermal p53 expression and accelerate the  removal  of UV-induced photoproducts, highlighting its anti-carcinogenic role.[11]

Modern studies involving animal models, in vivo human skin cell cultures and human volunteers have evaluated the efficacy of polymorphic light eruption (PLE) orally as a photoprotective agent and for use in several photo-aggravated dermatologic disorders, melisma, and vitiligo.

Evidence Favoring Photoprotective Properties of Polypodium leucotomos

After initial encouraging results from mice-based studies, Alonso-Lebrero et al. determined the effects of PL in the presence of UVA or UVB radiation on markers of solar elastosis, collagen reduction, and increased expression  of matrix metalloproteinases (MMPs). Fibroblasts and keratinocytes, respectively, were irradiated by a single exposure to UVA or UVB radiation, and then incubated with or without PL. PL significantly improved membrane integrity, inhibited lipid peroxidation, increased elastin  expression, and inhibited MMP-1 expression in both fibroblasts, and keratinocytes, in the presence of UVA as well as UVB.[10]      In one of the pioneer studies conducted by González et al., 21 healthy volunteers were exposed to solar radiation with oral psoralens and immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose, and minimal phototoxic dose (MPD) were evaluated, before and after topical or oral administration of PL. PL significantly increased UV dose required for IPD, MED as well as MPD, both after topical and oral administration.[12]    In a randomized, double-blind, placebo-controlled human volunteer study conducted by Nestor et al., oral PL (240 mg.) was administered twice daily to 10 healthy adults, aged 18–65 years with Fitzpatrick skin Types I–IV for 60 days. The subjects in the treatment group showed a lesser likelihood of experiencing ≥1 episodes of sunburn, increased MED,    and decreased UV-induced erythema intensity; all results   being statistically significant. There were no changes in any safety assessment parameters.[9]

Efficacy of Polypodium leucotomos in Vitiligo: Enhancing Repigmentation,Decreasing Phototoxicity

Recent trials have  confirmed that  when   phototherapy is  delivered with PL,  there is  a  definite enhancement   of efficacy. A randomized,  double-blind,  placebo-controlled pilot study of patients with generalized vitiligo (n = 19) and healthy controls (n = 19), that compared the    combined efficacy of psoralen plus ultraviolet A (PUVA) plus oral  PL versus PUVA plus placebo, reported a significantly     higher percentage of patients with > 50% skin repigmentation among patients who received PL.[13]   In another randomized     study with generalized vitiligo (n = 57), combination therapy with twice weekly narrow-band (NB)-UVB and once daily PL 480 mg resulted in 40% re-pigmentation, compared to   22%for NB-UVB phototherapy alone.[14]  Middelkamp-Hup et al. conducted two separate studies to assess the efficacy of   PL as an effective chemophotoprotector against  PUVA-induced skin phototoxicity.[15,16]   Healthy participants (n = 19)     with skin phototypes II to III were exposed to UVA alone (n =  9) or with 0.6 mg/kg oral 8-methoxypsoralen (n = 10),  without and after administration of 7.5 mg/kg of oral PL.  Clinically, a significant decrease in erythema was found in   PL-treated skin after 48–72 h. Histologically, PLE-treated skin revealed cellular changes that confirmed the chemoprotective effect of PLE against PUVA-induced skin phototoxicity.

Efficacy of Polypodium leucotomos in Melasma

The beneficial effects of  PL in  melasma need    further elucidation. One recent study demonstrated the clinical efficacy of PL in melasma. Female subjects (n = 21; aged 18–50 years) with epidermal melasma (n = 21) were randomized to receive oral PL or placebo twice daily for 12 weeks, with additional application of a sunscreen (SPF-45) daily. At 12 weeks, patients who are treated with PL showed significantly decreased mean Melasma  area  and  severity  index  (MASI)  scores whereas the placebo group did not.[17]   However, contrary     findings were observed in  another randomized,   double-blinded, placebo-controlled trial conducted in 33 Hispanic women with moderate to severe facial melasma.[18] They were randomized to receive either 240 mg oral PL or placebo, 3 times daily for 12 weeks. All subjects were given a standard, broad spectrum, and  topical sunscreen to  use  every morning. While   both groups showed significant improvement in melanin index and MASI at week 12, the intergroup difference was statistically insignificant.

Safety

In nearly all studies mentioned above, no significant adverse effects were reported in the PL groups. In a status  report on clinical efficacy and safety of PL based on data interpreted from 19 human and 6 basic science studies spanning over 40 years of research, they concluded that PL is well-tolerated    at all doses administered (120–1080 mg/day) and  associated with a negligible risk of side effects. While laboratory studies did not report any adverse effect; mild to moderate astrointestinal complaints and pruritus were reported only in     2% human cases (16/1016).[19]   No significant drug  interactions have been reported. However, data on long-term and safety in children, pregnant and lactating women are lacking. Notably,commercial capsules of PL are not free from gluten so should not be consumed by gluten-sensitive people.

Commercial Availability of Polypodium leucotomos

Globally,  PL capsules are  most commonly available under the category of “health supplement,” under    various brand names. Specific brands are popular in  different countries.The commercially available PL containing capsules typically contain 240 mg of the extract of PL; and   often additionally contain Vitamins C and E and lycopene. As per   the general recommendations of leading manufacturers of this compound:

1.           The  capsules should be  consumed 30  min  before sun exposure

2.           On a day with regular sun exposure, 2 capsules should be taken per day (1 in the morning and 1 in the midday). On a day for intense sun exposure, 4 capsules should be taken (2 in the morning and 2 in the midday, that is, 3 h after first dose)

3.           Recommended duration of therapy: The capsules should be taken “daily (indefinitely) to provide continuous adjuvant sun protection.”

Controversies about Polypodium leucotomos

The biggest dilemma about the practical utility of PL capsules as “oral sunscreen” stems from the following factors:

1.           There are no published studies to date that directly compare oral PL supplements to topical sunscreens. Moreover, oral sunscreens cannot be labeled with an SPF. González, one of the pioneer researchers of PL, has suggested that this drug offers an SPF of about 3–5; insufficient (if used alone) for most people that need sunscreen[20]

2.           Data about absorption of PL extracts and how much of the absorbed drug reaches the skin to provide photoprotection are not available

3.           The dose and schedule have not been precisely specified for any indication. The doses used in trials   for different indications have generally ranged from 240 mg    to 480 mg/day. The basis of the manufacturer’s recommendations of the dosages (vide supra) are based upon these  limited number of trials. The studies conducted in healthy volunteers suffered from one or more of the following flaws: Modest sample size, lack of control group in some studies, no rationale for the dose used, lack of blinding, lack of evaluation of long-term effects, and use of UVA sensitizers to enhance UVA damage which cannot be extrapolated to its usefulness in real life sun protection from regular or intermittent sun exposure

Conclusion

Although the idea of a well-tolerated, safe, oral supplement that protects against UVA and UVB without the need for   topical products is an attractive one, we need more evidence to confirm the efficacy and safety of PL fulfilling these criteria. At present, the quality of evidence in favor of PL for any particular condition is not robust. The studies mentioned above, of course, cannot be ignored, and considering their positive outcomes, PL seems to be effective in reducing some of the severity of sunburn, and may provide some UV protection in photodermatoses and patients undergoing phototherapy. Its role in pigmentation  reduction and anti-aging remains unclear. It is clear that PL cannot be an alternative, but only an adjuvant to topical sunscreens. Its current evidence-based clinical utility seems to lie in a mild adjuvant role to topical sunscreens, prevention of sunburns in fair-skinned people, and possibly in vitiligo to enhance repigmentation and reduce phototoxicity of UVA or UVB therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.     Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol 2006;55:741-60.

2.     Agbai ON, Buster K, Sanchez M, Hernandez C, Kundu  RV, Chiu M, et al. Skin cancer and photoprotection in people  of color: A review and recommendations for physicians and the public. J Am Acad Dermatol 2014;70:748-62.

3.     Pandhi D, Khanna D. Premature graying of hair. Indian J Dermatol Venereol Leprol 2013;79:641-53.

4.     Pissavini M, Doucet O, Diffey B. A novel proposal for labelling sunscreens based on compliance and performance. Int J Cosmet Sci 2013;35:510-4.

5.     Novick R, Anderson G, Miller E, Allgeier D, Unice K. Factors that influence sunscreen application thickness and potential reservative  exposure.  Photodermatol Photoimmunol Photomed 2015;31:212-23.

6.     Nohynek GJ, Dufour EK. Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: A risk to human health? Arch Toxicol 2012;86:1063-75.

7.                  Saraswat A. Contact allergy to topical    corticosteroids and sunscreens. Indian J Dermatol Venereol Leprol 2012;78:552-9.

8.                  Skotarczak  K,  Osmola-Mankowska  A, Lodyga M, Polanska  A, Mazur M, Adamski Z.  Photoprotection: Facts and controversies. Eur Rev Med Pharmacol Sci 2015;19:98-112.

9.                  Nestor MS, Berman B, Swenson N. Safety and efficacy of oral Polypodium leucotomos extract in healthy adult subjects. J Clin Aesthet Dermatol 2015;8:19-23.

10.             Alonso-Lebrero  JL,  Domínguez-Jiménez  C, Tejedor R, Brieva A, Pivel JP. Photoprotective properties of a hydrophilic extract of the fern Polypodium leucotomos on human skin cells.J Photochem Photobiol B 2003;70:31-7.

11.             Rodríguez-Yanes E, Cuevas J, González S, Mallol J. Oral administration of Polypodium leucotomos delays   skin tumor development and  increases  epidermal  p53 expression and the anti-oxidant status of UV-irradiated hairless   mice. Exp Dermatol 2014;23:526-8.

12.             González  S,  Pathak  MA,  Cuevas  J,  Villarrubia VG, Fitzpatrick TB. Topical or oral administration with an extract  of  Polypodium leucotomos prevents  acute sunburn and  psoralen-induced phototoxic reactions as   well as depletion of Langerhans cells in human skin. Photodermatol Photoimmunol Photomed 1997;13:50-60.

13.             Reyes E, Jaén P, de las Heras E, Carrión F,  Alvarez-Mon M, de Eusebio E, et al. Systemic     immunomodulatory effects of Polypodium leucotomos as an adjuvant to    PUVA therapy in generalized vitiligo:  A  pilot  study.  J  Dermatol  Sci 2006;41:213-6. 25

14.             Middelkamp-Hup MA, Bos  JD,  Rius-Diaz  F,  Gonzalez S, Westerhof W. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract:  A randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol 2007;21:942-50.

15.             Middelkamp-Hup  MA,  Pathak  MA,  Parrado  C, Garcia-Caballero T, Rius-Díaz F, Fitzpatrick TB, et al. Orally administered  Polypodium  leucotomos extract decreases psoralen-UVA-induced  phototoxicity,  pigmentation,  and damage of human skin. J Am Acad Dermatol 2004;50:41-9.

16.             Middelkamp-Hup MA, Pathak MA, Parrado C, Goukassian D, Rius-Díaz F, Mihm MC, et al. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.J Am Acad Dermatol 2004;51:910-8.

17.             Martin LK, Caperton C, Woolery-lloyd H.   A Randomized Double-Blind Placebo  Controlled  Study Evaluating the Effectiveness and Tolerability of Oral Polypodium leucotomos in Patients with Melasma. Presented at: American Academyof  Dermatology  Annual  Meeting. San Diego, California;March  16-20,  2012.  Available from: https://www.clinicaltrials.gov/ct2/show/NCT01162850. [Last accessed on 2015 Mar 26].

18.             Ahmed AM, Lopez I, Perese F, Vasquez R, Hynan LS, Chong B, et al. A randomized, double-blinded, placebo-controlled trial of oral Polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. JAMA Dermatol 2013;149:981-3.

19.            Winkelmann RR, Del Rosso J, Rigel DS. Polypodium leucotomos extract: A status report on clinical efficacy and safety. J Drugs Dermatol 2015;14:254-61.

20.             Woolston C.  Does heliocare combat the  sun’s   rays? Los Angeles Times; June 1,  2009. Available    from: http://www.latimes.com/health/la-he-skeptic1-2009jun01-story.html. [Last accessed on 2015 Apr 17].

This is what I read on the internet some other day. Today this applies to men as well as women as both seem to have been bitten by “look your best” bug. Ageing and fat (specially the sudden loss of fat), are responsible for sagging skin. Gravity and pregnancy also contribute to further sagging of the skin.

Wrinkles, jowls and double chin are the consequences of facial skin sagging and extra folds of skin at the elbows, knees, abdominal overhanging (on all sides) and sagging breast are contributed by ageing of the body skin.

Reduction in elastin, collagen and glycose amino glycans of the skin contribute to genetically programmed ageing of the skin. These effects are enhanced by extrinsic factors such as UV radiation, temperature variation ( I think AC is the biggest culprit), gravity, wind or excess humidity, pollution, vices (drinking & smoking), poor nutrition and mental stress (that we doctors have in abundance). Hence we are left with a loose, wrinkly and dry skin in the respective order as we marinate….oops! I mean mature (that’s a graceful word we have found for ageing!). Pigmentary alterations also do occur as an ageing process but it is out of the scope of this article.

While a host of surgical and non surgical procedures are available for skin lifting, the choice of treatment actually depends upon the extent of damage done. While filler treatment is reserved for early sagging and surgical resection for pretty advanced stage, moderate amount of sagging of the skin is the ideal stage for introduction of PDO threads in the skin.

Polydioxanone (PDO) filament is a synthetic absorbable suture which is prepared from polyester, poly(p-dioxanone). PDO is a colourless, crystalline, bio-absorbable polymer that was developed specifically for wound-closure sutures. As a suture, it exhibits high flexibility, higher retention strength, slower-absorption rate and lower-inflammatory response rate when compared to Vicryl (poly(glycolic-co-lactic acid)) and Dexon (poly(glycolic acid)). PDO is non-antigenic in nature. It carries no risk of bacterial colonization/ infection. The monofilament suture typically loses 50% of its initial breaking strength after 3 weeks and is completely absorbed within 6 months, making it most suitable for tissue engineering rather than wound closure [17,18]. These characteristics of PDO enable it to stimulate production of collagen and fibroblasts in response to its implantation. Thus PDO brings about skin tightening and scar resurfacing. PDO also increases the blood flow around the threaded areas, which result in skin rejuvenation.

PDO is degraded by hydrolysis, and the end products are mainly excreted in urine.

Packaging

PDO threads are generally available in a pack of 10 needles. The thread is pre-inserted into the needle (21 G) in the 80:20 ratio, that is 80% inside the needle and 20% outside the needle. The needle tip is specially developed with a back cut-end to prevent direct trauma to the blood vessels and other delicate structures reducing the chances of haematoma along the thread length. There are different types of PDO threads available for a variety of indications and various sizes such as 30mm, 50mm, 60 or 70mm and 90 mm to fit and satisfy the dimensions of various body parts. The first two lengths or sometimes even higher lengths are used for face while bigger lengths are used for body for obvious reasons.

MECHANISM OF ACTION OF THREAD LIFT

The entire basis of the thread-lift technique is the foreign body cutaneous response to the presence of PDO threads within the skin.

Pre-procedure counselling and preparing the patient

A detailed consultation, pre-treatment photographs in various positions informed written consent are all carried out prior to the procedure. Detailed history regarding any other medical complaints should be recorded. Blood pressure and sugar levels should be documented.  Due precaution and prudence should be exercised in case the patient is suffering from any medical illness. Patients using anti-coagulants should be advised to stop using them at least 10 days before the procedure, only after being permitted by their treating physician.

Procedure

A topical anaesthetic cream is applied 30 mins–1 hour before the procedure. The procedure could be carried out in a medical office or in a day surgery. Rigorous sterility measures should be undertaken. The skin should be stretched by the surgeon’s left hand (for a right-handed surgeon) to make it taut. The right hand of the surgeon pierces the skin with the needle tip. While piercing the skin with the needle tip, the needle should be kept as parallel to the skin as possible. After a give way feeling, the needle should be glided straight inside the skin. A vigilant eye should always be kept on the needle tip through the skin to reduce the chances of damaging internal structures. The entire length of the needle should be inserted till the hub of the needle touches the skin.

Few more such needles should be inserted parallel to the first needle in a given area before withdrawing any of the inserted needles. This helps as a reference for the next needle. It also reduces the time for the procedure.

These needles should, however, be removed before inserting the perpendicular needles to form a mesh of threads to prevent damage to the skin. The inserted needles are swiftly removed one by one. Even while removing other needles, firm pressure with a gauze piece should be maintained on the site of already withdrawn needles. Firm pressure should be maintained for around 10 mins to achieve good haemostasis. The same procedure is repeated in a perpendicular direction to create a mesh for significant neo-collagenesis.

The number of threads required depends upon the indication trying to use as many as possible. A face generally needs 50 to 60 threads for a great results and additional 20 to 30 threads for neck.

An antibiotic and anti-inflammatory therapy is required for 10 days. It is very important to not to stress the operated area by restricting the muscle movement underneath.Patient may resume a moderate physical activity 25 days after and a more intense activity such as swimming 45 days after the procedure. In case any other body part is treated, movement should be restricted for a couple of days accordingly.

Results

The positive benefits of this treatment appear in two phases. As a part of the early changes, rejuvenation effects are noticed after 1 or 2 months. The complexion improves and pigmentation reduces. By 3 months-time, patients experience up to 40% of tissue tightening which is manifested as slight blunting of the static wrinkles or shallowing of the scars The increment of naturally-produced hyaluronic acid, collagen and elastin and the fibrosis induced by the particular and specific shape of the threads starts optimizing the results by 6-months duration. One sitting may lead to 80% improvement in the concern for which the treatment is done. Additional improvement can be aimed by undergoing another thread-lift procedure as early as 2 months after the initial treatment.

Complications are minimal and restricted to infection, haematoma, peeping threads or inflammatory papules at insertion sites. Peeping threads should be cut and mild steroid settles the papules.

Thread lift, according to me, is a great and simple tool in our hand to achieve gratifying results…..and thank God that the 10 mins dryer thing doesn’t work for our skin!

PN: For additional information on thread lift, please refer to Chapter 15 Non-Surgical Facelift authored by me in the upcoming book, Cosmetic Dermatology, A practical and Evidence-based Approach.