The Aestheticians Journal I December'22 issue

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Published for the period of December-2022

To Keep Healthy Skin in Winter is The Real Challenge

The skin is a large, complex organ, and it serves as the body's primary interface with the environment, playing key roles in sensory, thermoregulatory, barrier, and immunological functioning. Many skin diseases are climate sensitive; sometime the changing climate is a significant threat to dermatological health. The winter season is the worst time for our skin, especially if we suffer from dryness. To keep healthy skin in winter is the real challenge. Some effective points to keep in mind to win against climate sensitive skin problems. During the winter season, impairment and fragility of the skin barrier is the most common thing, which can manifest as symptoms of dryness, sensitivity, and a lack of lustre look. Skin loses the natural moisture, in some cases; it can even lead to psoriasis, eczema, and other skin conditions.

To prevent these types of skin problems during the winter season, apply moisturising cleanser that can help to hydrate parched skin, and support the skin’s barrier to help protect the skin from the damaging effects of the cold weather. This also helps to wash away the dead skin cells, without leaving the skin feeling tight or dry. The key to keeping skin clean and free of accumulated dirt is cleansing twice a daily. Cleansing also increases the blood flow, and aids elimination of toxins. Dermatologists always help to suggest various steps that we can take to keep our skin happy.

In this issue we have the articles on Incontinentia Pigmenti, Video dermoscopy for Non-scarring Alopecia of Scalp, Management of Hyperpigmentation, and Cutaneous Herpes Zoster etc.

- Dom Daniel Executive Editor & Publisher

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

Dr. Abir Saraswat, MBBS, MD

A Rare Case Report of Disseminated Cutaneous ZosterAssociated Acute Urinary Retention in Immunocompetent Patient

Dr. Harshini Molugoori, 3rd Year Resident

Dr. Shivkumar Patil, MD

Dr. Bhavana R. Doshi, MD, DVD, FIDD

Incontinentia Pigmenti: A Rare Case Report

Dr. Archit Aggarwal, MBBS, M.D

Role of Liposomal 4-n-Butylresorcinol in the Management Hyperpigmentationof

Videodermoscopy Evaluation in Non-scarring Alopecia of Scalp Part-1

Dr. Palak Garg, MD (DVL)

Dr. Gaurav Rajauria, PharmD (Doctor of Pharmacy)

Editorial Board

Dr. Abir Saraswat

MBBS, MD

Dermatologist and Cosmetologist Indushree Skin Clinic, Lucknow, India

Dr. Bhavana R. Doshi

MD, DVD, FIDD

Professor and Head Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Dr. Shivkumar Patil

MD

Associate Professor Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Dr. Archit Aggarwal

MBBS, M.D (Dermatology)

Senior Resident Department of Dermatology Al Falah School of Medical Sciences, Faridabad

Dr. Palak Garg

MD (DVL)

Consultant Dermatologist Dr. Talwar's Skin, Hair and Laser Clinic Chandigarh, India

Dr. Gaurav Rajauria

PharmD (Doctor of Pharmacy) Assistant Professor Department of Pharmacy Dr. Bhimrao Ambedkar University, Chhalesar Agra, Uttar Pradesh, India

Dr. Harshini Molugoori

MBBS, 3rd Year Resident Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

Dr. Abir Saraswat MBBS, MD Dermatologist and Cosmetologist Indushree Skin Clinic, Lucknow, India

Abstract

Hyperpigmentation of skin is commonly caused due excessive production of melanin. Various natural and synthetic formulations are available for the treatment of hyperpigmentation. Every formulation has its own limitations. Among the available remedies, 4-n-butylresorcinol is reported to have potent tyrosinase inhibitory activity. The liposome encapsulation method is a novel drug delivery system that is used to improve the stability and penetration of a drug. Therefore, a liposomal formulation of 4-n-butylresorcinol has been prepared to overcome the penetration and stability issues of 4-n-butylresorcinol. The in vitro and in vivo evaluation of the liposomal formulation of 4-n-butylresorcinol showed enhanced efficacy and

safety.Liposome-encapsulated 4-n-butylresorcinol promises to be a potent and safe option for the treatment of hyperpigmentation.

Keywords

Melanin, Hyperpigmentation, Demelanising agents, Butylresorcinol, liposomal 4-n-Butylresorcinol

Introduction Hyperpigmentation

Pigmentation of the skin is very common in patients visiting dermatologists. Any alteration in melanin production or transport or distribution leads to skin pigmentation. Excessive melanin secretion leads to “Hyperpigmentation”. The key causes of hyperpigmentation of the skin are given in Figure 1.(1)

Figure 1: Key responsible factors of hyperpigmentation

Proper diagnosis of hyperpigmentation and investigation of the key underlying factors will help dermatologists to facilitate appropriate treatment. If hyperpigmentation of the skin is not treated in time it may worsen the psychological condition of patients. Therefore, early consultation, diagnosis and specific treatment can be helpful in effectively treating long-term conditions like melasma.(2) There are numerous remedies available for the treatment of melasma viz. hydroquinone, kojic acid, glycolic acid, chemical peels and laser therapy. Many of them can produce adverse effects like itching, hypersensitivity, inflammation, and post-inflammatory hyperpigmentation. Therefore, there is an urgent need for novel formulations that have better safety and efficacy compared to previous formulations and can serve the need of the current situation. This review article sheds light on the types of hyperpigmentation, currently available treatment options and their limitations, and novel treatment options and advantages.

Types of hyperpigmentation

Hyperpigmentation disorders can be classified in many different ways. Some of the commonest are:postinflammatory hyperpigmentation, melasma, solar lentigines, ephelides, and café au lait macules. They are depicted in Figure 2.

Figure 2: Types of hyperpigmentation disorders with salient clinical features

Post-inflammatory hyperpigmentation (PIH)

It is the most common result of inflammation, predominantly seen in darker skin types. The PIH lesions can persist from months to years and can be psychologically devastating to many patients. PIH presents as dark, irregular pigmented skin at sites of earlier injury or inflammation. It is the most common consequence of light or laser therapy or cryotherapy.

Figure 3: Pathogenesis of post-inflammatory hyperpigmentation

Figure 3

: Pathogene ation therapy

sis of post-in during PI

flammatory IH gives th

y hyperpigm e best resu

lts. Identific

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Combination therapy during PIH gives the best results. Identification of the underlying condition i.e. acne/eczema or both etc. can help rapid recovery. The recovery of hyperpigmentation is a very slow process hence the duration of therapy may extend from weeks to months.(3) The details of combination therapy are mentioned in Table 1. However, treatment can be started with hydroquinone followed by sequential chemical peels may give the best results in severe hyperpigmentation.

Table 1: Current treatment options for PIH

Hyperpigmentation Treatment options Active ingredients

PIH

Combination therapy

Kligman’s formula

Hydroquinone 2%, Tretinoin 0.025% and dexamethasone 0.1%

Modified Kligman’s formula e.g. Triluma Fluocinolone 0.01%, Hydroquinone 4% and Tretinoin 0.05%

Monotherapy

Melasma

Azelaic acid, Dexamethasone, Salicylic acid, Glycolic acid peels, Retinoids, and Laser treatments

Melasma is progressive, asymptomatic hypermelanosis which appears on face and less commonly on dorsal forearms. Melasma can be idiopathic in the vast majority of patients, and get aggravated due to excessive sun exposure. It may sometimes be associated with some medications such as anticonvulsants or oral contraceptives. Melasma is more common in women compared to men. It can be found in three typical patterns and the details are given in Table 2. Melasma patches are brown in colour and with variable enhancement under Wood’s light. The current treatment options for melasma are mentioned in Table 3. Combination triple therapy can produce adverse events which include post-procedure hyperpigmentation and skin irritation. Sunscreens are widely recommended to treat and prevent recurrences of melasma.(4)

Table 2: Typical pattern of melasmaand percentage

Solar lentigines

Solar

exposed

Role of Liposomal 4-n-Butylresorcinol in the Management of

Table 4: Current treatment options for solar lentigines

Hyperpigmentation Treatment options Active ingredients

Solar lentigines Topical therapy Hydroquinone, Retinoids Ablative therapy Chemical peels, cryotherapy, intense pulsed light, lasers

Combination therapy Retinoids such as tazarotene (0.1% cream), tretinoin (0.025% to 0.05%), and adapalene gel (0.1% or 0.3%)

USFDA approved OTC formulation Adapalene 0.1% gel

Chemical peels 30% to 35% trichloroacetic acid solution

Cryotherapy Liquid nitrogen

Ephelides

Ephelides is also known as freckles. These are small (1-2mm) and sharply defined macular lesions. Ephelides are may vary in color from red to brown. Ephelides mainly found on face, neck, arms, chest and legs. Ephelides are asymptomatic lesions and can be treated similarly to lentigines.(2) The current treatment options for ephelides are mentioned in Table 5.

Table 5: Current treatment options for ephelides

Hyperpigmentation Treatment options Active ingredients

Ephelides Similar to solar lentigines Cryotherapy, hydroquinone, azelaic acid, glycolic acid peels, and laser and other light-based therapies.1,12

Café au lait macules

Café au lait macules are present at birth or developed early in life. These are asymptomatic tan to brown epidermal macules (1-20 cm) found most commonly in the trunk. Café au lait macules occur due to an increase in melanin concentration in melanocytes.(2) The current treatment options for Café au lait macules are mentioned in Table 6.

Table 6: Current treatment options for Café au lait macules

Hyperpigmentation Treatment options

Café au lait macules Cosmetic treatments include laser therapy or surgical excision.

Current Demelanising agents

The potential targets for the treatment of hyperpigmentation include cell receptor antagonists and melanocyte, tyrosinase, melanosome transfer inhibitors and melanin degraders in keratinocytes. The most widely targeted approach is tyrosinase inhibitors. The details of the current demelanising agents are mentioned in Table 7.

3. Glycolic acid Desquamation of keratinocytes and epidermolysis

Liposomal

to solar-simulated radiation leading to sunburn

Retinoids-

Tretinoin (~ 1%)

(6) 4. Kojic acid Tyrosinase inhibitor Contact dermatitis (5) 5.

Adapalene (0.10.3%)

Inhibits the induction of melanogenesis and photoaging

Excessive skin dryness, redness, scaling and pruritus

(7) 6. Azelaic acid Tyrosinase inhibitor

Tazarotene (0.051%)

Burning or stinging, itchiness and dryness (7) 7. Niacinamide

Inhibits the transfer of melanosomes Dryness and irritation (8) 8. 4-n-butylresorcinol Tyrosinase inhibitor

Mild erythema and itching (9)

Second line treatment-Oral agents 1. Tranexamic acid

Inhibits UV-induced plasmin activity

Erythema, skin irritation, xerosis, and scaling (10) 2. Melatonin

Antioxidant (Increase in glutathione levels and a decrease in malondialdehyde levels)

Sleepiness, dizziness, and nausea (11) 3. Cysteamine hydrochloride (5%)

Antioxidant (Hydroxy radicals scavenging activity) Burning sensation (12) 4. Glutathione

Skin-lightening activity NA (13)

Chemical peels (can be combined with topical/oral agents) acts bydesquamation and removing the superficial topmost layers of the skin (Stratum corneum) 1.

Jessner's solution14% salicylic acid, 14% lactic acid, and 14% resorcinol in alcohol solution

PIH (14) 2. Tretinoin peels- 1% to 10% PIH (15) 3. Glycolic acid peels PIH (15) 4. Salicylic acid peels (20%–30%) PIH (14) 5. Trichloroacetic acid peels (10%–65%) PIH (16)

7

These anti-hyperpigmentation agents are widely used for the treatment of post-inflammatory hyperpigmentation, melasma, solar lentigines, ephelides, and café au lait macules. Before 2006, Hydroquinone (up to 5%) topical formulations were considered as a gold standard. Later, USFDA banned over-the-counter hydroquinone preparations due to reported carcinogenicity. Many topical hyperpigmentation agents such as Arbutin, Glycolic acid, 4-n-butylresorcinol; oral agents such as Tranexamic acid, Melatonin, Cysteamine hydrochloride and Kojic acid, Retinoids (Tretinoin, Adapalene, Tazarotene), Azelaic acid, Niacinamide and Glutathione have entered in the market. These agents are variably effective. However, they have their own limitations such as poor penetration rate, lack of epidermal targeting, very slow action and other side effects.

of hyperpigmentation. The major issues in natural product isolation are quality control and standardization. These natural compounds are very difficult to isolate due to their complex structure and are very costly compared to synthetic demelanising agents.

and have lesser side effects for the treatment of hyperpigmentation.

Now a days, many natural compounds such as Aloesin, Hesperidin, Ellagic acid, Silymarin, Glabridin, Alpha-Bisabolol and Liquirtin have come into the market and are used for the treatment

Chemica regenerat skin. Con novel the hyperpig Conventi Hence, th that may to seriou the drug content to Novel fo delivery and safet effects. T situation hyperpig

Oral hyperpigmentation agents are newer therapeutic options and are still under assessment compared with traditional topical hyperpigmentation agents. Evidence showed that oral hyperpigmentation agents have lesser adverse effects compared to topical treatments. However, oral hyperpigmentation agents are not very widely marketed/used as a stand-alone treatment. They are generally used as add-on therapy with topical hyperpigmentation agents.

Chemical peels are generally used to complete the removal of damaged skin and allow regeneration of the skin cells. But, they have a risk of inflammation and discoloration of the skin. Considering the limitations of all the conventional therapies, there is an urgent need for novel therapeutics which are safe to use

posome lid-lipid nano anosome ano/Micro em icrosponges rays & Foam

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Figure hyperpig Recent a drugs hav An ideall at the targ

al peelsareg tion of the s nsidering the erapeutics w gmentation. ional formul he drug distr exceed the us adverse ev concentratio o the site of ormulationsh by maintain ty, site-spec Therefore, no The nove gmentation ag 4: Novel f gmentation advances in t ve offered a ly designed get site with

vel formulati icroneedling atelet rich pla actional Photo

enerally us skin cells. Bu e limitations which are sa ations are u ibution in n targeted dos vents. Novel on in therape action as pe aveseveral ning desired ific delivery vel formula l formulat gents are me formulation agents he understa more ratio novel drug an appropri

Conventional formulations are unable to control the rate of drug delivery to the target site. Hence, the drug distribution in non-target tissue and body fluids necessitate therapeutic doses that may exceed the targeted dose in target cells. In some cases, the high drug dose may lead to serious adverse events. Novel drug delivery systems (NDDS) are carriers which maintain the drug concentration in therapeutic range for longer period of time. NDDS may deliver the content to the site of action as per requirements.

particles ulsion s

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ed to com ut, they hav of all the c fe to use an nable to co on-target tis e in target c l drug delive utic range f r requiremen advantages drug conce of drug wi tions of exi ions and o entioned in F s and oth nding of ph nal approac delivery sys iate rate.(17)

mplete the r e a risk of in onventional nd have les ontrol the rat sue and bod ells. In som ery systems or longer pe nts. over conv entration at th an optim sting drugs c other option Figure 4. er options armacokine h for the de stem(NDDS)

removal of nflammation therapies, th ser side eff e of drug d y fluids nec e cases, the (NDDS) are riod of time entional o a controlled mum dose an can be consi ns for the for the tic &pharma velopment o delivers a

f damaged and discol ere is an ur fects for the elivery to th cessitate ther high drug d e carriers wh e. NDDS ma nes, such a rate, enhan nd decreased idered to serv developme

Novel formulations have several advantages over conventional ones, such as controlled delivery by maintaining desired drug concentration at a controlled rate, enhanced efficacy and safety, site-specific delivery of drug with an optimum dose and decreased toxicity/side effects. Therefore, novel formulations of existing drugs can be considered to serve the current situation. The novel formulations and other options for the development of novel hyperpigmentation agents are mentioned in Figure 4.

skinandallow oration of th rgent need fo treatment o e target sit apeutic dose ose may lea ich maintai y deliver th s controlle nced efficac toxicity/sid ve the curren nt of nov

developme acodynamic of optimal d specified am

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Figure 4: Novel formulations and other options for the development of novel hyperpigmentation agents

Recent advances in the understanding of pharmacokinetic & pharmacodynamic behaviour of drugs have offered a more rational approach for the development of optimal drug delivery. An ideally designed novel drug delivery system (NDDS) delivers a specified amount of drug at the target site with an appropriate rate.(17)

Liposomes are vesicular structures consisting of phospholipids. Liposomes are microscopic vesicles in which drug is entirely enclosed by lipid bilayers. Many drugs have been formulated as liposomes to improve their therapeutic index.(18)

4-n-Butylresorcinol/ Rucinol in melasma

4-n-Butylresorcinol is obtained by POLA in 1998. Rucinolis a synthetic resorcinol derivative. Rucinol® inhibits melanin synthesis by inhibiting tyrosinase activity and tyrosinase-related protein-1 activity. Rucinol (0.3%) lotion is widely used for the treatment of hyperpigmentation disorders.(19)

Many natural flavonoids are known as whitening ingredients which contain the resorcinol motif. Resorcinol motif is mainly responsible for the powerful tyrosinase inhibition. Unfortunately, the bioavailability of flavonoids is very low. Therefore, scientists searched for smaller resorcinols which are highly effective and with good bioavailability.

Among various resorcinol derivatives, 4-butylresorcinol is identified as a strong tyrosinase and TRP-1 inhibitor with an IC50 of 13.5 lmol ⁄ L. Patients with age spots on the forearm were treated twice daily with a formula containing 4-n-butylresorcinol. Within 8 weeks, 4-n-butylresorcinol reduced visibly and the appearance of age spots, compared to

control group. In another study 4-butylresorcinol was more effective than 4-hexylresorcinol and 4-phenylethylresorcinol. The present literature showed that 4-butylresorcinol is a powerful human tyrosinase inhibitor with remarkable in vivo effectiveness. Topical products containing 4-butylresorcinol show strong efficacy on age spots, melasma and other facial hyperpigmentation.(20)

An in vitro study was carried out to evaluate the inhibition of skin hyperpigmentation by well-known compounds with skin whitening agents like hydroquinone, arbutin, kojic acid and 4-n-butylresorcinol. The study compared the inhibition of human tyrosinase activity in a biochemical assay as well as inhibition of melanin production in MelanoDerm skin model culture.

For some compounds, the in vivo efficacy was tested in clinical studies. Results showed that Arbutin and hydroquinone only weakly inhibit human tyrosinase with a half maximal inhibitory concentration (IC50) in the millimolar range. Kojic acid is 10 times more potent with an IC50 of approximately 500 lmol ⁄ L. However, by far the most potent inhibitor of human tyrosinase is 4-n-butylresorcinol with an IC50 of 21 lmol ⁄ L. In artificial skin models, arbutin was least active with an IC50 for inhibition of melanin production> 5000 lmol ⁄ L. Kojic acid inhibited with an IC50> 400 lmol ⁄ L. Interestingly, hydroquinone inhibited melanin production in MelanoDerms with an IC50 below 40 lmol ⁄ L, probably due to a mechanism different from tyrosinase inhibition. Again, 4-n-butylresorcinol was the most potent inhibitor with an IC50 of 13.5 lmol ⁄ L. In vivo efficacy of 4-n-butyl-resorcinol was confirmed in clinical studies. Subjects with age spots on the forearm treated twice daily with a formula

containing 4-n-butylresorcinol and two control age spots with the corresponding vehicle. Within 8 weeks, 4-n-butylresorcinol reduced visibly the appearance of age spots, while the control spots showed no improvement. A second study showed that 4-butylresorcinol was more effective than 4-hexylresorcinol and4-phenylethylresorcinol. The in vitro and in vivo data showed that the high inhibitory capacity of 4-n-butylresorcinol on human tyrosinase activity, exceeding by far the potency of hydroquinone, arbutin and kojic acid. The resulting clinical improvement of skin hyperpigmentations reveals 4-n-butylresorcinol as a very valuable active compound for the management of pigmentation disorders.(20)

Huh and co-workers carried out randomized, double-blind, vehicle-controlled, split-face comparative study to evaluate the hypopigmenting efficacy and safety of 4-n-butylresorcinol 0.1% cream for the treatment of melasma. 20 patients with melasma treated with 4-n-butylresorcinol 0.1% cream or vehicle to each side of the face twice daily for 8 weeks. Mexameter measurements results showed that the melanin index of the of 4-n-butylresorcinol 0.1% cream treated side showed a significant decrease in melasma with mild adverse reactions when compared with that of the vehicle-treated side after 4 and 8 weeks. The study concluded that, 4-n-butylresorcinol 0.1% cream has rapid efficacy and well tolerated in patients with melasma.(9)

A study was carried out by Sreeja and co-workers to compare the efficacy of modified Kligman's regimen with the following combination which includes 4-n

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

–butylresorcinol, liquorice extract and ɑ-Arbutin in the treatment of melasma. 50 melasma patients (out of which 96% patients were females) were included in this study. Group A (n=25) was treated with modified Kligman's regimen and group B (n=25) was treated with 4-butylresorcinol, liquorice extract and ɑ-Arbutin. The mean modified melasma area severity index score was decreased in both groups indicating that both groups showed significant improvement during the study period. The subjective assessment for patient satisfaction was 34.7% in group A and 30.2 % in group B after 8 weeks of treatment. The study reported that pigmentation was decreased in both group. The study concluded that combination of 4-n –butylresorcinol, ɑ-Arbutin and liquorice extract had lesser side effects compared to modified Kligman'sregimen.(21)

The main objective of using liposomes as drug carriers is to attain selective and sufficiently high concentration of active drug at the site of applications. Liposomes are nontoxic in nature and are easily re-absorbed from the epidermis into the deepest layers of skin. The encapsulation of drugs into liposomes, for topical use, gives a higher drug concentration at the site of action, thereby enhancing the localized effects but at the same time minimizing the side effects. Thus the topical application of liposomes offer a wide range of advantages including increased moisturization, restoring action, biodegradability, biocompatibility and extended and slow dermal release.(18) Hence, liposomal 4-butylresorcinol was prepared to enhance the bioavailability and effectiveness with less side effects.

Clinical trials of liposomal 4-n-butylresorcinol

A randomized, double-blind, vehicle-controlled and splitface comparison study was carried out in 2009 to evaluate the hypopigmenting efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream in 23 Korean patients with melasma. 4-n-butylresorcinol 0.1% cream or vehicle was applied to each side of the face twice daily for 8 weeks. All subjects completed the study. Mexameter measurements showed that the melanin index of the 4-n-butylresorcinol-treated side showed a significant decrease when compared with the vehicletreated side after 8 weeks. No adverse reactions were observed throughout the study. Subjectively, 4-n-butylresorcinol was considered to be efficacious in more than 60% of the patients after 8 weeks of treatment. The study concluded that liposome-encapsulated 4-n-butylresorcinol 0.1% cream was well tolerated and showed significant higher efficacy than vehicle alone for the treatment of melasma.(22)

In a prospective, double-blind, randomized, vehicle-controlled, split-face comparative trial, 32 females with melasma were treated with rucinol serum 0.3% or vehicle, which was applied twice daily for 12 weeks followed by a 12-week follow-up. After 12 weeks, clinical pigmentation scores were lower than the vehicle-treated site, and the difference was statistically significant. The study demonstrated the tolerability and efficacy of rucinol in melasma. A recent modification of 0.3% serum into 0.1% liposomal cream, which leads to an improved stabilization and enhanced penetration, has been studied to be effective in melasma.(23)

Another study was carried out to evaluate efficacy and safety of a cream which contains liposomeencapsulated 4-n-butylresorcinol (4nBR) and Resveratrol (RSV) in the treatment of melasma. A total of 21 female patients with melasma were treated with the cream for 4 weeks. The results showed that the lesional MI was significantly decreased at weeks 2 and 4 compared with the baseline while no significant change in the nonlesional MI was observed throughout the study. The mean investigator's global assessment score was also significantly improved at weeks 2 and 4. In patient's self-assessment, 8 (38.1%) and 11 (52.3%) patients answered moderate to significant improvement in their melasma at weeks 2 and 4, respectively. No serious adverse events were reported. The study concluded that cream containing liposomeencapsulated 4nBR and RSV was shown to be effective and safe for the treatment of melasma with its effect appearing as early as 2 weeks.(24)

Another study was carried out to check the effects of 4-n-butylresorcinol and/or resveratrol on melanogenesis. To achieve synergistic effects and avoid potential adverse effects, combinations of the agents in low concentrations were used. Results showed that 1 microM of 4-n-butylresorcinol and 1 microM of resveratrol did not individually inhibit melanin synthesis. However, the combination of 4-n-butylresorcinol (1 microM) and resveratrol (1 microM) significantly reduced melanin synthesis. Furthermore, 4-n-butylresorcinol (10 microM) and resveratrol (10 microM) decreased melanogenesis in a much stronger way. 4-n-butylresorcinol is reported to directly inhibit tyrosinase, the

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

rate-limiting melanogenic enzyme, without changing tyrosinase levels. Results also showed that resveratrol did not directly inhibit tyrosinase at 0.1-10 microM. Literature has reported that resveratrol led to posttranscriptional regulation of tyrosinase. However, Western blot analysis showed that neither 4-n-butylresorcinol nor resveratrol alone decreased tyrosinase protein levels. Surprisingly, the combination of 4-n-butylresorcinol and resveratrol reduced tyrosinase levels. The study concluded that the synergistic hypopigmentary effect of 4-n-butylresorcinol and resveratrol results from a decreased level of tyrosinase possibly resulting from synergistic action of 4-n-butylresorcinol on tyrosinase alteration by resveratrol.(25)

Indian skin is more prone to irritation with hypopigmenting agents, study was done to explore the efficacy, safety, and tolerability of 4-n-butylresorcinol 0.3% cream in Indian subjects with melasma. 52 subjects with melasma recruited in the open-label, single arm, observational study. All the patients were advised twice daily application of 4-n-butylresorcinol 0.3% cream for 8 weeks over the areas of melasma. All the 52 subjects completed the study. Out of 52 subjects, 90.38% were females. Results showed that the Mean ± standard error of MASI score was significantly decreased from baseline score of 14.73±0.59 to 11.09±0.53 after week 4 and 6.48±0.43 at week 8. The digital photographs of the study subjects taken at week 4 and week 8 also showed decrease in melasma pigmentation compared to baseline photograph and correlated with the changes in the mMASI score. The treatment was well tolerated by all the study subjects. No

adverse reactions were reported throughout the study period.

The study concluded that the 4-n-butylresorcinol 0.3% cream is safe, effective, and well tolerated in Indian patients with melasma.(26)

A prospective, single-centre, double-blind, randomized, vehiclecontrolled, bilateral (split-face) comparative trial study was carried out to assess the efficacy of rucinol serum 0.3% vs. the corresponding vehicle as a treatment for melasma. Secondary objective was to evaluate local and general tolerability and to assess the skin acceptability of rucinol serum in the target population. Total 32 women with melasma were treated with two identical tubes containing rucinol serum 0.3% or vehicle. The products were each applied to onehalf of the face, according to the randomization scheme, twice daily for 12 weeks (phase 1). A broadspectrum sunscreen (sun protection factor 60) was also applied daily. After 12 weeks, patients were given the option of an additional 3-month treatment period of open full-face rucinol treatment, with reviews at 16, 20 and 24 weeks (phase 2). Results showed that 28 patients completed phase 1 and 26 patients completed phase 2. After 12 weeks, the clinical pigmentation score for rucinol-treated skin was significantly lower than for vehicletreated skin. During phase 2, rucinol induced a significant reduction in mean pigmentation score on the half of the face previously treated with vehicle. There was also a further, significant improvement on the rucinol-treated side of the face. Chromametry measurements showed that skin was significantly lighter and less yellow, with a strong trend towards reduced redness, following rucinol therapy compared with vehicle. Rucinol serum showed good tolerability and acceptability

and was considered to have good or fair efficacy by 78% of the patient population. The study concluded that Rucinol serum have significant efficacy compared with vehicle alone in improving melasma after 3 months of treatment, according to clinical and objective assessments of skin colour.(27)

Conclusion

Hyperpigmentation is a chronic distressing condition that is often recalcitrant to various demelanising treatment modalities. 4-n-butylresorcinol is a newly developed hypopigmentation agent that has an inhibitory effect against both tyrosinase and TRP-1. Liposome-encapsulated 4-n-butylresorcinol- containing formulations showed rapid efficacy and safety compared to other treatment options.

References

1. Lipsker D, Lenormand C. Hyperpigmentation. Ann Dermatol Venereol [Internet]. 2019 Oct 1 [cited 2022 Aug 12];146(10):666–82. Available from: https:// pubmed.ncbi.nlm.nih.gov/31537319/

2. Plensdorf S, Livieratos M, Dada N. Pigmentation Disorders: Diagnosis and Management. Am Fam Physician [Internet]. 2017 Dec 15 [cited 2022 Aug 12];96(12):797–804. Available from: https:// pubmed.ncbi.nlm.nih.gov/29431372/

3. Shenoy A, Madan R. Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies. J Drugs Dermatol [Internet]. 2020 Aug 1 [cited 2022 Sep 16];19(8):763–8. Available from: https://pubmed.ncbi.nlm.nih. gov/32845587/

4. Rajanala S, Maymone M, Vashi N. Melasma pathogenesis: a review of the latest research, pathological findings, and investigational therapies - PubMed. Dermatol Online J [Internet]. 2019 Oct 15 [cited 2022 Sep 16];25(10). Available from: https:// pubmed.ncbi.nlm.nih.gov/31735001/

5. Nautiyal A, Wairkar S. Management of hyperpigmentation: Current treatments and emerging therapies. Pigment Cell Melanoma

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

Res [Internet]. 2021 Nov 1 [cited 2022 Sep 15];34(6):1000–14. Available from: https:// pubmed.ncbi.nlm.nih.gov/33998768/

6. Kornhauser A, Coelho SG, Hearing VJ. Applications of hydroxy acids: classification, mechanisms, and photoactivity. Clin Cosmet Investig dermatology CCID [Internet]. 2010 Nov [cited 2022 Sep 15];3:135. Available from: /pmc/articles/PMC3047947/

7. Woolery-Lloyd H, Keri J, Doig S. Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of colorPubMed. J Drugs Dermatol [Internet]. 2013 Apr 1 [cited 2022 Sep 15];12(4):434–7. Available from: https://pubmed.ncbi.nlm.nih. gov/23652891/

8. Chen AC, Damian DL. Nicotinamide and the skin. Australas J Dermatol [Internet]. 2014 [cited 2022 Sep 15];55(3):169–75. Available from: https://pubmed.ncbi.nlm.nih. gov/24635573/

9. Huh SY, Shin JW, Na JI, Huh CH, Youn SW, Park KC. The Efficacy and Safety of 4-n-butylresorcinol 0.1% Cream for the Treatment of Melasma: A Randomized Controlled Split-face Trial. Ann Dermatol [Internet]. 2010 Feb [cited 2022 Sep 16];22(1):21. Available from: /pmc/articles/ PMC2883392/

10. Ebrahimi B, Naeini FF. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci [Internet]. 2014 [cited 2022 Sep 15];19(8):753. Available from: /pmc/articles/ PMC4235096/

11. Rusanova I, Martínez-Ruiz L, Florido J, Rodríguez-Santana C, Guerra-Librero A, Acuña-Castroviejo D, et al. Protective Effects of Melatonin on the Skin: Future Perspectives. Int J Mol Sci [Internet]. 2019 Oct 1 [cited 2022 Sep 15];20(19). Available from: /pmc/articles/PMC6802208/

12. Desai S, Hartman C, Grimes P, Shah S. Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines. J Drugs Dermatol [Internet]. 2021 Dec 1 [cited 2022 Sep 15];20(12):1276–9. Available from: https://pubmed.ncbi.nlm.nih.gov/34898155/

13. Sonthalia S, Jha AK, Lallas A, Jain G, Jakhar D. Glutathione for skin lightening: a regnant myth or evidence-based verity?

Dermatol Pract Concept [Internet]. 2018 Jan 31 [cited 2022 Sep 15];8(1):15. Available from: /pmc/articles/PMC5808366/

14. How KN, Lim PY, Wan Ahmad Kammal WSL, Shamsudin N. Efficacy and safety of Jessner’s solution peel in comparison with salicylic acid 30% peel in the management of patients with acne vulgaris and postacne hyperpigmentation with skin of color: a randomized, double-blinded, split-face, controlled trial. Int J Dermatol [Internet]. 2020 Jul 1 [cited 2022 Sep 15];59(7):804–12. Available from: https://pubmed.ncbi.nlm.nih. gov/32447767/

15. Sarkar R, Garg V, Bansal S, Sethi S, Gupta C. Comparative Evaluation of Efficacy and Tolerability of Glycolic Acid, Salicylic Mandelic Acid, and Phytic Acid Combination Peels in Melasma. Dermatol Surg [Internet]. 2016 Mar 23 [cited 2022 Sep 15];42(3):384–

91. Available from: https://pubmed.ncbi.nlm. nih.gov/26859648/

16. Kumari R, Thappa D. Comparative study of trichloroacetic acid versus glycolic acid chemical peels in the treatment of melasma. Indian J Dermatol Venereol Leprol [Internet]. 2010 Jul [cited 2022 Sep 15];76(4):447. Available from: https://pubmed.ncbi.nlm.nih. gov/20657143/

17. Gao H, Jiang X. The progress of novel drug delivery systems [Internet]. Yao Xue Xue Bao. 2017 [cited 2022 Sep 16]. p. 181–8. Available from: https://pubmed.ncbi.nlm. nih.gov/29979498/

18. Guimarães D, Cavaco-Paulo A, Nogueira E. Design of liposomes as drug delivery system for therapeutic applications. Int J Pharm [Internet]. 2021 May 15 [cited 2022 Sep 16];601. Available from: https:// pubmed.ncbi.nlm.nih.gov/33812967/

19. Ando H, Matsui MS, Ichihashi M. Quasidrugs developed in Japan for the prevention or treatment of hyperpigmentary disorders. Int J Mol Sci [Internet]. 2010 Jun [cited 2022 Sep 19];11(6):2566–75. Available from: https://pubmed.ncbi.nlm.nih.gov/20640168/

20. Kolbe L, Mann T, Gerwat W, Batzer J, Ahlheit S, Scherner C, et al. 4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation. J Eur Acad Dermatol Venereol [Internet]. 2013 [cited 2022 Sep

19];27 Suppl 1(SUPPL. 1):19–23. Available from: https://pubmed.ncbi.nlm.nih. gov/23205541/

21. Sreeja D, Haritha V, Latha MM. A comparative study of modified kligmans regimen with a combination of 4-n-butylresorcinol, ɑ-arbutin and licorice extract in the treatment of melasma. MedPulse Int J Med. 2020;13(2):73.

22. Huh SY, Shin JW, Na JI, Huh CH, Youn SW, Park KC. Efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream for the treatment of melasma: a randomized controlled split-face trial. J Dermatol [Internet]. 2010 Apr [cited 2022 Sep 19];37(4):311–5. Available from: https:// pubmed.ncbi.nlm.nih.gov/20507399/

23. Sarkar R, Chugh S, Garg VK. Newer and upcoming therapies for melasma. Indian J Dermatol Venereol Leprol [Internet]. 2012 Jul [cited 2022 Oct 15];78(4):417–28. Available from: https://pubmed.ncbi.nlm.nih. gov/22772611/

24. Kwon SH, Yang JH, Shin JW, Park KC, Huh CH, Na JI. Efficacy of liposomeencapsulated 4-n-butylresorcinol and resveratrol cream in the treatment of melasma. J Cosmet Dermatol [Internet]. 2020 Apr 1 [cited 2022 Sep 19];19(4):891–5. Available from: https://pubmed.ncbi.nlm.nih. gov/31347777/

25. Kim S, Park K, Kwon S, Kim D. Hypopigmentary effects of 4-n-butylresorcinol and resveratrol in combination - PubMed. Pharm [Internet]. 2012 Jun 1 [cited 2022 Oct 15];67(6):542–6. Available from: https:// pubmed.ncbi.nlm.nih.gov/22822544/

26. Madan Mohan NT, Gowda A, Jaiswal AK, Sharath Kumar BC, Shilpashree P, Gangaboraiah B, et al. Assessment of efficacy, safety, and tolerability of 4-n-butylresorcinol 0.3% cream: an Indian multicentric study on melasma. Clin Cosmet Investig Dermatol [Internet]. 2016 Jan 21 [cited 2022 Oct 15];9:2–21. Available from: https://pubmed.ncbi.nlm.nih.gov/26855596/

27. Khemis A, Kaiafa A, Queille-Roussel C, Duteil L, Ortonne JP. Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial. Br J Dermatol [Internet]. 2007 May [cited 2022 Oct 15];156(5):997–1004. Available from: https://pubmed.ncbi.nlm.nih.gov/17388924/

Role of Liposomal 4-n-Butylresorcinol in the Management of Hyperpigmentation

New signaling pathway to combat UV damage and skin infection

As the largest organ of the human body, the skin literally provides a major barrier exposed to environmental stimuli and pathogens. Painful inflammation can be mounted if this barrier is compromised as anyone who has ever had a sunburn knows. Inflammatory reactions in the skin can reduce damage from UV radiation or infections, but can also result in painful symptoms such as sunburn. A recent study has now identified a molecular control which integrates these stress signals and researcher took a closer look at the processes involved.

UV light is very high in energy. When it hits the skin, it can therefore damage important cellular molecules, sparking inflammation as a common consequence. However, it was unclear how this exactly happens. Researcher has now been able to show that a known cellular stress signaling pathway can trigger these inflammatory responses.

The cell's own "engineering offices," the ribosomes, normally assemble proteins based on the instructions in the genetic material. When this is impaired due to UV damage, they sound the alarm: They trigger the so-called ribotoxic stress response. It has been known for years that this causes a signaling cascade resulting in the activation of an enzyme called p38. Their research shows that p38 molecularly modifies NLRP1, a critical switch for inflammation in the skin, and thus activates it in a novel way. This initiates the assembly of inflamma somes from many molecular building blocks. Inflamma somes are powerful weapons of the innate immune system. Among other things, these complex molecular machines can convert inactive messenger substances for inflammation into their active form. At the same time, they ensure that numerous holes are formed in the cell membrane. This allows messenger substances to reach the outside and thus call the body's own defense forces to its aid. Ultimately, the holes lead to the death of the cell: At some point, it practically explodes and empties its contents into the tissue. The molecules that are now abruptly released from within the cell are another warning sign for the immune system.

High molecular weight hyaluronic acid with amino acid effective in perioral rejuvenation

Skin aging is a complex biologic process influenced by a combination of intrinsic and extrinsic factors. Aging skin shows wrinkles, uneven tone, loss of elasticity, and thinning.Many investigations have been conducted that demonstrate the beneficial effects of [hyaluronic acid] and a cluster of [amino acids] in ulcers and other wounds. The recent study demonstrated a novel application of this medical device in the aesthetic and anti-aging fields.Individuals who underwent high molecular weight hyaluronic acid and amino acid injections showed significant improvement in the perioral area, according to an observational study.

The study evaluated the effects of an injectable formula containing high molecular weight hyaluronic acid (HMW HA) and a cluster of amino acids (AAs). HA has moisturizing and rejuvenating effects, and HMW HA has anti-inflammatory properties, degrades slowly, inhibits the production of proinflammatory mediators, reduces toll-like receptor expression and regulates angiogenesis. Further, HA is an “excellent vehicle” for AAs, which assist in the production of collagen.The open-label observational study included 37 women aged 40 to 65 years who showed signs of aging in the perioral area. Each patient received three sessions of monthly intradermal injections of 2.5 mL of the solution containing HMW HA with AAs. A local anesthetic cream containing lidocaine and prilocaine was applied to the skin 40 minutes before the injection.

Investigators followed up with patients 180 days after the first treatment to assess outcomes based on the Global Aesthetic Improvement Scale (GAIS) questionnaire, which determines scores based on five categories: dryness, desquamation, wrinkles, lack of tone and size of pores.The results of the GAIS showed that 89% of patients found their appearance “much improved” or “very much improved” and 11% of patients considered their appearance to be “slightly improved.” An objective evaluation by investigators also showed a consistent trend of improvement in all five categories.Additionally, patients reported satisfaction due to the lack of side effects, with 16.2% of patients experiencing slight bruising and swelling at the injection point.The treatment protocol produced natural and subtle results, without an unwanted volume,” Investigator wrote. Further investigations with a larger number of patients and a longer follow-up period should be conducted to verify these findings.

A Rare Case Report of

Disseminated Cutaneous ZosterAssociated Acute Urinary Retention in Immunocompetent Patient

Dr. Harshini Molugoori

3rd Year Resident

Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Dr. Shivkumar Patil

MD

Associate Professor

Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Dr. Bhavana R. Doshi

MD, DVD, FIDD

Professor and Head

Department of Dermatology, Venereology and Leprosy Jawaharlal Nehru Medical College, Belgaum, Karnataka

Abstract

Background

Disseminated cutaneous herpes zoster in healthy persons with acute urinary retention is an uncommon event, though it has been described in immune compromised patients.

Case presentation

We describe a case of disseminated cutaneous herpes zoster in a middle-aged immune competent man with acute urinary retention with no apparent immune suppressive condition. The patient was treated

successfully with intravenous Acyclovir.

Conclusion

We suggest that disseminated cutaneous zoster can occur in an immune competent host with systemic manifestations and should be promptly recognized and treated to prevent serious complications. Endeavorto increase the uptake of zoster vaccination should be brought to practise.

Introduction

Herpes zoster is one of the most commonly encountered dermatological diseases. It is caused by the varicella-zoster virus (VZV), dormant in the dorsal root ganglion, causing grouped vesicles and pain. Interestingly, VZV is capable of reactivating, where it can then cause symptoms at a time later than the initial infection. Risk factors for reactivation of VZV include older age and immune compromised status. VZV is considered to be transmitted via the airborne route, through inhalation of the virus aerosolized from the respiratory tract as well as through contact with the vesicle fluid and respiratory secretions. On rare occasions, symptoms may become severe enough that hospitalization may be required, such as in cases of disseminated herpes zoster.

The lifetime risk of herpes zoster in the general population ranges from 20–30% but the risk increases dramatically after 50 years of age with a lifetime risk of herpes zoster reaching 50% at age 85.1

Literature review

Herpes zoster is caused by the reactivation of the latent varicellazoster virus. One of the feared complications of this disease is disseminated herpes. A patient might have a few scattered lesions outside of their sharply demarcated and localized rash in about 33% of immunocompetent patients. However, once greater than 20 such lesions are identified outside these discrete areas of cutaneous involvement, a diagnosis of disseminated herpes zoster can be made. This occurs in 2% of the general population and about 15%-30% of cases in immune compromised patients.2 Once disseminated disease is identified, a concern is raised for the possible

unknown immune compromised state as well as other significant complications. Thus, sometimes a fairly simple clinical diagnosis can give way to a longer and more concerning differential as well as patient disposition dilemma.

Elsberg et al. reported for the first time that herpes zoster may cause urinary retention, and since then, urinary retention caused by herpes zoster has been occasionally reported;3 however, comparatively, this is still considered rare. To date, a total of 23 immuno competent patients have been reported to develop disseminated zoster2-21 and there is striking increase in incidence of cases post covid pandemic.

Case Report

A 55-year-old man (height 147 cm; weight 75 kg) visited the tertiary hospital with complaints of back pain, pain in the left buttock, and urinary retention that had started two days prior. The patient also had a history of blood discharge on passing stools x 2 days. He visited our department with painful lesions all over body and on initial physical examination, he had a temperature of 37.6°C, blood pressure of 130/70 mm Hg, and a heart rate of 77 beats per minute. Flaccid grouped vesicles were observed in the S1, and S2 nerve branch regions as a plaque with erosions, extending from the right buttock to the scrotum and anus. The patient was diagnosed with disseminated herpes zoster due to the presence of blisters with red base scattered on the trunk. Serology, blood sampling and tzank smear were done on the day of consultation showed multinucleated syncytial giant cells which are bipolar containing multiple nuclei in jigsaw puzzle like fashion with sero negative status. No associated comorbidities were found. Two days after the onset, the

patient was hospitalized (Day 0) and began treatment with an injection acyclovir (600 mg/day). In addition to indwelling urinary catheter, capsule silodosin at 8 mg/day was initiated for urinary retention. After admission, the patient had bowel incontinence on day 1. With continued acyclovir treatment, there is no appearance of new lesions, crusting of preexisting lesions , his pain was alleviated, and the urinary tract catheter was ultimately removed on day 15, following which there was no recurrence of urinary retention.

Figure 2: Multiples flaccid vesicles with erosions present over erythematous base involving S2, S3 dermatomes

Conclusion

This case serves as a reminder for the careful physical examination in patients with the usually simple,

of Disseminated Cutaneous Zoster - Associated Acute Urinary Retention in Immunocompetent Patient

Figure 1: Multiple grouped vesicles coalescing to form a plaque over the right L5, S1, S2, S3 dermatome

clinical diagnosis of herpes zoster. The most common complication will continue to be post-herpetic neuralgia. However, the more serious complications of the disease should be carefully considered by taking the patient's history and physical examination in each patient presenting with herpes zoster regardless of their immune status. These severe complications will continue to be more common in the immune compromised population but cannot be ignored in the general population. Efforts to increase the uptake of zoster vaccination should be endeavoured.22

References

1. Drone E, Ganti L. A Case of Disseminated Zoster in an Immuno competent Patient. Cureus. 2019;11(12):e6286. Published 2019Dec 4. doi:10.7759/ cureus.6286

2. O'Toole EA, Mooney EE, Walsh JB, Sweeney EC, Barnes L. Disseminated herpes zoster in the elderly. Ir J Med Sci. 1997 Jul-Sep;166(3):141-2. doi: 10.1007/ BF02943592. PMID: 9256548.

3. Yuta Norimatsu, Yuki Ohno. Disseminated herpes zoster infection with urinary retention and incontinence. International Journal of Infectious Diseases and Therapy. Vol. 5, No. 3, 2020, pp. 48-50. doi:10.11648/j. ijidt.20200503.12

4. Moriuchi H, Moriuchi M, Sun CC, Trucksis M. Disseminated cutaneous zoster and aseptic meningitis in a previously healthy patient. J Infect. 1997 Sep;35(2):183-5. doi: 10.1016/s0163-4453(97)91842-9. PMID: 9354356.

5. Dirbas FM, Swain JA. Disseminated cutaneous herpes zoster following cardiac surgery. J Cardiovasc Surg (Torino). 1990 Jul-Aug;31(4):531-2. PMID: 2211810.

6. Moriuchi H, Moriuchi M, Sun CC, Trucksis M. Disseminated cutaneous zoster and aseptic meningitis in a previously healthy patient. J Infect. 1997;35(2):183-185. doi:10.1016/ s0163-4453(97)91842-9

7. Beby-Defaux A, Brabant S, Chatellier D, et al. Disseminated varicella with multiorgan failure in an immunocompetent adult. J Med Virol. 2009;81(4):747-749. doi:10.1002/ jmv.21447

8. Goyal H, Thakkar N, Bagheri F, Srivastava S. Herpes zoster meningitis with multi dermatomal rash in an immunocompetent patient. Am J Emerg Med. 2013;31(11):1622. e1-2. doi:10.1016/j.ajem.2013.06.021

9. Kangath RV, Lindeman TE, Brust K. Herpes zoster as a cause of viral meningitis in immunocompetent patients. BMJ Case Rep. 2013;2013: bcr2012007575. doi:10.1136/ bcr-2012-007575

10. Oladokun RE, Olomukoro CN, Owa AB. Disseminated herpes zoster ophtha lmicus in an immune competent 8-year old boy. Clin Pract. 2013;3(2):e16. doi:10.4081/cp.2013. e16

11. Sun ZH, Guo YY, Li M, Yao ZR. Disseminated herpes zoster in immunocompetent patients not due to varicella-zoster virus gene mutation. Chin Med J (Engl). 2013;126(16):3193.

12. Takaoka Y, Miyachi Y, Yoshikawa Y, Tanioka M, Fujisawa A, Endo Y. Bilateral disseminated herpes zoster in an immunocompetent host. Dermatol Online J. 2013;19(2):13.

13. Yoon KJ, Kim SH, Lee EH, Choi JH. Disseminated herpes zoster in an immunocompetent elderly patient. Korean J Pain. 2013;26(2):195-198. doi:10.3344/ kjp.2013.26.2.195

14. Gomez E, Chernev I. Disseminated cutaneous herpes zoster in an immune ocompetent elderly patient. Infect Dis Rep. 2014;6(3):5513. doi:10.4081/idr.2014.5513

15.Kashyap S, Shanker V. Zoster ophthal micus with dissemination in a six year old immunocompetent child. Indian J Dermatol VenereolLeprol. 2014;80(4):382. doi:10.4103/ 0378-6323.136997

16. Petrun B, Williams V, Brice S. Disseminated varicella-zoster virus in an immunocompetent adult. Dermatol Online J. 2015;21(3):13030/qt3cz2x99b.

17. Scotch AH, Hoss E, Orenstein R, Budavari AI. Disseminated varicella-zoster virus after vaccination in an immunocompetent patient. J Am Osteopath Assoc. 2016;116(6): 402405. doi:10.7556/jaoa.2016.082

18. Rudinsky DM, Jordan K. Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient. BMJ Case Rep. 2017;2017: bcr2017220542. doi:10.1136/bcr-2017220542

19. Uchida K, Teske N, Christensen J. Disseminated zoster after trauma in an immune competent patient. Am J Med. 2017; 130(12):e539-e540. doi:10.1016/j. amjmed.2017.06.021 23. Lim ZV, Tey H. Disseminated herpes simplex virus and varicella zoster virus co-infection in an immunocompetent patient. Indian J Dermatol Venereol Leprol. 2018;84(2): 212214. doi:10.4103/ijdvl.IJDVL_423_17

20. Chakraborty U, Chandra A, Sil A, Biswas SK. Elderly immune competent man presenting with disseminated cutaneous herpes zoster. BMJ Case Rep. 2020;13(8):e237480. doi:10.1136/bcr-2020237480 25. Oh JH, Tummala S, Husnain MG. Disseminated herpes zoster with acute encephalitis in an immunocompetent elderly man. BMJ Case Rep. 2020;13(6):e232928. doi:10. 1136/bcr-2019-232928

21. Sohal RJ, Sohal S, George T, Gilotra T. Varicella-zoster meningitis with hypogly corrhachia in an immune competent patient presenting with disseminated varicellazoster infection. Cureus. 2020;12(6):e8539. doi:10.7759/cureus. 8539 27. Matsuo Y, Igarashi Y, Aoyama N, et al. Visceral disseminated varicella-zoster virus infection in an immune competent host. Clin J Gastroenterol. 2022;15(3):568-574. doi:10. 1007/s12328-022-01607-7

22. Kawai K, Yawn BP. Risk Factors for Herpes Zoster: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2017 Dec;92(12):1806-1821. doi: 10.1016/j. mayocp.2017.10.009. PMID: 29202939.

of Disseminated Cutaneous Zoster - Associated Acute Urinary Retention in Immunocompetent Patient

Incontinentia Pigmenti: A Rare Case Report

Dr. Archit Aggarwal

M.B.B.S, M.D (Dermatology) Senior Resident Department of Dermatology Al Falah School of Medical Sciences, Faridabad

Introduction

Incontinentia pigmenti (IP) also known as Bloch-Sulzberger syndrome (MIM 308310) is a rare, uncommon X-linked dominant inherited genodermatosis, that primarily affects female infants and is lethal in males even in the prenatal period.1,2 It is a multisystem, ectodermal and mesodermal disorder accompanied by dermatologic, dental, ocular and skeletal features due to the genetic effect. In a minority of cases, other ectodermal tissues may be affected, such as the central nervous system and also other systemic involvement can be there.1,3,4,5 This disorder is typically identified by unique skin findings, occur in a series of four stages that emerge throughout the first year of life.4

Stage 1 is known as inflammatory or vesicular stage. It is characterized by the development of papules, vesicles, and pustules on an erythematous base, distributed linearly along the lines of Blaschko. Stage 2 is known as verrucous stage and is characterized by plaques and warty papules linearly arranged over an erythematous base, also following the lines of Blaschko. Stage 3 or hyper pigmented stage is defined by the development of linear or whorled lesions, with

a brownish pigmentation, which may be accompanied by atrophy. Stage 4 is known as atrophic or hypopigmented, is characterized by areas of hypopigmentation, atrophy and absence of hair, most frequently observed on the lower extremities.1

Incontinentia pigmenti is caused by mutations in the NEMO (nuclear factor B essential modulator) gene (IKK-gamma), located in Xq28 locus. The NEMO protein is one subunit of a complex multiprotein kinase which is crucial for the activation of the transcription factor NF-kappa B, essential in the regulation of inflammatory immune and apoptotic pathways.1

Clinical findings associated with physical characteristics are enough to define the diagnosis.3

Hyperpigmentation is the typical feature of IP. The cutaneous lesions and pigmentation are usually the first manifestations and evolve through vesiculo bullous, verrucous and pigmentary stages.5

Associated findings include developmental defects of eyes (cataract, uveitis, optic atrophy, strabismus, retrolental fibroplasia), teeth (delayed dentition, partial an odontia, cone-or peg-shaped teeth,

or absence of teeth), skeletal system (skull and palatal defects), and central nervous system (epilepsy, microcephaly, mental retardation, and slow motor development).2

Cutaneous lesions may also be accompanied by defects of cutaneous appendages in the form of cicatricial alopecia or small and dystrophic nails. Lesions may be seen either at birth or before the end of first week. Rarely, skin lesions start appearing after first 2 months of birth. Brownish, bluish-grey, or slaty pigmentation in characteristically diagnostic, bizarre, splashed or ‘Chinese figure’ distribution may persist for many years.2

In the third stage has a peak onset from 3–6 months; brown to gray or blue to gray macules in streaks and whorls patterns that distribute asymmetrically on the trunk or extremities progressively fade at puberty or adulthood.5

Case Report

Twelve days female baby presented with generalized blisters, warty papules and pigmentation in whorl like pattern. The lesions followed blashkoid pattern of distribution. There were no associated ocular, dental or skeletal abnormalities. The child was born through normal vaginal term delivery and was feeding properly. She was the first child born to nonconsanguineous marriage. There is no history of similar complaints in mother or mother's parents. Histopathological examination of lesion on the right buttock revealed ballooning degeneration associated with eosinophilics pongiosis and mild dyskeratosis. It was suggestive of stage 1 (vesicular stage) of incontinentia pigmenti. The child was managed conservatively with mild topical steroids and liquid paraffin. With follow-up the vesicles healed to form pigmented papules

(papular stage). Within the next 1 year the lesions resolved to give mildly bluish pigmented macules which progressively faded. The child was majorly asymptomatic. We present this case due to its rare presentation and fewer case reports in Indian literature.

G H

J

IFigure 1 (A,B,C,D,E,F,G,H,I) : Pigmented macules and papules distributed throughout body along blaschkoid distribution (Stage 2 - Verrucous stage)

Histological Features

Histopathology from lesion on left buttock showed ballooning degeneration associated with eosinophilic spongiosis and mild dyskeratosis. There is mild upper dermal edema associated with a mild perivascular eosinophilic infiltrate. Showing Vesicular stage

Figure 3: Site of biopsy from left buttock

Figure 4 : Histopathology from lesion on left buttock showing vesicular stage (stage 1)

Diagnosis

Incontinentia pigmenti is a multi systemic disease that affects both ectodermal and mesodermal tissues.6 Diagnosis of the disease is aided by family history and history of miscarriages of male gender. IP is typically diagnosed by its cutaneous signs, which classically evolve through four stages (viz. vesicobullous, verrucous, hyper pigmented, hypo

Incontinentia Pigmenti: A Rare Case Report

Figure 2: Vesicular stage at day 5 with numerous vesicles coalescing to plaques over extremities

pigmented).7Additional alterations affect the central nervous system, eyes, teeth, mammary glands, hair, nails, and skeleton.6

Recently the diagnostic criteria were proposed for this disease and it is categorised in major criteria and minor criteria. The major criteria involve typical neonatal vesicular rash with eosinophilia, typical blaschkoid hyper pigmentation on the trunk, fading in adolescence; and linear, atrophic hairless lesions. Minor criteria include dental anomalies, alopecia, wooly hair, and abnormal nails. With a definitive family history, the presence of any major criterion strongly supports the diagnosis of incontinentia pigmenti. In the absence of a family history, the presence of at least 1 major criterion is necessary. The presence of minor criteria supports the diagnosis of incontinentia pigmenti.2

Table 1: Diagnostic Criteria for Incontinentia Pigmenti8

Discussion

Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare multi systemic X-linked dominant and uncommon genetic disorder usually affects female infants. The disease is most often characterized by an erythematous eruption with linear vesiculation that is present at birth or shortly thereafter.9,10 The hallmark sign of IP is the presence of skin lesions in affected female newborns.11 Retinal and central nervous system (CNS) impairments are rarer than skin involvement but might be severe with lifelong sequelae.9

The name of the disorder derives from the observation of incontinence of melanin from the epidermis into the dermis. The most significant medical problem in IP is blindness due to hypervascularization and consequent retinal detachment. Other manifestations include alopecia, hypodontia or anodontia, eosinophilia, nail dystrophy, and neurological complications. These medical problems, together with the skin-pigmentation abnormality, constitute the typical IP phenotype.11

IP is inherited in an X-linked dominant manner therefore, more than 95% of patients are female infants. In males, it is usually lethal and most of the affected male fetuses result in miscarriage or stillbirth. Dermatologic findings are often the first observed signs of IP and are present in nearly all patients. In most cases, the first of skin changes appear before 6 weeks of age. Progressive cutaneous manifestations are the main clinical feature of the disease and classically evolve through four stages.3

In the first stage vesicles on an erythematous base, second stage

verrucous hyper keratotic lesions, third stage hyperchromic spots and fourth stage hypochromic atrophic lesions.1

Treatment

Emollients and topical corticosteroids can be used in the first stages of the disease. Secondary bacterial infections may occur and must be treated with antibiotics.3 Treatment with topical corticosteroids or tacrolimus can delay progression of the vesicobullous stage, although the lesions resolve spontaneously.6 As neonatal herpes and incontinentia pigmenti can coexist, treatment with acyclovir must be started as soon as a viral infection is confirmed.6

Cutaneous manifestations of IP do not require specific treatment, since spontaneous resolution of the lesions usually occurs. The use of topical and systemic antibiotics for vesicular lesions is not recommended. The study by Kaya et al, 2009, relates rapid improvement in IP inflammatory lesions with the use of a combination of topical steroids: diflucortolone valerate / chlorquinaldol. Additional research is needed to clarify the therapeutic potential of topical corticosteroids in IP inflammatory lesions.1 In addition long-term and close cooperation between dermatologist, pediatrician, neurologist, genetic counselors, pathologist and the dentist is important for treatment of anomalies.5

Conclusion

Incontinentia pigmenti is a multisystemic disease with characteristic dermatological polymorphism.6,7 However, incontinentia pigmenti (IP) is a potentially serious disease because of the developmental abnormalities that affect the hair, eyes, teeth, central nervous system (CNS), and

structural development.10

IP is a single-gene disorder caused by mutations in the NEMO/IKK-y gene. The function of NEMO, a 23 kb gene consisting of 10 exons, is to permit cells to respond to external signals such as growth factors. This gene encodes a protein that regulates the function of various chemokines, cytokines and adhesion molecules, and is essential for protection against tumor necrosis factor induced apoptosis.7

When dealing with a multi systemic disorder, long-term, individualized, multidisciplinary follow-up is necessary, with evaluation by dermatologists, neurologists, ophthalmologists, and dentists, among others. Congenital hypothyroidism, myasthenia gravis, and Wilmstumor have been described in certain cases of incontinentia pigmenti.6 Longterm follow-up of IP is required since several cases of IP have been associated with cancer in childhood or ocular complications.5

References

1. Poziomczyk, Claudia Schermann; Recuero, Julia Kanaan; Bringhenti, Luana; Maria, Fernanda Diffini Santa; Campos, Carolina Wiltgen; Travi, Giovanni Marcos; Freitas, Andre Moraes; Maahs, Marcia Angelica Peter; Zen, Paulo Ricardo Gazzola; Fiegenbaum, Marilu; Almeida, Sheila Tamanini de; Bonamigo, Renan Rangel; Bau, Ana Elisa Kiszewski (2014). Incontinentia pigmenti. Anais Brasileiros de Dermatologia, 89(1), 26–36. doi:10.1590/abd18064841.20142584.

2. Gupta KD, Padhiar BB, Karia UK, Shah BJ. Case reports of incontinentia pigmenti in males. Indian J Dermatol 2013;58:328.

3. Rafatjoo R., TaghdisiKashani A. IncontinentiaPigmenti; a Rare Multisystem Disorder: Case Report of a 10-Year-Old Girl. J Dent Shiraz Univ Med Sci., 2016 September; 17(3): 233-237.

4. Greene-Roethke, Carol (2017). IncontinentiaPigmenti: A Summary Review of This Rare Ectodermal Dysplasia With Neurologic Manifestations, Including Treatment Protocols. Journal of Pediatric Health Care, (), S0891524517302663–. doi:10.1016/j.pedhc.2017.07.003

5. Motamedi MK, Lotfi A, Azizi T, Moshref M, Farhadi S. Incontinentia pigmenti. Indian J PatholMicrobiol 2010;53:302-4

6. Cammarata-Scalisi F, Fusco F, Ursini MV. Incontinencia pigmenti. https://doi. org/10.1016/j.ad.2018.10.004*

7. Shankar YU, Fatima N, Kumar MA, Prakash KS. Bloch Sulzberger syndrome (Incontinentiapigmenti): A rare case report with dental defects. J Indian Soc Pedod Prev Dent 2015;33:74-7.

8. Shankar YU, Fatima N, Kumar MA, Prakash KS. Bloch Sulzberger syndrome (Incontinentia pigmenti): A rare case report with dental defects. J Indian SocPedodPrev Dent 2015;33:74-7

9. Bodemer, C.; Diociaiuti, A.; HadjâRabia, S.; Robert, M.P.; Desguerre, I.; Manière, M.âC.; DureâMolla, M.; De Liso, P.; Federici, M.; Galeotti, A.; Fusco, F.; Fraitag, S.; Demily, C.; Taieb, C.; Valeria Ursini, M.; El Hachem, M.; Steffann, J. (2020). Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti. Journal of the European Academy of Dermatology and Venereology, 34(7), 1415–1424. doi:10.1111/jdv.16403

10. Carney RG. Incontinentia Pigmenti A World Statistical Analysis .Arch Dermatol. 1976;112(4):535-542. doi:10.1001/ archderm.1976.01630280059017

11. Aradhya S, Courtois G, Rajkovic A, Lewis RA, Levy M, Israël A, Nelson DL. Atypical forms of incontinentia pigmenti in male individuals result from mutations of a cytosine tract in exon 10 of NEMO (IKK-gamma). Am J Hum Genet. 2001 Mar;68(3):765-71. doi: 10.1086/318806. Epub 2001 Feb 8. PMID: 11179023; PMCID: PMC1274488.

Videodermoscopy Evaluation in Non-scarring Alopecia of Scalp Part-1

Dr. Palak Garg

MD (DVL)

Consultant Dermatologist

Dr. Talwar's Skin, Hair and Laser Clinic Chandigarh, India

Dr. Gaurav Rajauria

PharmD (Doctor of Pharmacy)

Assistant Professor Department of Pharmacy Dr. Bhimrao Ambedkar University, Chhalesar Agra, Uttar Pradesh, India

Abstract Introduction

Hair is a versatile structure and great importance has been linked to it in beautification of human being since ages. Studies have specifically addressed the psychological impact of androgenetic alopecia (AGA) in men have shown that men with visible hair loss are perceived as older, weaker and less physically attractive than their non balding counterparts. Hair loss in women gives significant stress and lowers self confidence.

Aim

To perform videodermoscopic findings in non-scarring alopecia of scalp verses control volunteers.

Material & Methods

A total of 140 cases satisfying the inclusion criteria were screened for general physical examination and scalp examination including hair shaft and root, and tests for hair anchorage and fragility were also

done. The lesions were examined through videodermoscope, photographs were taken, and findings were documented.

Results

The mean age of the patients (46 males and 20 females) was 26.85 years. The mean age of onset was 25.15 years. The mean duration of alopecia was 10.3 months. Most common AA in our study was patchy type (57/66, 87.7%).

Conclusion

Videodermoscopy is an effective non-invasive tool of considerable potential in dermatological practice. It is gaining popularity as an accessory tool in differential diagnosis of hair loss.

Key words: Androgenetic alopecia, non-scarring, videodermoscopy, perifollicular, hair fall.

Introduction

Hair is a versatile structure and great importance has been linked

Videodermoscopy

to it in beautification of human being since ages. Hair forms a vital element of an individual’s physical appearance and changes in the hair including its loss can have correspondingly profound effects on the inter-personal relations and self image. Studies have specifically addressed the psychological impact of androgenetic alopecia (AGA) in men have shown that men with visible hair loss are perceived as older, weaker and less physically attractive than their non balding counterparts.[1,2] Hair loss in women gives significant stress and lowers self confidence. Which incites them do try many different hair care products without the knowing the primary cause, giving stimulus to the booming cosmetic products industry.[3]

At present simple and reliable procedures have not been developed to get a clearer bigger picture of hair loss, which should be patient friendly, pain less and reproducible. Until now, most of the hair and scalp conditions were examined and treated based on naked eye clinical examination and hand held magnifier of 4X magnification with improper lighting which was subjective and based on skill of the clinician. The findings were mostly not recorded in digital media hence was not reproducible. This compromised on follow up and further management of the patients. [4,5]

The only gold standard for diagnosis of hair loss disorders is scalp biopsy, which is painful and usually not accepted by patients. Scalp biopsy being one of the modalities of investigation, is an invasive procedure which requires a minor operation theatre set up and histopathology reading. The drawbacks included being invasive, unable to study the entire scalp

and reduced patient compliance for a repeat biopsy. Unfortunately, pathologic findings also are not reliably diagnostic. In males with established AGA, the characteristic patterns are easily discernible, however, especially in women the clinician is often challenged by patients with initial stages of AGA where hair loss is reported but alopecia is not recognizable or effects of treatment are hard to measure. Consequently there is a need for a sensitive tool to monitor hair loss and treatment responses. [6,7]

Over the last decade innovations in technology have been progressively growing in the field of medicine. This has facilitated the understanding of pathophysiology of a disease. Accordingly an attempt has been made to shed some light on the field of trichology, one still hampered by areas of darkness, with help of modern technology.[8,9]

With the increasing awareness about the cosmetology treatments available among patients and media available for information, a need to upgrade the non invasive investigative tools has arrived for better understanding and appropriate treatment for hair loss disorders.[10]

Videodermoscopy is a tool which aids in diagnosis and management of hair and scalp disorders. Videodermoscopy is medical equipment which can magnify scalp and hair images from 20X to 100X or more in a live demonstration over the computer monitor which shows different patterns and findings in hair and scalp disorders which can be recorded, stored, transferred and reproduced for evaluation and follow up. It can be repeated as and when required as a simple OPD based procedure which aids in accurately diagnosing hair and

scalp conditions.[11,12]

As most of the studies and published articles available are based on a western population a study is required in Indian patients. Further this study will differentiate findings from the normal scalp to abnormal ones.

Aim & objectives

To perform videodermoscopic findings in non-scarring alopecia of scalp verses control volunteers.

Material & Methods

This study of videodermoscopy findings in non-scaring alopecia of scalp verses control volunteers in a tertiary set up’ was carried out in the outpatient department of dermatology and venereology in a private teaching hospital from January 2020 to June 2021.

The study includes a total of 140 cases of androgenetic alopecia, alopecia areata, telogen effluvium and 40 controls. Scarring alopecia will be excluded from the study by history, clinical examination and scalp biopsy for histopathological examination as and when required. A videodermoscope of 50x magnification with a LED light and connectable to the computer hard disk drive with a USB cable through which videodermoscopic pictures can be recorded was used. Each case and control included in the study was subjected to a detailed history taking for hair loss, medical illness and treatment history taking and examination with a videodermoscope was done following consent. Hair pull test was performed. Information was recorded on a proforma and clicked pictures from the videodermoscope was analyzed for findings and attached to the digital profile created on Microsoft word document of the patient on computer.

Statistical analysis

All statistical analysis were performed using SPSS version 13 for windows. Descriptive statistics (n, minimum, maximum, mean, median, mode, standard deviation) outlined the variables used within the study. IQR= Interquartile Range (i.e. 75th Percentile-25th Percentile) Kruskal-Wallis One Way Analysis of Variance on Ranks applied as data failed 'Normality' test for one of the variable tables. A cross tabulation with Pearson [chi]2 test was used to measure differences in two categorical variables between two groups, for example, case and control Analysis of variance is used to test the equality of means for continuous variables between more than two groups. p – value of 0.05 was considered significant.

Sample size calculation

Sample size was estimated by using the proportion alopecia (common cause) of nonscarring alopecia's detected by videodermoscopy Resuts & Discussion

“Hair” is the crowning glory of human body and its symbolic and psychosocial importance can be estimated by the large number of patients who present in dermatology clinics with complaints of hair loss. The departure from accepted cultural norms regarding this cosmetic asset leads to much distress and industrial activity.

The mean age of the patients (46 males and 20 females) was 26.85 years. The mean age of onset was 25.15 years. The mean duration of alopecia was 10.3 months. Most common AA in our study was patchy type (57/66, 87.7%). Single patch was seen in 24 patients and multiple patches in 33 patients. Diffuse AA was seen in five patients. Ophiasis and alopecia universalis were seen in two patients each. Nail changes were fine pitting (4), ridging (2), thinning of nail plate (2). Twenty nail dystrophy, distal onycholysis, striate leukonychia and coarse pitting were seen in one patient each. The most common dermoscopic finding was yellow dots seen in 54 patients (81.8%), followed by black dots (44 patients, 66.6%), broken hairs (36 patients, 55.4%), short vellus hair (27 patients, 40.9%) and tapering hairs (8 patients, 12.1%).

in two patients each. Nail changes were fine pitting (4), ridging (2), thinning of nail plate (2). Twenty nail dystrophy, distal onycholysis, striate leukonychia and coarse pitting were seen in one patient each. The most common dermoscopic finding was yellow dots seen in 54 patients (81.8%), followed by black dots (44 patients, 66.6%), broken hairs (36 patients, 55.4%), short vellus hair (27 patients, 40.9%) and tapering hairs (8 patients, 12.1%).

Table 1: Distribution among the cases of conditions

Conditions No. Percentage

Alopecia areata 30 21.4% Androgenetic alopecia 40 28.6% Telogen effluvium 30 21.4% Control 40 28.6% Total 140 100.0%

Table 2: Association of age(yrs) among the cases between- Alopecia areata, Androgenetic alopecia and Telogen effluvium groups

Alopecia

effluvium No. 7 13 7 1 2 30

% 26.7% 33.3% 30.0% 10.0% 0.0% 100.0%

Androgenetic alopecia No. 13 17 3 6 1 40

% 32.5% 42.5% 7.5% 15.0% 2.5% 100.0%

Telogen effluvium No. 7 13 7 1 2 30 % 23.3% 43.3% 23.3% 3.3% 6.7% 100.0%

Total No. 28 40 19 10 3 100 % 28.0% 40.0% 19.0% 10.0% 3.0% 100.0%

Chi-Square tests Value df p-value Association is-

Pearson ChiSquare $ 10.623 8 0.224 Not significant

Pearson ChiSquare ^ 2.25 4 0.690 Not significant

$ 6 cells (40.0%) have expected count less than 5. ^ Column data pooled and Chi-Square Test reapplied.

Table 3: Statistics of various variables in Control cases

Control No. Mean SD Median IQR Minimum Maximum Age (years) 40 30.55 9.66 30.00 14.50 18.00 58.00

Variables

Table 4: Sex distribution among the cases between- Alopecia areata, Androgenetic alopecia and Telogen effluvium groups

Condition Sex Total Female Male

Alopecia areata No. 17 13 30 % 56.7% 43.3% 100.0%

Androgenetic alopecia No. 21 19 40 % 52.5% 47.5% 100.0%

Telogen effluvium No. 25 5 30 % 83.3% 16.7% 100.0% Total No. 63 37 100 % 63.0% 37.0% 100.0%

% 52.5% 47.5% 100.0%

Telogen effluvium No. 25 5 30 % 83.3% 16.7% 100.0%

Total No. 63 37 100 % 63.0% 37.0% 100.0%

Controls No. 25 15 40 % 62.5% 37.5% 100%

Chi-Square tests Value df p-value Association is-

Pearson ChiSquare 7.729 2 0.021 Significant

Table 5: Association of Type of Hair Loss among the cases between- Alopecia areata, Androgenetic alopecia and Telogen effluvium groups

Condition Type of Hair Loss Total Diffuse Localised

Alopecia areata No. 3 27 30 % 10.0% 90.0% 100.0% Androgenetic alopecia No. 40 0 40 % 100.0% 0.0% 100.0%

Telogen effluvium No. 30 0 30 % 100.0% 0.0% 100.0% Total No. 73 27 100 % 73.0% 27.0% 100.0%

Chi-Square tests Value df p-value Association is-

Pearson ChiSquare 86.301 2 1.82E-19 Significant

Videodermoscopy Evaluation in Non-scarring Alopecia of Scalp Part-1

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of interest.

References

1.Ohyama M. Management of hair loss diseases. Dermatologica Sinica.2010 28; 139–145

2.Van neste, d. female patients complaining about hair loss: documentation of defective scalp hair dynamicswith contrast-enhanced phototrichogram. Skin res technol. 12, 83-88 (2006)

3. Inui S. Trichoscopy for common hair loss diseases: algorithmic method for diagnosis. J Dermatol. 2011 Jan; 38(1): 71-5.

4. Kossard S, Zagarella S. Spotted cicatricial a lopecia in dark skin:a clue to fibrous tracts. Australas J Dermatol 1993;34:49-51.

5. Strumia R, Califano A. Le molteplici applicazioni dermato logichedella video- microscopia a sondaottica. G Ital Dermatol Venereol 1996;131:397-402

6. Tosti A, Duque-Estrada B. Dermoscopy in Hair Disorders. J Egypt Women Dermatol Soc 2010; 7: 1-4.

7. D’AmicoD,Vaccaro M, Guarneri F, Borgia F, Cannavo SP, Guarneri B. Phototrichogram using videomicroscopy: a useful technique in the evaluation of scalp hair. Eur J Dermatol 2001;11:17-20.

8. De Lacharrie`re O, Deloche C, Misciali C, et al. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch Dermatol 2001; 137:641-6.

9. Hoffmann R. TrichoScan: combining epilumine scence microscopy with digital image analysis for the measurement of hair growth in vivo. Eur J Dermatol 2001; 11:362-8.

10. Micali G, Lacarrubba F. Possible applications of videodermoscopy beyond pigmented lesions. Int J

Dermatol 2003;42: 430-3.

11. Lacarrubba F, Dall’Oglio F, Nasca MR, Micali G. Videodermoscopy enhances diagnostic capability in some forms of hair loss. Am J ClinDermatol 2004;5:205-8.

12. Deloche C, de Lacharrie`re O, Misciali C, Piraccini BM, VincenziC, Bastien P, et al. Histologic features of peripilar signs associated with androgenetic alopecia. Arch Dermatol Res 2004;295:422-8.

Videodermoscopy Evaluation in Non-scarring Alopecia of Scalp Part-1

Ritlecitinib yields high repigmentation rates in nonsegmental vitiligo

Vitiligo is a common acquired skin disorder which results from the loss of melanocytes from the epidermis and clinically manifests as well-demarcated white patches on the body. It is a common and easily recognized disorder for all dermatologists. It has an unpredictable clinical course and the treatment goals for vitiligo include arresting progression, repigmentation of existing lesions, and maintenance of repigmentation. Treatment options for vitiligo are limited and often require lengthy treatment and have limited efficacy.

Ritlecitinib significantly out-performed placebo across various doses in safety and efficacy for the treatment of nonsegmental vitiligo, according to a recent clinical trial.The phase 2b, randomized, doubleblind, multicenter study analyzed the efficacy and safety of ritlecitinib, an inhibitor of Janus kinase 3, in the treatment of 364 patients with nonsegmental vitiligo. Eligible patients were aged 18 to 65 years with a clinical diagnosis of nonsegmental vitiligo for at least 3 months and body surface area involvement of 4% to 50%.

Patients were randomly assigned to one of six groups. Two groups received a loading dose of ritlecitinib 100 mg or 200 mg daily for 4 weeks followed by 50 mg daily for 20 weeks. Four groups without a loading dose received ritlecitinib 50 mg, 30 mg or 10 mg or matching placebo daily for 24 weeks. Also, 187 patients were assigned to treatment in a blinded 200 mg/50 mg ritlecitinib group for a 24-week extension period based on response at week 16.

The researchers observed significant differences vs. placebo for the primary efficacy endpoint, which was the percent change from baseline in Facial-Vitiligo Area Scoring Index at week 24, in the 50 mg groups with (–21.2 vs. 2.1; P < .001) or without a loading dose (–18.5 vs. 2.1; P < .001), as well as in the 30 mg group (–14.6 vs. 2.1; P = .01). Researchers also observed accelerated improvement among all patients during the extension period.

Across the 48-week treatment, no dose-dependent adverse events were observed. This phase 2 trial suggests ritlecitinib is an effective and well tolerated treatment for patients with active [nonsegmental vitiligo]. As indicated by data during the extension period, longer treatment duration may be required for optimal repigmentation.

Smoking, obesity-related factors significantly increase psoriasis risk

Psoriasis is an immune-mediated disease that causes inflammation in the body. It is one of the most frequent chronic inflammatory skin diseases. The prevalence of psoriasis varies with the country, and psoriasis can appear at any age suggesting that ethnicity, genetic background, and environmental factors affect the onset of psoriasis.

According to recent study, smoking and obesity-related factors are significantly associated with an increased risk for psoriasis. Using a two-sample mendelian randomization (MR) analysis, researcher’s team investigated the causality between several potentially modifiable factors and the risk of psoriasis. The researchers used the random-effects inverse variance-weighted (IVW) method in their statistical analysis.

The researchers evaluated risk factors from the largest genome-wide association study meta-analysis including data from 19,032 cases of dermatologist-diagnosed psoriasis and 286,226 controls from eight different cohorts.Results found that genetically predicted smoking initiation (ORMR-IVW = 1.51; 95% CI, 1.3- 1.74) and higher lifetime smoking index (ORMR-IVW = 2.11; 95% CI, 1.21-3.5) were associated with increased odds of psoriasis. Additionally, high associations with psoriasis were found for increased hip (ORMR-IVW = 1.55; 95% CI, 1.15-2.07) and waist circumference (ORMR-IVW = 1.86; 95% CI 1.31 to 2.64). Increased childhood (ORMR-IVW = 1.4; 95% CI, 1.14-1.71) and adult BMI (ORMR-IVW = 1.63; 95% CI, 1.32-2) were significantly associated with a higher risk of psoriasis as well. However, after adjusting for adult BMI in multivariable analysis, the direct effect of childhood BMI was not significant.In contrast, higher sleep duration was associated with decreased risk of psoriasis (ORMR-IVW = 0.56; 95% CI, 0.37-0.84) as was increased years of education (ORMR-IVW = 0.78; 95% CI, 0.62-0.98), the latter persisting after adjusting for genetic predictors of smoking and adult BMI.

The results of this study established a causal role of specific lifestyle and obesity-related factors in psoriasis risk, all of which are modifiable, researcher wrote. Targeting these risk factors represents an opportunity to simultaneously reduce the risk of multiple distinct disease processes and thus ease the burden of multi-morbidity on individual’s health system.

Infants, young children finally get relief from eczema's terrible itch

Eczema, also known as atopic dermatitis, is a chronic inflammatory skin disorder characterized by red, dry, often oozing skin and itch that can profoundly affect the lives of affected patients and their families. The first study to treat moderate-to-severe eczema in infants and children 6 months to 5 years old with a biologic drug (monoclonal antibody) rather than immune-suppressing medications shows the drug was highly effective in reducing the signs and symptoms of moderate-to-severe eczema. More than half of children had at least a 75% reduction in signs of eczema and itch. Kids slept through night for first time instead of scratching. Parents saw children's personalities change as they were able to lead a normal life, report researchers involved in a new multisite phase III study.

During the past few years, dupilumab isa new medication which is the first "biologic" drug to treat eczema in a targeted manner, meaning a narrow attack on just what scientists have found is causing the manifestations of the disease in skin. This medication was found to be effective and safe in studies with adults, then adolescents, then other school-aged children. A 16-week course of dupilumab, a medication that targets a key immune pathway in allergies, resulted in more than half the children having at least a 75% reduction in signs of eczema and highly significant reductions in itch with improved sleep. This is the first large-scale, randomized, placebo-controlled trial of a monoclonal antibody in any skin disease, including eczema, in children as young as 6 months. Preschoolers who are constantly scratching, awake multiple times a night with their parents, irritable and markedly curtailed in their ability to do what other children their ages can do improved to the extent that they sleep through the night, change their personalities and have a normal life as babies and children should, researcher said.

The ability to take this dupilumabwill significantly improve the quality of life for infants and young children who suffer tremendously with this disease. As a result of this study, this medication is now available to infants and preschoolers as young as 6 months of age. It has "an outstanding safety profile" and does not even require any laboratory tests before starting the medication, researcher said. As a result of the study, scientists and physicians can start to better understand the relationships between eczema and a variety of allergic disorders and can consider the possibility of using this medication for other disorders that affect these very young children.

Sensory Neurons in Human Skin Play Key Role in Pigmentation

Our skin forms the physical boundary between us and the outside world, yet it still holds a surprising number of secrets. Now, researchers have discovered that sensory nerve cells in our skin do more than just help us feel our way around.A research group has found that sensory neurons play an important role in human skin pigmentation and physiology. Specifically, the neurons secrete a protein known as Repulsive Guidance Molecule B (RGMB), which stimulates melanocytes. This study could lead to the development of new drugs to treat pigmentation disorders.

A researchrevealed that sensory neurons in human skin play an important role in pigmentation. Pigmentation in our skin is caused in part by a group of substances known as melanin, which are produced by skin cells called melanocytes. When melanocytes are damaged or reduced in number, this leads to either increased or limited melanin production, resulting in pigmentation disorders. The researchers explored the relationship between sensory neurons and melanocytes, and found that there was a greater degree of contact between them in skin color patch tissue than control tissue. When cultured with neurons, melanocytes were also found to have higher pigmentation and an increased survival rate. Melanocytes cultured in growth media that had been conditioned with sensory neurons showed increased survival, as well as longer dendrites, these effects were specific to melanocytes. Additionally, researchers identified proteins secreted by sensory neurons, including Repulsive Guidance Molecule B (RGMB). They discovered that melanocyte survival and darkness is promoted by RGMB.

The study revealed that sensory neurons play a role in modulating a number of features of human melanocytes via the secretion of RGMB, which is a key factor that stimulates melanocytes. The study results highlight how important sensory neurons are to skin pigmentation and physiology.The results of this study could lead to the development of new drugs for use with current therapies by enabling the discovery of previously unknown molecules and mechanisms that include RGMB.