Authors: Dr. Brijesh Nair

Hope the first part of this series must have acted as a ‘noodle – nudger’ for those little grey cells of practising dermatologists and aestheticians.So here is a second serving of the heady cocktail called (EBM)2 – Evidence based medicine and Experience based medicine, which should hopefully embellish your practice. So here goes.

1. We practitioners are familiar with the ophthalmological drug called Bimatoprost, a prostamideanalogue which has been found to enhance eyelash length and has found its niche in trichology and pigmentary dermatology in treatment of alopecia areata and vitiligo respectively.It’s history has been marked by a series of serendipities.
Prostaglandin analogs have been used by ophthalmologists for management of glaucoma. The lengthening of the eyelashes was an incidental finding observed by eye specialists which translated into a block-buster preparation (FDA approved in 2008). This drug has been marketed as Latisse, by Allergan and generics are available in Indian market.
The purported mechanism for induction of hypertrichosis seems to be binding to prostaglandin receptors on hair follicles and increasing the percentage of hairs in anagen phase, increasing the duration of anagen phase, decreasing the duration of telogen phase, increasing the size and thickness of the dermal papilla (hair bulb), and stimulating pigment cells in hair follicles and skin. But what caught my ‘eye’ were the purported changes in the appearance of the periorbital area, beyond eyelash enhancementas mentioned by an article (Journal of Drugs in Dermatology 2015; 14(5): 472-77.)
An optometry journal initially reported that three patients treated with unilateral bimatoprost developed ipsilateral deepening of the upper eyelid sulcus and involution ofblepharochalasis, which reversed on treatment cessation (Optom Vis Sci.2004; 81:574-577.).The findings were recapitulated in another study which showedsimilar changesafter bimatoprost use in glaucoma.(OphthalPlastReconstr Surg. 2008; 24:302-307).This led to description of a new entity Prostaglandin Associated Periorbitopathy(PAP) the criteria for which includes-

1. upper eyelid ptosis,
2. deepening of the upper eyelid sulcus,
3. involution of dermatochalasis,
4. periorbital fat atrophy,
5. mild enophthalmos,
6. inferior scleral show,
7. increased prominence of eyelid vessels, and

8) tight eyelids.Other changes were lengthening and darkening of the eyelashes,hyperpigmentation of the periorbital skin, or changes in the color of the iris (Glaucoma Today. 2011; 9(3):51-52,58.) .
The PGF2α or PGA molecule binds to the prostaglandin F2 alpha receptor (FP receptor) on preadipocytes. A complex series of reactions is initiated that results in inhibition of adipocyte differentiation and a decrease in fat accumulation within adipocytes; this eventuates in fat atrophy (Endocrinology. 1995;136:3222-3229.),
which can explain the changes. In some individuals, however, these findings may, in fact, be beneficial to the cosmetic appearance. The periocular changes fortuitously created, can simulate a blepharoplasty. These kind of changes were reported even on eyelash application of bimatoprost for aesthetic purposes. In many cases the treated eye appears more youthful – with more pretarsal show, resolution of dermatochalasis, and reduction of pseudoherniated periorbital fat.
One downside is variability in time of onset of PAP, with difference between two eyes! The clinical features of PAP are reversible – either partially or fully – with discontinuation of treatment, which is encouraging.Bimatoprost showed the greatest inhibition of adipogenesis among prostaglandin analogs. Significant periorbital absorption of Prostaglandin analogs (PGAs) is proven and hence even eyelash use induces these changes. (J PharmacolExpTher. 2003;305:772-785.).
Aestheticians can try to harnessbimatoprost by choosing appropriate candidates and must use the drug bilaterally.PGAs can make the eyes appear larger. The potential disadvantages of bimatoprost include the risk for hyperpigmentation of the iris and periocular skin, increased hyperemia and periorbital erythema, and enophthalmos with a sunken, hollow orbit (not so good for Indians). A cautionary note should be attached that PGAs should not be prescribed for patients who already have “deep set eyes” (a deep upper eyelid sulcus), those who have had a blepharoplasty with periorbital fat resection, and people who have green or hazel-colored eyes (good for most Indians).
Potential candidates are citizens of North East India who want a more westernized appearance without surgery.Titration must be governed by deepening of the upper eyelid sulcus and diminishing dermatochalasis of the upper and lower eyelids and should be reduced to 2-3 times per week. If complications are noted, such as ptosis or inferior scleral show, appropriate titration or discontinuation of the drug is warranted.Topical bimatoprost holds promise as a potential agent for achieving periorbital rejuvenation beyond eyelash enhancement – a “chemical blepharoplasty.” Further research is required to establish safety and consistent efficacy of this ‘elixir in a bottle’.

9. Green nail syndrome (chromonychia) is a nail disorder characterized by onycholysis and green-black discoloration of the nail bed.Pseudomonas aeruginosa is the most commonly identified organism in cultures from the affected area (Ann Dermatol 26(4) 514-516, 2014). Despite the various treatment options available, surgical removal of the nail is still necessary in many cases. I came across this interesting scenario where patient had failed an oral antifungal agent (itraconazole,200 mg/d) and an oral antibiotic (levofloxacin,200 mg/d) for several weeks.P. aeruginosa was identified on culture. A sensitivity test was also performed, and the organism showed sensitivity to a few antibiotic agents, including tobramycin. Hence, a diagnosis ofpseudomonal green nail syndrome was established and tobramycin eye drop (3 mg/ml) was prescribed with good relief. The green-black discoloration of the nail is due to pyocyanin, an antibiotic pigment produced by the Gram-negative P. aeruginosa. History of long duration of exposure to water or moist conditions provides the ideal milieu for bacterial overgrowth. Other topicals used have been antiseptics such as chlorhexidine and 1% acetic acid. Of the oral antibiotics, levofloxacin and ofloxacin can be useful.

10. Any dermatologists’ nightmare is the entity called familial benign pemphigus (Hailey Hailey disease-HHD) which is benign but ‘festers in the flexures’ and causes severe quality of life impairment. This disease is caused by mutations in ATP2C1 gene encoding for the Golgi secretory pathway Ca2+/Mn2+-ATPase protein 1 (SPCA1).
Human keratinocytes use almost only this pump for loading the Golgi stores with Ca2+. It is plausible to speculate that a defective SPCA1 might affect the processing of desmosomal components, leading to the loss of epidermal suprabasal cell–cell adhesion and consequent acantholysis (International Journal of Dermatology 2015, 54, 543–548).
In my peregrinations of journals, I came across this article which mentioned the dramatic improvement in HHD by magnesium chloride hexahydrate (MgCl2) topical solution. A healthy 72-year-old woman with a history of biopsy-confirmed HHD localized on her vulva and inguinal folds presented to the authors. A great number of topical treatments, including corticosteroids, antifungals, antibiotics, antiseptics, zinc oxide paste and moisturizers, were only partially effective in controlling the disease.
She incidentally consumed magnesium chloride solution, for her co-existent arthritis, on the advice of her friend as a home remedy. The patient dissolved 33 g of magnesium chloride hexahydrate (MgCl2∙6H2O) in 1 l of water anddrank a coffee cup of the solution daily before breakfast, namely about 70 ml of the solution. Unexpectedly, one week after the beginning of the treatment with magnesium chloride hexahydrate, a significant improvement in the skin lesions was noted, and an almost complete remission of signs and symptoms was obtained after four weeks. On examination after three months of daily intake of magnesium chloride, complete re-epithelialization of the previously affected areas had occurred. This clinical improvement continued to persist after 12 months of ongoing treatment, including during the hot and humid summer period. No relevant relapses occurred, except for two exacerbations of HHD in situations of great stress.Desmosome assembly and adhesion are Ca2+-dependent processes.
In low Ca2+ conditions, desmosomes are not assembled, even if constituent proteins continue to be synthesized and stored in the Endoplasmic reticulum, where they are folded and processed prior to transport to the cell membrane. Ca2+ concentration in the basal layer of HHD lesions is lower than in the normal control skin. (J Invest Dermatol2009; 129: 1379–1387.). Because of the deficient Golgi Ca2+ pump, the restoration of the Golgi Ca2+ stores in HHD is slower than in normal keratinocytes. MgCl2 has an inhibitory effect on intracellularCa2+-extrusion machinery, favoring cytosolic and mitochondrial Ca2+ accumulation, which might explain its benefits (Biophys Res Commun1990; 169: 700–705.).
It is surprising that this finding has not been pursued in therapy of further HHD cases in literature. A promising result waiting to be disproven/reiterated!. This is a drug which has shown its wares and now the mechanism needs to retro- engineered. (Remember propranolol for hemangiomas!)

11. The evolution of ‘sun protection in a pill’ has been one of the biggest news in dermatological circles since last 5 years. The promise of a pill protecting from the vagaries of sunlight and which can substitute or add on to the efficacy of sunscreen use, particularly during those long beach vacations, will always be an interesting proposition. Polypodiumleucotomos (PL) offers such potential. Many agents such as ascorbate, tocopherol, or carotenoids have shown varying efficacy as a protector from UV light.
(J Am AcadDermatol2004; 51: 910–918.) . PL is a tropical fern, from the Phlebodiumgenus, found in Central and South America. It contains polyphenolic compounds, mainly benzoate and cinnamates; 4-hydroxycinnamic acid (caffeic acid) inhibits UV induced peroxidation and production of nitric oxide (NO), while its derivative, ferulic acid, is a UV photon acceptor. We are familiar with rejuvenatoryproperties of ferulic acid peels.
Owing to low toxicity and good absorption profile, PL has been shown to be a particularly interesting photoprotective agent. Heliocare has been a popular brand costing more than Rs 2000 for 30 pills. Newer indigenous options like Patchex(Meyer vitabiotics) and O-Screen (with alpha lipoic acid – Ethicare pharma) have provided less expensive options.
Anti-inflammatory action, DNA photoprotection, immunoregulation, and anticarcinogenic potential are the mouth watering effects of PL. Sunscreen use by patients is often suboptimal and depends on substantivity and needs to be applied even indoors. The proposition of having a sticky sunscreen glued to our skin for long periods is disconcerting.
It is this niche, which might be effectively covered by PL. The antioxidant action is explained by PL inhibiting glutathione oxidation in blood and epidermis by allosterically modulatingenzymes such as catalase (ExpDermatol2008; 17: 653–658.). A major clinical application will be in PUVA therapy. Acute phototoxicity and subsequent development of hyperpigmentation is a limiting factor in the use of PUVA therapy for skin disorders. A study has demonstrated that PL-treated skin showed a statistically lower grade of erythema and edema than sites exposed to PUVA alone.
By reducing hyperpigmentation and need for elevated doses, PL may contribute to amelioratethe safety profile of PUVA treatment (J Am AcadDermatol2004; 50: 41–49.). PL prevented the UV induced accumulation of Cyclobutane Pyrimidine Dimers(CPD) in a study demonstrating significantly lower levels of CPD in PL-treated skin compared to untreated healthy volunteers. (J Am AcadDermatol2004; 51: 910–918.). PL also inhibits the depletion of antigen-presenting cells such as epidermal Langerhans cells, hence safeguarding the skin’s immune surveillance compromised by UV light.
The anti-carcinogenic effects are due to inhibition of reactive oxygen radicals,inhibition of UV-induced Cox-2, activation of tumor suppressor p53, and boosting Langerhans cells role in tumor-specific immunity. PL promotes the regeneration of skin and compensates for the deleterious effects of radiation. (PhotochemPhotobiolSci2010; 9: 559–563.). The use of a systemic protective agent would provide significant advantages such as a more uniform coverage over the total body surface area, regardless of individual factors such as potency of the creams, amount applied, sweating, or bathing.
Thus the pluripotency of polypodiumleucotomos offers utopian benefits which need to be proven by rigorous RCTs before entrusting our skin to the vagaries of natures while consuming this agent.

Any particular facets of aesthetics and dermatologic therapy on similar lines as above which interests you can be mailed at This email address is being protected from spambots. You need JavaScript enabled to view it. . The same will be included in future columns with due acknowledgement to the contributor. After all feedback is the embellishment of any authorial venture!