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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 4  |  Page : 263-267

Therapy: Resistant dermatophyte infection in India-clinico mycological study


1 Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
2 Department of Dermatology Yenepoya Medical College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
3 Scientist, Center for Research in Medical Devices, Galway, Ireland
4 Department of Microbiology, Yenepoya Medical College, (Deemed to be University), Mangalore, Karnataka, India
5 Department of Dermatology, District Wenlock Hospital, Mangalore, Karnataka, India
6 Kanavu Skin Clinic, Puttur, Karnataka, India
7 Skincare and Laser Center, Udupi, Karnataka, India
8 School of Chemistry, National University of Ireland, Galway, Ireland

Date of Submission31-Dec-2021
Date of Decision07-Jan-2022
Date of Acceptance10-Jan-2022
Date of Web Publication25-Jun-2022

Correspondence Address:
Dr. Manjunath Mala Shenoy
Department of Dermatology, Yenepoya Medical College, Deralakatte, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_135_21

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  Abstract 


Background: There is a high frequency of recurrent, chronic, and therapy-resistant dermatophyte infections reported from India. Objectives: The study was carried out to identify the epidemiologic factors, clinical features, and causative agents associated with therapy-resistant tinea corporis. Subjects and Methods: Patients above 18 years of age, diagnosed by dermatologists, and received systemic therapy for at least 3 weeks with inadequate response or relapsed within 4 weeks of cessation of therapy were taken for the study. Demography, clinical features, and results of mycological examination were retrieved. Results: A total of 64 (33.7%) patients were included after screening 190 patients. There were 33 (51.6%) males and 31 (48.4%) females, and most patients (51, 79.7%) were young adults (18–45 years). Family history was obtained in 50 (78.1%) patients. Tinea cruris was associated in 50 (78. 1%) and tinea faciei in 15 (23.4%) of cases. Topical corticosteroids were used by 46 (71.87%) patients in the past. The past therapy with oral itraconazole (46 cases, 56.25%) was the most common to be used. Comorbidities were found in 7 (10.9%) patients. Trichophyton mentagrophytes in 55 cases (85. 9%) was the most common isolate followed by Trichophyton rubrum (7, 10.9%) cases associated with therapy-resistant tinea corporis. Conclusion: Therapeutic failure is alarmingly common in the current scenario of dermatophytosis in India. Failure is probably seen with all common isolates but the most common among T. mentagrophytes. Younger patients, high contagious nature, and concomitant tinea faciei may be associated with a higher risk of therapy resistance.

Keywords: Epidemiology, therapy-resistant tinea, tinea corporis, Trichophyton mentagrophytes


How to cite this article:
Amin N, Shenoy MM, Keekan KK, Pai V, Halady DK, Kanavu NS, Killur LR, Ganesha KK. Therapy: Resistant dermatophyte infection in India-clinico mycological study. APIK J Int Med 2022;10:263-7

How to cite this URL:
Amin N, Shenoy MM, Keekan KK, Pai V, Halady DK, Kanavu NS, Killur LR, Ganesha KK. Therapy: Resistant dermatophyte infection in India-clinico mycological study. APIK J Int Med [serial online] 2022 [cited 2022 Dec 4];10:263-7. Available from: https://www.ajim.in/text.asp?2022/10/4/263/348292




  Introduction Top


Cutaneous mycoses are commonly caused by keratinophilic filamentous fungi called dermatophytes. These infections are encountered worldwide but found prominently in tropical countries like India due to favorable climate. Dermatophyte infections were curable previously with antifungals for a short duration. There is an increasing trend of dermatophyte infection over the past few years in India, along with a high frequency of recurrent, chronic, and therapy-resistant infections.[1],[2],[3] With this changing trend, there is a need for relook at the epidemiology and the causative fungal agents. There is a dearth of knowledge on therapy-resistant dermatophytosis in India although few studies have highlighted the epidemiology.[4],[5],[6],[7],[8] This study was aimed at identifying clinical features, epidemiological factors, and causative agents associated with therapy-resistant tinea corporis.


  Subjects and Methods Top


A retrospective descriptive study was undertaken in the department of dermatology of a tertiary care medical college hospital from July 2019 to December 2019. The study received approval from the institutional ethical committee with the reference number YEC-1/2020/079. Data of patients with a clinical diagnosis of tinea corporis from different taluks of Dakshina Kannada district of Karnataka state, India, were evaluated. The hospital information system and the referral letters were used to collect the requisite data. Patients aged 18 years or above, diagnosed as therapy-resistant tinea corporis and positive for direct microscopic examination and fungal culture for dermatophytes were included. Therapy-resistant tinea was defined as those cases that were treated by a dermatologist by systemic antifungal for at least 3 weeks but exhibited inadequate response or relapsed within 4 weeks of cessation of therapy. Direct microscopy was performed by examining the skin scrapings under microscope after digestion by 10% potassium hydroxide mount; the presence of smooth branching hyphae was considered positive. Mycological culture was performed incubating the skin scrapings in Sabouraud Dextrose Agar with and without antibiotics at 28°C, up to 4 weeks. Isolates were identified by the colony characteristics and microscopy under tease mount/slide [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f. Data pertaining to the demography, past therapy details, clinical findings, direct microscopic examinations, and culture isolates of dermatophytes were tabulated. Clinical images, which had been obtained after taking the consent, were also retrieved [Figure 2]a, [Figure 2]b, [Figure 2]c.
Figure 1: (a) Trichophyton mentagrophytes colonies on Sabouraud's Dextrose Agar; flat, creamy, and granular surface with reverse yellow-brown pigmentation. (b) Trichophyton rubrum colonies on Sabouraud's Dextrose Agar; flat, creamy, and downy with reverse red pigmentation. (c) Nannizzia gypsea colonies on Sabouraud's Dextrose Agar; flat, creamy, and granular with reverse yellow-brown pigmentation. (d) Microscopy of Trichophyton rubrum showing microconidia in “bird on fence” appearance. (e) Microscopy of Trichophyton mentagrophytes showing spiral hyphae. (f) Microscopy of Nannizzia gypsea showing spindle-shaped macroconidia

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Figure 2: Clinical presentation of tinea faciei (a), tinea cruris (b), and tinea corporis (c)

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  Results Top


A total of 190 patients were screened, and 64 (33.7%) were analyzed after satisfying inclusion and exclusion criteria. Fungal isolation details are given in [Table 1]. Trichophyton mentagrophytes in 55 (85.9%) cases was the most common isolate followed by Trichophyton rubrum 7 (10.9%); Nannizzia gypsea in 2 (3.1%) cases.
Table 1: Fungal species isolated (n=64)

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Demographic and clinical details of the total 64 cases are given in [Table 2] and [Table 3]. There were 33 (51.6%) males and 31 (48.4%) females, with 51 (79.7%) being young adults. Fifty (78.1%) patients gave history suggestive of tinea in the family members. Duration of disease ranged from <3 months up to 2 years. Tinea cruris was associated in 50 (78.1%) and tinea faciei in 15 (23.4%) of cases. Among 64 patients, 54 (84.4%) gave history of reoccurrence within 1 month of treatment, and the rest 10 (15.6%) did not show adequate response in 3 weeks. Topical corticosteroids (TCS) misuse was recorded in 46 (71.9%); however, there was no TCS usage in the past 4 weeks. Taluk-wise distributions of the cases and isolated fungal agents have been summarized in [Table 4].
Table 2: Demographic data of patients in the study (n=64)

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Table 3: Clinical details of the treatment-resistant dermatophytosis

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Table 4: Clinical details of the treatment-resistant dermatophytosis

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  Discussion Top


This study was conducted in a tertiary care center located in a coastal district of Karnataka state of India. Tropical monsoon weather is favorable to fungal infections. According to the 2011 census, there were five taluks (subdivision of districts), namely Mangalore, Bantwal, Belthangady, Puttur, and Sullia, with a total population of about 2,900,000. Dermatologist's services are available in all these taluks. The study center is a tertiary care hospital in the Mangalore Taluk, and cases are referred by the dermatologists from the other taluks for advanced care to the patients.

Recalcitrant and resistant dermatophytosis is common in the current scenario of dermatophytosis in India. In vitro resistance has not been clearly defined since minimum inhibitory concentration cutoff values for the dermatophytes have not been determined. Concordance between the in-vitro resistance and clinical response has also been debated.[9] The term “recalcitrant” has often been used to encompass all the persistent infections after standard treatment in the settings of chronic, recurrent, corticosteroid-modified, and resistant cases.[10] No specific duration was mentioned to define the recalcitrant in the definition, and it is difficult to interpret the effect of prior usage of TCS on the therapeutic outcome. Textbook treatment regimens for tinea corporis vary between 2 and 4 weeks with systemic antifungals such as itraconazole and terbinafine.[11],[12],[13] Hence, we defined therapy resistance as a relapse or inadequate response despite a case being treated by a dermatologist with topical and/or systemic antifungal for a duration of at least 3 weeks.

Our objective was to determine the most common causative agent associated with therapy-resistant tinea and to determine the clinico-epidemiological factors associated with it. Dermatophytosis is caused by many species of filamentous fungi belonged to 3 genera Trichophyton, Microsporum, and Epidermophyton, based primarily on morphology of colony and macroconidia. More genera have been described, and a molecular classification has identified with the addition of subspecies.[14] Our isolation rate was lower (42.67%), which is due to the inclusion of patients who received oral antifungal therapy who are often negative for culture. We identified T. mentagrophytes as the most common isolate accounting for almost 86% of cases. In majority of the studies conducted after 2010, T. mentagrophytes has been isolated as the dominant pathogen of glabrous tinea.[1],[15],[16],[17] This study results indicate that T. mentagrophytes is the leading cause of therapy-resistant tinea. We isolated T. rubrum and N. gypsea in small proportions of cases. T. rubrum was the most common species of dermatophytosis for many decades.[18],[19] N. gypsea, geophilic dermatophytes, is not a common isolate. It may mimic other inflammatory dermatosis leading to misdiagnosis.[20] This can be a reason for the delay and failure of standard therapy.

There are two major transformations in the epidemiology of the current scenario dermatophytosis in India. First is the isolation of T. mentagrophytes as the most common isolate. Second is the large-scale mistreatment of the dermatophyte infections by the potent TCS-containing creams due to their over-the-counter (OTC) availability and advice by unqualified practitioners.[2],[4],[6] Majority of these creams are a combination of antifungal-antibacterial and potent TCS, which are primarily marketed to obtain quick relief of symptoms. Patients often use them for months with undesirable consequences. TCS abuse in our patients was a high magnitude of about 72%. TCS hence appears to be an important confounder; however, it may not be the only cause of treatment failure. Agent and environment-related factors do contribute to the development of therapy resistance. T. mentagrophytes seems to possess several virulence factors which lead to frequent treatment failure. It is currently proven that the prevailing subspecies in India have shown a high tendency for terbinafine resistance.[7],[21],[22] It may be highly contagious leading to high chance of occurrence among close contacts like family members.[2],[4],[5],[6],[23] In our study, family history was as high as 78% indicating a highly contagious nature of infection. Persistence of infection in family may also indicate certain genetic predispositions. Such occurrence may be seen with other species of dermatophytes too.[23]

Our patients were distributed among various occupational groups, both indoor and outdoor. Occupation may have a minor impact on therapy resistance. Majority of our patients were young adults, and therapy resistance appears to be more common in this age group. This may be related to lifestyle habits and poor treatment compliance. Increased use of tight and synthetic garments may be an important factor for recurrence.

About 30% of the cases qualified as chronic dermatophytosis.[9] Tinea faciei was noticed in almost one-fourth of the cases. It is a rarer form and may be relatively more common in children.[5],[24] It may contribute to the recurrence and therapy resistance due to the vellus hair involvement, especially in a background of TCS misuse.[25] Failure to terbinafine is common in the current scenario.[26],[27] Majority of our patients were healthy, and comorbidities were present in only seven with diabetes as the leading cause. The presence of comorbidities may not contribute to the resistance to treatment. We compared the occurrence of dermatophytes within Dakshina Kannada District, and we found that both T. mentagrophytes and T. rubrum were isolated from all five taluks. N. gypsea was isolated in one case from Mangalore and Bantwal Taluk.

This study on clinical and epidemiological aspects of therapy-resistance tinea highlights several aspects such as involvement of younger patients, high contagious nature, high frequency of co-occurrence of tinea faciei, TCS misuse in a large scale and dominance of T. mentagrophytes as the isolated agent. There are few limitations like relatively smaller sample size and identification of the causative agent by conventional method only and not by molecular methods. Many findings in the study need to be reconfirmed by larger and multicenter studies. Tropical countries are often burdened with several neglected dermatological diseases such as leprosy, leishmaniasis, and cutaneous tuberculosis.[28],[29],[30] Therapy-resistant and recalcitrant tinea appear to be an addition to the expanding list. Generating no intuitive information about the prevalence, morbidity, specific clinical factors, and associated fungal isolate in a larger cohort of studies can serve to develop a comprehensive therapeutic strategy. The current study highlights the need for counseling the patients with specific measures to prevent spread among family members. Lifestyle-related factors, especially among young adult patients have to be discussed in detail.[9] Through counseling to avoid OTC purchase of TC-containing creams as an easy remedy is needed. Therapy of dermatophytosis shall be comprehensive that includes adequate duration of therapy as well as advice on measure to prevent recurrences.

Acknowledgments

Mrs. Nikhitha Amin is a recipient of the Indian Council of Medical Research (ICMR) - Senior Research Fellowship (AMR/Fellowship/9/2020 - ECD- II).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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