A Comparative Study on Efficacy of Azithromycin and Doxycycline in the Treatment of Acne Vulgaris at a Tertiary Care Centre

1Pharmacology, Universal College of Medical Sciences, Bhairahawa, Nepal. 2Pharmacology, Universal College of Medical Sciences, Bhairahawa, Nepal. 3Medicine, KS Hegde Medical Academy , Mangalore, India. 4Anesthesia, Kalpana Chawla Medical College, Karnal, Haryana, India. 5Kasturba Medical College, Manipal , MAHE India. 6Pharmacology, Kasturba Medical College, Manipal , MAHE India. *Corresponding author E-mail: navin903@gmail.com

Acne Vulgaris is a chronic inflammatory disorder involving the blockage and/or inflammation of pilosebaceous follicles. It is clinically characterized by comedones, papules, pustules, nodules, cysts and scars. It may have an adverse effect on psychosocial and emotional impact in an individual which may lead to social phobias, withdrawal from society and clinical depression. 1 It characteristically presents as noninflammatory lesions, inflammatory lesions, or a mixture of both affecting mostly the face but sometimes also the back and the chest. A noninflammatory lesion consists of closed comedones and open comedones. Inflammatory lesion present in the form of erythematous macules, papules and pustules in majority of cases. 2 The most common causative organism for acne vulgaris is the anaerobic organism, Propionibacterium acnes (P. acnes). P. acnes is an anaerobic bacteria that can colonize the skin and hair follicles. Several studies have indicated that specific strains of P.acnes are commonly associated with acne vulgaris. P. acnes grows deep inside of the pores, where it feeds on the sebum produced by the sebaceous glands. 1 Acne scar is a common complication to acne. It is of different types and is associated with either loss or increase in collagen. Ice pick scars, which are well defined depressed scars with irregular edges, or atrophic macular scars, which have a superficial shallow depression with wrinkled epidermis is associated with loss of collagen. Increase in collagen occurs in either hypertrophic and/or keloids which can be very disfiguring and causes psychosocial abnormalities in an individual. 2 The main pathophysiology's involved in the development of acne are follicular differentiation, excess sebum production, Propionibacterium acnes and inflammation. 3 The general therapy in the treatment of acne vulgaris includes oral and topical therapy. 4 Topical therapy includes Benzoyl peroxide, Tretinoin, Azelaic acid. Among these benzoyl peroxide is considered a potent antimicrobial agent against bacteria. Benzoyl peroxide is a lipophilic drug which can easily penetrate stratum corneum and enters the pilosebaceous follicles after which it is rapidly broken down to benzoic acid and hydrogen peroxide and generates free radicals that harms the bacterial protein. 5 Oral therapy includes antibiotics such as doxycycline, erythromycin, azithromycin, trimethoprim, etc. Among these, Azithromycin and doxycycline are nowadays used routinely in clinical practice worldwide. 6,7 .

Materials
Type Considering 10% dropouts and subjects that will miss follow up, sample size was 107. To increase the accuracy a sample size of 110 was taken for this study.
Selection criteria: All the patients visiting to the dermatology OPD of Manipal Teaching Hospital with the complaints of acne. Inclusion criteria 1. All patients diagnosed with acne regardless of age and sex. 2. Patient who were willing to participate in the study. Exclusion criteria 1. Pregnant and lactating women with acne. 2. The patients who failed to give consent.
Total cases were divided into 2 groups, each group contained 55 patients. Patients of Group 1 were given Azithromycin 500mg three times a week for one month and the patients of Group 2 were given Doxycycline 100mg once daily for one month. After a period of 4 weeks, each patients were followed up to evaluate number of non-inflammatory lesions, inflammatory lesions and total lesions count as mentioned above. The efficacy of either drugs were also measured with the efficacy parameters stated above.

RESULTS
The mean age of study participants was 21.26 (SD=5.94) years, with the youngest participant being 13 years old and the oldest participant being 56 years old Table 2 shows the age distribution of patients where maximum participants (56) belonged to age group of 20-29 years, followed by < 20 years (47). Only 1 participant was of age above 40 years According to gender, there were more female participants comprising of 73 (66.4% ) than males 37 (33.6%) There was no statistically significant difference (p>0.005) in the lesion characteristics of the two study groups before the commencement of the treatments.
The reduction in the percentage in the number of inflammatory lesions post 1 month was better with azithromycin group as compared There was no statistically significant difference (p>0.005) in the lesion characteristics of the two study groups before the commencement of the treatments.
to Doxycycline, whereas there was improvement with respect to the reduction in number of noninflammatory lesions and total lesions in both groups but was not significant between the groups

DIScUSSIOn
Acne vulgaris is a self-limiting inflammatory disorder of the pilosebaceous unit,which may run a chronic course. It is triggered by Propionibacterium acnes in adolescence and occurs by hypersensitivity of the sebaceous glands to normal circulating dehydroepiandrosterone (DHEA). It is a common skin disorder which can present with inflammatory and non-inflammatory lesions chiefly on the face but can also occur on the upper arms, trunk, and back. Common triggering factors include medications like Lithium, steroids, anticonvulsants; exposure to sunlight;endocrine disorders like PCOD and pregnancy. Heritability estimates range from 50-90% 8 Topical and oral medications can be used for treatment of acne. P. acnes, which is highly sensitive to a number of antimicrobial agents of different classes, including macrolides, tetracyclines, penicillins, clindamycin, aminoglycosides, cephalosporins, trimethoprim, and sulfonamides. 9 Here, we have studied the efficacy of two drugs used routinely in clinical practice worldwide-Azithromycin and Doxycycline.
Azithromycin is a broad-spectrum macrolide antibiotic. It prevents bacteria from growing by interfering with their protein synthesis. It binds reversibly to the 50S subunit of the bacterial ribosome, thus inhibiting translation of mRNA. It is used in the treatment of acne due to its anti-bacterial, immunomodulatory and antiinflammatory properties. Common side effects include diarrhea, nausea and abdominal pain, palpitations, angina, dyspepsia, flatus, vomiting, melena, jaundice, vaginal monilia, vaginitis, nephritis, dizziness, headache, vertigo, somnolence and fatigue 10 Doxycycline is a broad spectrum semisynthetic tetracycline. It inhibits bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit and preventing the association of aminoacyl-tRNA with the bacterial ribosome, thereby giving the immune system time to kill and remove the bacteria. Further inhibition of protein synthesis occurs in mitochondria through binding to the 70S ribosomes. Common side effects include nausea, vomiting, diarrhoea, epigastric burning and oesophagitis. Stevens-Johnson syndrome and toxic epidermal necrolysis may occur with the use of doxycycline. The accumulation of doxycycline in teeth and bones leads to discoloration of teeth. It may also cause enamel dysplasia, bone deformities and impairment in bone growth. It has also been associated with benign intracranial hypertension. 11