INTRODUCTION:

Topical corticosteroids (TCS) are perhaps the most commonly prescribed medications in dermatological practice and since its introduction in 1951, they are increasingly used for a wide range of skin diseases⁽¹⁾. Further development of the fluorinated TCS made a variety of options for steroid potency for the dermatologists to be used. Meanwhile, an increased incidence of TCS adverse effects were reported including striae distance, cutaneous atrophy, hypertrichosis and telangiectasia.⁽²⁾Chronic misuse of TCS on the face produced a clinical condition which was described by various names one of these is Steroid Rosacea⁽³⁾.

The main clinical features of SIR are diffuse facial redness, flushing, telangiectasia, papulopustular eruption and the development of the rebound phenomenon after steroid withdrawal⁽⁴⁽.

Specific treatments for Erythematotelangiectatic rosacea

· Topical treatments: Metronidazole gel, Azelaic acid, Brimonidine and Oxymetazoline.⁽⁵⁾

· Oral drugs which have vasoconstriction properties: as adrenergic antagonists, Mirtazapine (alpha-blocker), propranolol (beta-blocker) or carvedilol (both alpha and beta blocker).⁽⁶⁾

· Laser therapies: that target vessels have been used as Pulsed dye laser (595) nm, Nd: YAG (1064) nm or IPL (515-1200)nm.^(7,8)

Topical Vitamin K Cream:

Topical vitamin K application can be used for several medical purposes like the prevention of aging vascular manifestations, decreases skin pigmentation as in periorbital hyperpigmentation which combined with other topical vitamins, for bruising resolution and the therapy of many superficial dilated blood vessels disease like facial telangiectasia^(9,10⁾.

Vitamin K may facilitate the removal of extravascular blood from the skin, which accounts for its effectiveness in hastening the clearing of bruising and reducing its severity after laser treatment.⁽¹¹⁾

A preliminary study appears to suggest that cosmetic creams with vitamin K oxide are more active for post-laser purpura than non-oxide vitamin K creams.^(12,13)

PATIENTS AND METHODS:

This was a randomized, single-blind, placebo-controlled clinical trial, conducted in the Department of Dermatology and Venereology in Al-Kindy Teaching Hospital, Baghdad-Iraq during a period of 19 months from (April 2017 to Nov. 2018) for assessing the effectiveness of topical vitamin K cream 1% in treatment of SIR. This study involved 75 patients who diagnosed with SIR and divided randomly into two groups: Group A: Patients who treated with topical emollient (Aquasoft cream) and their number was 25 patients. Group B: Patients who treated with the topical vitamin K cream 1% (pharmaceris) and their number was 50 patients. All patients instructed to apply treatment in a thin layer to all affected areas twice daily for a period of two months.

All females diagnosed with erythematotelangiectatic subtype of SIR for both systemic steroid or facial TCS misuse (either continuous for a period of more than one month or intermittent for more than six months). The exclusion criteria included: Idiopathic rosacea, Papulopustular stage of SIR, Pregnant and lactating women, Patients who deny any history of TCS misuse on face, and Patients with rosacea-like lesion due to other cause such as high dose of vitamin B6 and B12, amiodarone, oral acetazolamide, pimecrolimus cream 1% , progesterone -releasing IUCD.A proper history was taken from patients regarding the demographic data. Patients were thoroughly examined, assessment of flushing, non-transient erythema, telangiectasia, burning, dryness. Patients being treated were instructed to discontinue all TCS preparations at least one week before entering the study, avoid factors which exacerbate the condition (sun, spicy foods, hot drinks, heat exposure, alcohol and Fluorinated toothpastes) and to apply the cream in a thin layer covering the entire affected sites twice daily. Medical photographic documentation of the patients were done using digital camera of Samsung galaxy S7 before study, after 4 weeks and 8 weeks of the study.

Erythematotelangiectatic severity scoring system: was modified from Standard grading system for rosacea: Report of the National Rosacea Society Expert Committee of JAAD⁽¹⁴⁾ into five parameters each one was graded according to the severity into four grades as Absent, Mild, Moderate and Severe and these grades were scored as 0,1,2 and 3 respectively. The assessment of the patients was done at every visit by the sum of these scores for all parameters.

*Mild SIR score range (1-5) as example shown in Figure (1), Moderate SIR score range: (6-10) as example shown in Figure (2) and sever SIR score range: (11-15) as example shown in Figure (3).

Figure (1) Mild SIR Figure (2) Moderate SIR Figure (3): Sever SIR

Ethical consideration:

· Informed verbal consent was taken from the patients who were free to reject or withdrawal the consent at any time of the study period.

· All information was kept anonymous and confidentiality was insured to the patients and the collected data were used for scientific purpose only.

Statistical analysis:

The data analyzed using Statistical Package for Social Sciences (SPSS) version 25 presenting as mean, standard deviation. Categorical data presented by frequencies and bar chart. Analytic statistics were displayed using Chi-square-test and t test. P-value less than 0.05 was considered significant as a point for discrimination.

RESULTS:

Topical vitamin K cream 1% was assessed in the study of 75 patients diagnosed with SIR-erythematotelangiectatic subtype, divided into two groups: 25 patients were treated by topical emollient Aquasoft cream (Group A) as a control group and 50 patients were treated by topical vitamin K cream 1% (Group B) as a study group.

The females represented the studied gender and their age was ranging from 8 to 50 years with a total mean of 37.1 years and standard deviation (SD) ± 3.022 years.

The distribution of women regarding their ages revealed that the differences between the two groups were not significant (Table 1).

Table (1): The mean age and standard deviation for both groups.

0.247

4.232

38.2

Group A

3.251

35.7

Group B

3.022

37.1

Total

The study assessment:

The mean score for SIR in the first visit was 7.76±2.947 and 7.58±3.89 for group A and B respectively and it was decreased in both groups but it was significant in treated group compared to control group. As shown in Table (2). P-value between the two groups at 4 weeks was significant and it was highly significant at 8 weeks. As shown in Table (3).

Table (2): Descriptive of both groups by T-test at each visit.

	Baseline		4wk		8wk
	Mean	SD	Mean	SD	Mean	SD
Control N=25	7.76	2.947	6.64	2.899	6.4	2.828
Study N=50	7.58	3.89	4.24	3.402	2.6	2.92
T-test	0.128		2.669		4.349
P-value	0.899		0.013		0.000

Table (3): ANOVA test between the three visits for both groups

	Baseline and 4w		Baseline and 8w		4wk and 8wk
	P-value		P-value		P-value
Control N=25	0.247	NS	0.209	NS	0.185	NS
Study N=50	0.007	S	P <0.001	HS	0.013	S

*NS: Non-significant. S: Significant. HS: Highly Significant.

Figure 4 show the sever SIR form before and after 8 weeks of therapy with vit. k twice daily to become mild form.

Figure (4.A and B): The left side of SIR before and after 8 weeks of treatment with vit. k.

The side effects:

The females requested anun scheduled visit on account of flaring of erythema, burning and dryness in the first two weeks of vitamin K therapy but gradually declined and improved on the 4 week visit then the response rates increased throughout the study without discontinuation of the therapy as shown in Table (4).

Table (4): The side effect of the study group

6 (12%)	21 (42%)	30 (60%)	Erythema flaring
10 (20%)	12 (24%)	20 (40%)	Burning
2 (4%)	11(22%)	26 (52%)	Dryness

DISCUSSION:

Steroid-induced rosacea (SIR) is a condition resulting from prolonged steroids misuse and the rebound phenomenon which appears after its discontinuation particularly fluorinated steroids and often associated with eruption resembling rosacea called as iatrosacea.⁽¹⁵⁾

TCS are among the most commonly prescribed medication in dermatology mediated by its anti-inflammatory, vasoconstrictive, anti-proliferative, and immunosuppressive effects⁽¹⁶⁾.

The reasons for this increase in the incidence of SIR include non-standard clinical management, regulatory loopholes that enable beauty salons to use corticosteroids inappropriately with different potency, widespread availability of TCS and poor understanding of the appropriate use of corticosteroids among patients.⁽¹⁷⁾

During the 8-weeks treatment period of our study regarding the Aquasoft treated group, there were 24% of patients presented with mild severity, 60% moderate and 16% severe, at the end of the study there were 40%, 52% and 8% of them became mild , moderate and severe respectively and showed decrease in P-value, but not statistically significant.

While in vitamin K group at the onset of current study, there were 42% mild, 32% moderate and 20% severe and after finishing the study, 42% of them had complete improvement and without any features, 48% and 10% became mild and moderate respectively and no one was severe.

The mean of Erythematotelangiectatic severity score reduced in both groups (the control group and the treated group), but it was statistically significant in treated group.

In vitamin K treated group the p-value was statistically significant in the first 4 weeks and it was highly significant at the end of 8 weeks of therapy.

This study was stimulated by the encouraging the results of Dr. Irena Eris who conducted a study to evaluate the safety and the efficacy of cosmetic product for skin with dilated capillaries containing 1% of vitamin K epoxide (vitamin K oxide) which done in Dermatological Centre of Miedzyleski Hospital, Warsaw, Poland of 26 women in age from 28-68 years with complain of facial redness, erythema and telangiectasia for a duration of 56 days with twice daily use and revealed a reduction in the facial redness and the visibility of telangiectasia which more effectively than placebo group and the topical vitamin K was non-photo toxic to UVA and UVB.⁽¹⁸⁾

The study of Elson et al⁽⁹⁾ showed the effects of topical application of topical vitamin K 1% mixed with retinol, topical vitamins C and E on infra orbital dark circles and wrinkles of the lower eyelids in Japan of 57 patients which showed that topical vitamin K was useful in dark eye circles and had significant effect in removing hemostasis and clearing the purpura particularly early on and decrease periorbital wrinkles.

The study of Karavani⁽¹⁹⁾demonstrated that topical vitamin K was safe and also it was nonirritant even after applying it since the second day post-blepharoplasty.

Several studies support the efficacy and the role of topical vitamin K to reduce purpura post-procedural of pulse dye laser^(12,20,21)which reported that topical vitamin K act to hasten resolution of laser-induced purpura and it is useful in accelerating the resolution of facial bruising from cosmetic procedures while another study in 2016 done to evaluate the efficacy of topical vitamin K versus urea cream 5% in Thailand of 20 patients on purpura post Q-switched Nd: YAG (1064) nm which showed that topical vitamin K was faster onset of action and started on its effect on the second day to lighten the purpura and it was completely cleared at the sixth day which seemed to be superior to urea cream but the lightening effects was not significantly noticeable to others.⁽²²⁾

CONCLUSION:

The use of topical vitamin K was effective therapeutics option in treatment of SIR with rapid improvement in the flushing, non-transient erythema, telangiectasia, burning and dryness with mild and tolerable side effects.

ACKNOWLEDGMENT:

I would like to express my great thanks to my colleagues in AL-KINDY Teaching Hospital. Special thanks to Dr. Maoal Sabah resident in Department of Dermatology in Al-Kindy Teaching Hospital.

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Received on 16.09.2019 Modified on 18.11.2019

Research J. Pharm. and Tech. 2020; 13(8):3883-3886.

DOI: 10.5958/0974-360X.2020.00687.3