INTRODUCTION:

Recurrent tinea infections are a public dermatological disease provoking patients to look for medical advices. Although drug resistance is rare, widespread dermatophytosis cases have been increasing in frequency despite prolonged treatment with oral terbinafine, fluconazole or itraconazole. Many thoughts contributing to relapses have been anticipated but the obvious reasons have not been explained.^1-3 Handling resistant tenia has arisen as health risk in endemic zones like India. Using topical and oral antifungal drugs is commonly used treatment plan by dermatologists for treatment of fungal skin infections.^4-6 algae extracts proved the existence of many antimicrobial action compounds⁷.

Itraconazole is an important antifungal agent which works by inhibiting cytochrome P450-dependent enzyme. The treatment of dermatophytosis at doses 200 mg for 4 weeks daily showed good results.^8-10 Because of frequent relapses at short intervals, some physicians have used it for prolonged periods.^11,12 Sustain release mucoadhesive pill of itraconazole showed ratio of drug release up to 86% for 9 hours¹³. Previously local iodine had been used in treatment of tenia capitis.¹⁴ While tincture of iodine has antiseptic effects and active modes of treatment for molluscum contagiosum skin infection. It was prepared by dissolving the potassium iodide 25gm and the iodine 25gm in the purified water 250ml and adding sufficient alcohol (90%) to produce 1000 ml ¹⁵. There is disturbing increase in cases of dermatophytosis in Iraq. It is difficult to decide whether these recurrences signify resistance to drugs or had other explanations. In this study we add topical 5% tincture of iodine due to its antiseptic properties as an adjuvant to oral itraconazole for recalcitrant dermatophytosis.

MATERIAL AND METHODS:

A comparative study was conducted in the Dermatology and Venereology Department, Ramadi Teaching Hospital, during the period between April 2020 till December 2021. A total number of 130 patients with recurrent tenia were enrolled in this work. Inclusion Criteria: Patient with age above 18 years with chronic recurrent tenia corporis and/ or tenia cruris of more than 2 months duration who have been sufficiently treated and still evolving recurrences within one month of stopping oral antifungal drugs. Individuals without systemic diseases, patients ready for therapy after knowing adverse effects. Exclusion Criteria: Pregnancy and lactation; patients on immunosuppressive drugs; persons who received oral itraconazole drug and/or had contraindications to it including: those with congestive cardiac failure, cardiac arrhythmias, and signs of renal or hepatic disease. A liver function test was carried before and during management for evaluating the side effect of itraconazole. Patients were asked regarding: age, gender, duration, job, residence, type of tenia, associated symptoms as itching and pain, family history of recurrent attacks of tenia. Physical examination was carried out regarding site, size of lesions. The study was fully described to the participants and the need for pre-and post-treatment photographs explained for them and a formal agreement was obtained after full explanation to each individual about the disease, course, prognosis and treatment. All patients were diagnosed on clinical basis and direct microscopic examination using potassium hydroxide mount (KOH) of scales obtained by scraping the skin lesion. Those with positive superficial dermatophytosis were randomly divided into two groups depending on the mode of therapy, which were compared and evaluated as follows:

Group A: patients treated by oral itraconazole 100mg/ Twice/ day. (FuSpore, batch No: XC1E002, Canada).

Group B: cases treated by oral itraconazole 100mg/ Twice/ day, in combination with 5% topical tincture of iodine used three times weekly overnight.

Evaluation is done by clinical assessment in terms of clinical score and rate. The response to treatment was defined as the following:

1. Complete healing= no erythema, no scale, no hyperpigmentation, negative direct microscopic examination.

2. Marked improvement= hyperpigmentation, no scale, negative direct microscopic examination (stop treatment)

3. Incomplete healing= hyperpigmentation, no scale, positive direct microscopic examination.

4. No changes= erythema, scale, positive direct microscopic examination.

5. Worse.

Ethical considerations:

This research was permitted by the Ethical Committee at “the College of Medicine, University of Anbar (Ref. No 84/23-6-2021),” and written consent was obtained from each patient before enrollment in the study.

Statistical Analysis:

The data were investigated using “Microsoft Excel 2010 and SPSS version 22. The hypothesis was tested using Chi-square tests and t-test.” A p-value <0.05 was considered to represent a significant difference.

RESULTS:

A total of 130 patients were enrolled in this study. Ten cases were defaulted after the first visit for unknown reason, while the remaining 120 cases completed the study, 82(68.3%) were males, and 38(31.7%) were female. The age ranged (18-60 years) with mean (± SD) 33.3+12.7. There were significant differences in their residency, and 98(81.7%) lived in urban areas, while 22 (18.3%) lived in rural areas. Disease duration ranged between (8-46 weeks) with mean (±SD) 16.7+10.8, while 92(76.7%) had positive family history.The surface area involved by using palm method (ranged 1-12) with mean (±SD) 4.8+2.9. Clinical types were tenia corporis, tenia cruris, and both (tenia corporis and cruris). Marked improvement and clinical cure within 2 weeks were highly significant level in 44(75.9%) patients of group B, VS 14(24.1%) of cases of group A. At 4 weeks, mycological cure and complete healing were reported in 21(95.4%), 1(4.6%) cases of group B and A respectively. Six weeks later, the clinical cures were not significant different between both groups. Next visit at 8 weeks, complete healing accounted in 88 participants, 60(68%) patients in group B and it was statistically more significant level than 28(32%) individuals of group A, p value 0.001(Table 1). There was no significant difference in disease curing at 12 weeks follow up. Complete healing reported in 107 patients, where 60 (57%) cases in group B and 47(43%) individuals of group A. p value 0.209. Tolerated side effects to itraconazole appeared during initial 2 weeks of therapy and resolved during study, which including: headache that reported in 8(6.6%) patients, nausea in 6(5%) cases. There was no significant change in the levels of “Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT)” before initiation of itraconazole therapy, and at 2 or 6 weeks. No major side effects were recorded apart from transient slight irritation mild burning sensation that was noticed following 5% iodine tincture application in 20(80%) patients.

Table -1: The clinical responses of both groups

Clinical response	Total	Group A	Group B	Chi- Square	p value
(2 weeks)
Marked improvement	58	14(24.1%)	44 (75.9%)	15.517	0.000
Incomplete healing	37	21 (56.8%)	16 (43.2%)	0.676	0.411
No changes	25	25 (100%)	0	-	-
(4 weeks)
Complete healing	22	1(4.6%)	21 (95.4%)	-18.182	0.0001
Marked improvement	62	23 (37%)	39 (63%)	4.129	0.042
Incomplete healing	36	36 (100%)	0	-	-
(6 weeks)
Complete healing	51	15 (29.4%)	36 (70.6%)	8.647	0.003
Marked improvement	56	32 (57%)	24 (43%)	1.143	0.285
Incomplete healing	13	13 (100%)	0	-	-
(8 weeks)
Complete healing	88	28 (32%)	60 (68%)	11.636	0.001
Marked improvement	27	27(100%)	0	-	-
Incomplete healing	5	5 (100%)	0	-	-
(12 weeks follow up)
Complete healing	107	47(43%)	60(57%)	1.579	0.209
Marked improvement	13	13(100%)	0	-	-

DISCUSSION:

Recurrent dermatophytosis are increasing in humid and hot climate like in Iraq, and running major outbreak and become a big challenge to dermatologists and community.¹⁶ Many topical and systemic antifungal drugs failed to get rid of this problem. Gender of the patients in the present study had a statistically significant effect on fungal skin infection; it was higher in males with 68.3% cases, in comparison to females with 31.7% cases. This may be related to their outdoor working, life activities and job. The incidence of dermatophytosis in men was more than women in many earlier studies, a result similar to the current work^16-18. The observation of recurrent cases is on line with new appeared terbinatine resistant Trichophyton mentagrophytes type VIII from India and Iraq.^19,20In daily practice, the first choice is itraconazole but still there are relapses. Therefore, author need to add effective antiseptic adjuvant. The cheaper and available one is tincture of iodine were evaluated. Tenia corporis and tenia cruris are generally cutaneous and limited to the cornified layers because of the incapability of fungi to penetrate the deeper tissues or organs of immune-competent hosts.^{2, 21} The purpose of the present work is to re-evaluate oral itraconazol action in recurrent dermatophytosis alone and to assess 5% tincture of iodine as an add on treatment. The effect was interesting at 2 weeks of combination of both agents were 75.9% of cases showed clinical cure and synergistic activity. While oral itraconazol alone was effective with marked response in 24.1% of patients. The difference between them reaches statistically very significant level. At 4 weeks, complete cure rate of 95.4% of patients with combination therapy. As compared to monotherapy with itraconazole in 4.6% of individuals. So the topical 5% tincture iodine and oral itraconazol was better than oral itraconazol alone. A similar study using combination of topical amorolfine with oral itraconazol was more effective than oral itraconazol only. ²² Others used Keratinolytic enzymes along with other topical antifungal drugs and successfully potentiate the antifungal therapy²³. There was no significant difference between both groups in clinical cure regarding the erythema, scale, hyperpigmentation, and negative direct microscopic examination after 3 months follow up, p value 0.209. Previous report shows that only 50% healing rate with 3 weeks 200mg/day itraconazole treatment. Hence combination treatment seems more useful,^25-28 and the double drugs therapy will get synergistic or additive action and found it decreases the accident of resistance. The drugs draw backs were of mild severity and no one of the participants required cessation of therapy. This study did not report any abnormality of liver function and the adherence to treatment was excellent. Previous reports found that oral itraconazole is safe formulation. ^{29, 30} The long intake duration of oral itraconzol and there is no group trail for topical 5% tincture of iodine alone, are the limitations of this work.

CONCLUSION:

To our knowledge, this is the main Iraqi repots providing the evidence that the frequently used management policy of combination of topical and oral antifungal drugs is successful and harmless in treatment of recurrent tinea infections. Also shows that topical 5% iodine tincture plus oral itraconazole is associated with enhanced antifungal action.

CONFLICT OF INTEREST:

The authors have no conflicts

ACKNOWLEDGMENTS:

The authors would like to thank all who support us.

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Received on 30.04.2022 Modified on 28.06.2022

Research J. Pharm. and Tech 2022; 15(12):5825-5828.

DOI: 10.52711/0974-360X.2022.00983