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COMPARATIVE EFFICACY OF KLIGMAN’S REGIMEN OVER OTHER TOPICAL THERAPIES IN TREATMENT OF MELASMAVishal Wali1,Suma Patil2, S. K. Patil3, A.S. Hogade4, N. S. Manthale5, P.S. Sagare6

HOW TO CITE THIS ARTICLE: Vishal Wali, Suma Patil, S. K. Patil, A.S. Hogade, N. S. Manthale, P.S. Sagare. “Comparative Efficacy OfKligman’s Regimen Over Other Topical Therapies In Treatment Of Melasma”.Journal of Evolution of Medical and Dental Sciences 2013; Vol. 2, Issue 51, December 23; Page: 9856-9867.

ABSTRACT: BACKGROUND: Melasma is an acquired, symmetrical, circumscribed facial pigmentary disorder seen among females with significant psychological and social impact which is often recalcitrant to treatment.OBJECTIVES:This study mainly focus on efficacy of combination regimen (kligman’s) over other routinely used topical therapies.METHOD: A total of 100 patients with facial melasma attending the OPD of Dermatology,Venereology and Leprosy BTGH M.R MEDICAL COLLEGE,Gulbarga were studied.Patients were divided into 5 groups of 20 each and each group received different treatment. Group-A Combination, Group-B Glycolic/TCA peel, Group-C Hydroquinone, Group-D Kojic Acid, Group-E Azelaic acid and they were advised to apply the cream every night and were followed up at 3rd,6th and 9th week. At each visit clinical response to treatment was calculated and side effects were noted at each visit.RESULTS: At the end of 9 weeks there was significant improvement in patients treated with combination of steroid +RA+HQ and considerable improvement was seen in other regimens also but less compared to combination cream.CONCLUSION: The results of the study show that combination cream is better topical hypopigmenting agent when compared to other topical therapies alone.KEYWORDS:Melasma, Kligman’s regimen, Hyperpigmentation.

INTRODUCTION: Melasma is one of the most common causes of acquired, symmetric hypermelanosis of the face. It is characterized by tan-brown macules and patches with a predilection for areas of the skin exposed to the sun, in particular the cheeks, forehead, upper lip, nose, and chin. Women are more affected than men (female to male ratio, 9:1) 1. It is a psychologically stressful condition for the modern men and women who are cosmetically conscious. Because melasma is a facial disfigurement, it is emotionally devastating to affected individuals as well as a source of social prejudice in many cultures. A study conducted to determine the effect of melasma on health-related quality of life reported that social interactions, recreation, and emotional well-being were adversely affected by the condition.

The disease is more common among the women of child bearing age, although men also suffer from this condition and account for about 10% of the cases. Melasma affects all racial groups. But it is more prevalent among the dark skinned people (Fitzpatrick skin types IV to VI), especially in women of Hispanic, Caribbean and Asian origin who live in areas with intense ultraviolet radiation. The exact incidence of melasma is unknown.

Although the precise cause of melasma is not known, multiple factors have been implicated in the etiopathogenesis of this condition. These include genetic factors, exposure to UV radiation, pregnancy, oral contraceptives, estrogen-progesterone therapies, thyroid dysfunctions, usage of cosmetics and antiepileptic drugs. There are three clinical patterns- centrofacial, malar and

Journal of Evolution of Medical and Dental Sciences/Volume 2/Issue 51/December 23, 2013 Page 9856

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mandibular, depending upon the site of affection. Melasma is often a therapeutically challenging disease and current treatments include topical hypopigmenting agents, chemical peels and lasers.

REVIEW OF LITERATURE: The term “Melasma” is derived from the greek word “Melas” meaning “Black”and “Chloasma” from the greek word “Chloazein” meaning “to be green”.2 It is one ofthe most common cause of acquired hyperpigmentation, presents as irregular brownmacules on sun-exposed skin. The most common sites of involvement are the cheeks,forehead, upper lip, nose,chin and V area of the neck, rarely in the neck and forearms.The large, spreading, pigmented macules often have polycyclic or arciform borders.Pigmentation may be guttate, confetti-like pigmented macules, linear, or in largecircular macules.3

Historical Aspects: The term melasma has been used to describe the various types of melanodermatous conditions. Initially the term chloasma had been employed at one time to describe practically all melanodermatous conditions and this included even condition like tineaversicolor.

The application of the term chloasma to fit into the description of mild hyperpigmentation of the face of a mottled nature in which no epidermal or dermal changes are evident, except for the hyperpigmentation was first made by Beeker SW. The term chloasma literally means “green spot” to describe the characteristic colored pigmentation4. Chloasma is derived from the Greek word chloazein, meaning "to be green." Melas, also Greek means "black." Since the pigmentation is never green in appearance, melasma is the preferred term5.

The term melasma which literally means “black spot” was initially employed to describe the pigmentation of a very dark color4.

Melasma is sometimes used interchangeably with the term “chloasma”, which is a hyperpigmentation that often results from pregnancy or changes in uterine and ovarian hormones6.Because of its characteristic relation with pregnancy it was also called as “mask of pregnancy”7.

Distribution and incidence: The exact incidence of melasma is unknown8.Melasma affects all racial groups but it is more prevalent in dark skinned people (skin types

IV to VI) especially in women of Hispanic, Asian and African Americans origin including Indians who live in areas with intense UV radiation9.Sex: The disease is most commonly observed in women: men represent only 10%10.Age: It is most common in second and fifth decade of life11 and in women of child bearing age12.Seasonal variation: Studies have shown that it worsens in summer and improves during winter season13.Sunlight: There is a high incidence of melasma in Asian and Africans who are exposed to high UV radiation14.Ultraviolet radiation15-21 :For medical photobiology, the UV range (200 to 400 nm) is subdivided into UVA, UVB and UVC14.


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UV radiation causes peroxidation of cell membrane lipids, leading to generation of toxic free radical, which are called lipoperoxides. This probably stimulates melanocytes to increase melanin production and thus hyperpigmentation.

Female hormones:Melasma occurs frequently during pregnancy and menopause22. High oestrogen and progesterone levels have been implicated in causing melasma, use of oral contraceptives, diethyl stilbestrol administration and hormonal replacement therapy in postmenopausal women23. Melasma of pregnancy usually clears within few months of delivery.Genetic Factors:More than 30% of patients have a family history of melasma.Other factors incriminated in the pathogenesis of melasma include thyroid dysfunction, cosmetics, and phototoxic and antiseizure drugs24.Idiopathic: In spite of the so many etiological factors listed have been studied in detail, it is estimated that nearly 1/3 to1/5cases no exact etiological factors could be identified 25.

HYPERPIGMENTATION AND QUALITY OF LIFE: Melasma can have a severe impact on the quality of life by undermining a patient’s psychological and emotional well-being. Disfiguring facial lesions can lead to decreased social functioning, lowered productivity at work or school and reduced self-esteem26.Clinical Features: Melasma is a common pigmentary disorder characterized by development of slowly enlarging tan-brown macules and patches3. The large, spreading, pigmented macules often have polycyclic or arciform borders. The pigmentation may be guttate in confetti-like pigmented macules, linear or in large circular macules27.

The most common sites of involvement are the cheeks, fore head, upper lip, nose and chin (Sun exposed). Other sites like forearm and neck may also be involved in any of these patterns28.

TYPES:Three patterns of melasma are recognized clinically: centrofacial (most common), malar, and mandibular.

Based on wood’s light (wavelength, 340-400nm) examination of the skin, melasma can be divided into four types- The epidermal type, Dermal Melasma, Mixed variety, Indeterminate type.22

Differential Diagnoses29: Acquired bilateral nevus of Ota-like macules, Argyria, Addison’s disease, Atopic dermatitis,Berloque dermatitis ,Chronic actinic dermatitis, Chrysiasis ,Contact


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dermatitis,Cutaneous lupus erythematosus, Drug-induced hyperpigmentation, Erythema dyschromicumperstans, Erythromelanosisfollicularisfaciei et colli, Exogenous ochronosis, Facial erythema abigne, Lentigo, Lichen planus, actinic type,Mastocytosis, Minocycline pigmentation, Photosensitivity reactions, Polymorphous light eruption, Poikiloderma of Civatte,Postinflammatory hyperpigmentation, Riehl’smelanosis, Skin infections

HISTOPATHOLOGY: Melanin is increased in the epidermis, in the dermis, or (most commonly) in both locations. Epidermal melanin is found in keratinocytes in the basal and suprabasal area. In most cases, the number of melanocytes is not increased, yet the melanocytes that are present are larger, more dendritic, and more active. Dermal melanin is found in the superficial and mid dermis within macrophages, which often congregate around small, dilated vessels. Inflammation is sparse or absent30.

TREATMENT: The reasons why patients seek medical advice may be psychologic and superstitious. They feel embarrassed by their appearance, and social contact becomes distressing31.Principles/aims of therapy: The principles/aims of therapy include the following.

1. Protection from sunlight.2. Inhibition of the activity of melanocytes.3. Inhibition of the synthesis of melanin.4. Removal of melanin.5. Disruption of melanin granules31.

MATERIALS AND METHODSSource of Data:A prospective study was carried out on 100 patients presenting with melasma.

Data was collected from 100 patients with facial melasmaInclusion criteria

Patients attending skin OPDAll the age groupsBoth sexes

Exclusion criteriaPost inflammatory hyperpigmentationOther pigmentarty disordersPatients already on treatment.

A detailed history was elicited with reference to duration, onset, progression, family history, obstetric history, cosmetic history and previous treatment. Wood’s lamp examination was done. After making diagnosis of melasma the patients were classified according to the clinical features. All patients were informed regarding the nature of disease, course, prognosis and the probable adverse effects of treatment modalities.

After taking consent from the patients, the following regimens were followed. By random number method of Randomization, Patients were allocated into 5 different groups / regimens. Each group / Regimens consists of 20 patients.Regimen –I: 20 patients were taken in this group


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They were advised sunscreen in the morning and a combination of retinoic acid + HQ + fluorinated steroid at night (KLIGMAN’s regime)Regimen –II: 20 patients were taken in this group

They were selected for chemical peel i.e. with glycolic acid and TCA. All were advised sun screen in morning. During the peel programme after taking necessary precautions, patients were advised to wash his/her face with soap and water. The face was then cleaned with spirit. Then one coating of acetone was applied (in required concentrations) starting from forehead – right cheek-chin-left cheek, nasal bridge – nose – perioral area - upper and lower eyelids. The glycolic acid was applied for a particular time period i.e. 30 seconds, 1 minute, 1 ½ minutes and 2 minutes in different concentrations. For tricholoracetic acid all the above procedure was same except that TCA was applied till frosting was seen. Than his/her face is cleaned with ice water for termination and neutralization.Regimen-III: 20 patients in this group were advised to use sun screen in the morning and HQ cream at night.Regimen –IV: 20 patients in this group and were advised to use sunscreen in morning and KOJIC ACID at night.Regimen-V: 20 patients in the group and were advised to use sunscreen in morning and Azelaic acid cream at night.

All patients were followed up at 3,6 and 9 weeks during every visit, the results were graded as follows.

Grade-I: Slight improvement, barely noticeable (<25%)Grade-II: Moderate improvement, noticeable (25.50%)Grade-III: Obvious improvement (50-75%)Grade-IV: Very marked improvement (>75%)

RESULTS:

Grade Number of Patients PercentageGrade I 8 40%Grade II 9 45%Grade III

2 10%

Grade IV 1 05%Total 20 100%

Table 2: Efficacy of Regimen II


Grade Number of Patients PercentageGrade I 4 20%Grade II 5 25%Grade III

6 30%

Grade IV 5 25%Total 20 100%

Table 1: Efficacy of Regimen I (Combination cream)

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(Glycolic/TCA peel)

Grade Number ofPatients PercentageGrade I 9 45%Grade II 8 40%Grade III 2 10%Grade IV 1 05%

Total 20 100%

Table 3: Efficacy of Regimen III (Hydroquinone)

Grade Number of Patients PercentageGrade I 8 40%Grade II 7 35%Grade

III4 20%

Grade IV 1 05%Total 20 100%Table 4: Efficacy of Regimen IV (Kojic acid)

Grade Number of Patients PercentageGrade I 8 40%Grade II 8 40%Grade

III3 15%

Grade IV 1 05%Total 20 100%Table 5: Efficacy of Regimen V (Azelaic acid)

GradeRegimen I Regimen II Regimen III Regimen IV Regimen V

No. of patients

%No. of

patients%

No. of patients

%No. of

patients%

No. of patients

%

Grade I 4 20 8 40 9 45 8 40 8 40Grade II 5 25 9 45 8 40 7 35 8 40Grade III 6 30 2 10 2 10 4 0 3 15Grade IV 5 25 1 5 1 5 1 5 1 5

Total 20 100 20 100 20 100 20 100 20 100

Table 6: Efficacy of Kligman over other modalities of treatment

Comparing regimen I with Regimen IIX2=6.31 p<0.05 significantRegimen I and Regimen IIIX2=6.20 p<0.05 significant


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Regimen I and Regimen IVX2=6.02, p<0.05, significant

Regimen I and Regimen VX2=6.12, p<0.05, significantRegimen II and III

X2=1.18 p>0.05 not significantRegimen II and IV

X2=1.94 p>0.05 not significantRegimen III and IV

X2=2.10 p>0.05 not significantRegimen III and V

X2=1.98 p>0.05 not significantRegimen IV and V

X2=1.08 p>0.05 not significant

CONCLUSION: In present study of 100 patients higher incidence was in 21-30 years age group and females predominate with malar pattern being commonest.

There was significant improvement in patients treated with combination of steroid + Retinoic acid + HQ (Kligman’s regimen)

Considerable improvement was seen in other regimens also but was less compared to the combination cream.

From above all observation indicates that melasma in a common disease in reproductive age group. Commonly seen during pregnancy and the condition has variable type of response to different modalities. Thus even today the treatment of melasma seems to be limited even though there are many modalities of treatment.


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BIBLIOGRAPHY: 1. Guevara IL, Pandya AG. Safety and efficacy of 4% hydroquinone combined with 10% glycolic

acid, antioxidants, and sunscreen in the treatment of Melasma. Int J Dermatol 2003;42: 966-972.

2. Thapa DM. Melasma (chloasma): A review with current treatment options. Indian J Dermatol 2004;49(4): 165-176.

3. Pandya AG, Guevara IL. Disorders of hyperpigmentation. DermatolClin 2000;18: 91-8.4. Newcomer VD, et al. A melanosis of the face (Chloasma). Arch Dermatol. 1961; 63:284-79.5. http://emedicine medscape.com/article/10686-40-overview.


http://emedicine/

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6. Aditya K, Gupta MD, Susan Taylor, et al. The treatment of melasma. A review of clinical trial. J Am AcadDermatol. 2006; 55: 1048-65.

7. Bruke KE. Facial wrinkles, prevention and nonsurgical correction. Post Grad Med 1990; 88: 207.

8. Grimes PE; Melasma Etiologic and therapeutic considerations. Arch Dermatol 1995 Dec; 131(12):1453-7.

9. Taylor SC. Epidemiology of skin diseases in people of dark color. Cutis. 2003; 71: 271-5.10. Vazquez M, Maldonaldo H, Benaman G Sanchez. Melasma in men: A clinical and histological

study. Int J Dermatol 1988; 27: 25-7.11. Enzoberodesco, Marco Ardigo, Marta Beradesco, Norma Cameli. Melasma: Current and future

treatments. Expert Rev, Dermatol 2008; 3(2): 187-93.12. Lawley TJ, Yancef KB. Skin changes and diseases in pregnancy. In: Freeberg IM, Eisen, Wolf K,

et al. eds Dermatology in General Medicine, 5th Ed. New York: McGraw Hill. 1999, 1963-69.13. Urabe K Nakayama, J Hon. Mixed epidermal and dermal hypermelanosis. Nordlund JJ, Boissy

RE, Hearing VJ, King RA, Ortonne JP, editors. The pigmentary system: physiology and pathology. New York: Oxford university press; 1998. pp 909-13.

14. Pathak MA, Fitzpatrick TB, Kraun EW. Usefulness of retinoic acid treatment of melasma. J Am AcadDermatol. 1981; 4:698-7 10.

15. Girotti AW: Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 1998; 39:1529.

16. Geiger PG et al: Lipid peroxidation in photodynamically stressed mammalian cells: use of cholesterol hydroperoxides as mechanistic reporters. Free RadicBiol Med 1997; 23:57.

17. Cadet 3 et al: Effects of UV and visible radiations on cellular DNA. Cuff ProbiDermatol 2001;29:62.

18. Moor AC, Gasparro FP: Biochemical aspects of psoralenphotochemotherapy. ClinDermatol 1996; 14:353.

19. Katiyar SK. A single physiologic dose of ultraviolet light exposure human skin in vivo induces phosphorylation of epidermal growth factor receptor. Int. J Oncol 2001; 19:459.

20. Wan YS et al. Ultraviolet irradiation activates PI3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int. J Oncol 2001; 18:461.

21. Nicolaidou E, Antoniou C, Katsambas AD. Origin, clinical presentation, and diagnosis of facial hypermelanoses. DermatolClin 25 (2007) 32 1-326.

22. Johnston GA, Sviland L, McLelland J. Melasma of the arms associated with hormone replacement therapy [letter). Br J Dermatol 1998; 139: 932.

23. Lutfi. RJ et al. Association of Melasma with thyroid autoimmunity and other thyroidal abnormalities and their relationship to the origin of Melasma. J ClinEndocrinolMetab 1985;61 :28.

24. Hassan, Kaur, Sally R, Dase RI. Hormonal milieu in melasma in fertile women. J Dermatol 1998; 25(8): 501-2.

25. Balakrishnan R Improved quality of life with effective treatment of facial melasma: the PIGMENT, J of Drugs in Dermatol. Jul-Aug 2004.

26. Amit G Pandya, MD, Ian L Guevara, MD. Disorders of pigmentation. Dermatolclin. 2000;18:1.


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27. Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne JP, editors. The pigmentary system: physiology and pathology. New York: Oxford university press; 1998. 909-13.

28. http://emedicine medscape.com/article/10686-40-followup.29. http://www.ijdvl.com/article.asp?issn=0378-6323; year=2006; volume=72; issue=4;

spage=315; epage=312; aulast=Bohr.30. Perez-Bernal A, Muñoz-Pérez, Miguel A, Camacho, Francisco. Management of Facial

Hyperpigmentation. Am J ClinDermatol 2000; 1 (5): 26 1-268.31. Phiamphongsant T. Treatment of Melasma: a review with personal experience. Int. JDermatol

1998;37: 897-903.


AUTHORS:1. Vishal Wali2. Suma Patil3. S.K. Patil4. A.S. Hogade5. N.S. Manthale6. P.S. Sagare

PARTICULARS OF CONTRIBUTORS:1. Assistant Professor, Department of DVL, M.R.

Medical College, Gulbarga.2. Senior Resident, Department of DVL, M.R.

Medical College, Gulbarga.3. Professor & Head, Department of DVL, M.R.

Medical College, Gulbarga.4. Professor, Department of DVL, M.R. Medical

College, Gulbarga.

5. Assistant Professor, Department of DVL, M.R. Medical College, Gulbarga.

6. Senior Resident, Department of DVL, M.R. Medical College, Gulbarga.

NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:Dr. Vishal Wali,OPD No. – 6, Department of DVL BTGH,M.R. Medical College, Gulbarga, Karnataka.Email –[email protected]

Date of Submission: 19 /11/2013.Date of Peer Review: 20/11/2013.Date of Acceptance: 28/11/2013.Date of Publishing: 17/12/2013.

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