Epidemiological Trends and Clinicomycological Profile of Chronic Dermatophytosis: A Descriptive Study From South India.

BACKGROUND: Chronic dermatophytosis refers to persistent or recurrent episodes of dermatophytosis lasting for more than 1 year despite adequate treatment with topical and systemic antifungal agents. The rise in the number of these cases is alarming over the past 5 to 6 years, and a thorough knowledge about the reasons for chronicity of dermatophytosis may go a long way in the treatment and prevention of this infection. AIMS AND
OBJECTIVES: The aim of this study was to investigate the epidemiology, various clinical types, and factors associated with chronicity in patients with chronic dermatophytosis, and to isolate the etiological agents and study the clinicomycological correlation.
MATERIALS AND METHODS: Detailed history and clinical details of all patients with chronic dermatophytosis who presented to our tertiary care center over a span of 1 year were recorded. Skin scrapings from these patients were subjected to potassium hydroxide mount and culture in modified Sabouraud's dextrose agar medium.
RESULTS: Sixty-four patients were enrolled in this study with a mean age of 44.5 years. The mean duration of infection was 3.14 years. Tinea corporis was the most common clinical type seen in 46 (71.9%) patients, affecting commonly the waist area in females and the back in males. Bronchial asthma was the most frequent systemic association affecting 20 (31.3%) patients followed by diabetes mellitus, which was present in 13 (20.3%) patients. About 34% patients had a history of long-term steroid use. Among the 28 isolates, Trichophyton mentagrophytes was the most frequent species isolated (46.4%), followed by Trichophyton rubrum (39.3%). Trichophyton tonsurans and Trichophyton verrucosum were isolated from two patients each.
CONCLUSION: Extensive area of involvement, atopy, diabetes, and long-term use of systemic corticosteroids were associated with chronicity. Unlike in the yesteryears, T. mentagrophytes has emerged as the most common etiological agent of chronic dermatophytosis. Copyright:

Introduction

Dermatophytosis is a superficial fungal infection of keratinized tissue caused by dermatophytes that utilize keratin as the source of nutrients and colonize keratinized tissues, namely, stratum corneum of epidermis, nail, and hair. Chronic dermatophytosis was defined by Kamaan in 1978 as a refractory infection that persists for more than 1 year with or without recurrence or a total duration of more than 1 year.[1] Hay in 1982 considered it as a persistent infection for 3 years in spite of treatment with griseofulvin for 3 months.[2] The prevalence of chronic dermatophytosis, which is on an alarming rise in the past few years, especially in the tropics, poses a management challenge to dermatologists. In spite of this, adequate research in this field and modified treatment guidelines are conspicuously lacking.

This rising trend and inadequate clinical response to conventional treatment regimens could be due to various host, environmental, and etiological agents or pharmacological factors. High temperature and relative humidity along with tight clothes and occlusive footwear have been linked to the high prevalence of this infection.[3] Patients with immunocompromised status, diabetes mellitus, atopy, and intake of systemic corticosteroids are predisposed to chronic dermatophytosis.[4] Another predisposing factor particularly relevant for a developing country like India in the past few years is the rampant abuse of topical steroid and antifungal combination creams either by the patients themselves fuelled by the widespread over-the-counter availability or as prescribed by the general practitioners.[5] While Trichophyton rubrum is the most common causative organism associated with chronic dermatophytosis, there have been reports of Trichophyton mentagrophytes, Trichophyton tonsurans, Trichophyton verrucosum, Trichophyton violaceum, Trichophyton simii, Microsporum gypseum, and Epidermophyton floccosum being isolated from chronic cases of dermatophytosis from various parts of India.[4678] Owing to the piling reports of nonresponsive dermatophytosis with a prolonged course, it is highly imperative to look into the various factors associated with chronicity including the causative organisms. This study was done to bring out the trend in age, sex, distribution, causative species and factors associated with chronicity in dermatophytosis.

Materials and Methods

This descriptive study was conducted in the Mycology section of the Department of Dermatology in a tertiary center in Chennai after obtaining Institutional Ethical Committee approval. Patients having dermatophytosis for a duration of 1 year and above despite adequate treatment were selected for the study. Those patients who had dermatophytosis for more than 1 year but reported a history of using topical or systemic antifungal drugs in the prior 3 weeks were excluded from the study.

Detailed case history and clinical features of each patient were recorded. Complete hemogram, absolute eosinophil count, IgE levels, blood sugar, and liver and renal function tests were done to detect associated disorders. Blood Venereal Disease Research Laboratory test for syphilis and enzyme-linked immunosorbent assay for human immunodeficiency virus (HIV) infection were done in high-risk patients. Skin scrapings were collected from all the patients and examined in 10% potassium hydroxide (KOH) for the presence of fungal elements. The active border of the lesion was cleaned with 70% alcohol, and the scales were scraped. Subungual debris was collected from those with nail involvement and examined in 40% KOH. All the specimens were subjected to culture by inoculating on modified Sabouraud's dextrose agar medium with chloramphenicol and cycloheximide and incubated at 28° Celsius. The macroscopic appearance of the isolate was observed weekly for 4 weeks, and microscopic features in lactophenol cotton blue mount were examined for identification of the isolates.

Results

Age and sex distribution

Sixty-four patients with chronic dermatophytosis satisfying all the inclusion and exclusion criteria were enrolled in this study. Of them, 27 were males and 37 were females. The age of the patients ranged from 13 to 86 years with a mean age of 44.5 years [Table 1].

Table 1

Age and sex distribution of patients with chronic dermatophytosis

Age-group (years)	Male	Female	Total (n=64)
11-20	2	-	2
21-30	1	5	6
31-40	6	13	19
41-50	7	7	14
51-60	10	10	20
61-70	-	1	1
71-80	-	1	1
81-90	1	-	1

Out of the 64 patients, two each reported a history of contact with pet animals and cattle. Eight (12.5%) patients gave a history of other family members being affected by dermatophytosis. There was a history of sharing of towels and bath soaps among seven of these patients (odds ratio >1).

Clinical features

The body surface area (BSA) affected by dermatophytosis in these patients varied from 10% to 90% [Table 2]. Extensive involvement with more than 40% BSA involvement was seen in 62% (23) of females and 33% (9) males and was found to be a significant factor determining chronicity in these patients (P < 0.05). The duration of the infection varied from 1 to 15 years with a mean duration of 3.14 years [Table 3]. There was no significant correlation between the duration of infection and mean BSA.

Table 2

Distribution of body surface area (BSA) affected by dermatophytosis

BSA (%)	Male	Female	Total
10-19	8	1	9
20-29	5	5	10
30-39	5	8	13
≥40*	9	23	32

*P<0.05

Table 3

Duration of chronic dermatophytosis and mean body surface area (BSA)

Duration (years)	Male	Female	Total (n=64)	Mean BSA (%)
1-2	6	12	18	49.4
2-3	8	13	21	45.7
3-4	8	6	14	38.9
4-5	4	2	6	37.5
6-10	-	3	3	46.6
11-15	1	1	2	42.5

Tinea corporis was the most common clinical type, seen in 46 patients (71.9%) [Figure 1]. It was the commonest type of infection in females (34, 91.9%). The most commonly affected site of tinea corporis was waist area in females and back in males. Tinea cruris was the most common infection in males (22, 81.5%) and was the second common clinical type next to tinea corporis in females (19, 51.4%). One patient presented with an inflammatory type of dermatophytosis. Tinea corporis with tinea cruris was the most common combination clinical type seen in 24 (55.8%) out of 43 patients with various clinical combinations [Table 4]. Tinea pedis was more common in males, whereas tinea axillaris, tinea faciei, tinea manuum, and tinea capitis were seen only in females. Both the females with tinea manuum as well as seven out of 10 patients (70%) with tinea pedis had involvement of nails. All 16 patients with KOH-proven nail involvement had a distal and lateral subungual type of onychomycosis. All the 20 nails were affected in two (12.5%) patients.

Figure 1

Frequency distribution of clinical types of dermatophytosis

Table 4

Distribution of combination of various clinical types of dermatophytosis

Clinical type	Male	Female	Total (n=64)
Tinea corporis	4	6	10
Tinea cruris	9	2	11
Tinea corporis and tinea cruris	3	9	12
Tinea corporis and tinea axillaris	0	4	4
Tinea corporis, tinea cruris, and tinea axillaris	0	4	4
Tinea corporis and tinea unguium	0	3	3
Tinea corporis, tinea manuum, and tinea unguium	0	2	2
Tinea corporis and tinea faciei	0	1	1
Tinea corporis, tinea faciei, and tinea capitis	0	2	2
Tinea corporis, tinea cruris, and tinea pedis	2	0	2
Tinea corporis, tinea cruris, tinea pedis, and tinea Unguium	3	3	6
Tinea cruris and tinea pedis	1	1	2
Tinea cruris and tinea unguium	5	0	5

Systemic and cutaneous associations

Various systemic and cutaneous conditions were seen in some of these patients with chronic dermatophytosis [Table 5]. Bronchial asthma was the most frequent systemic association observed in this study (20 patients, 31.3%) followed by diabetes mellitus in 13 (20.3%) patients. Cutaneous disorders other than tinea infection were found in 18 patients. A total of 22 patients (34.4%) were on long-term steroids or other immunosuppressive agents.

Table 5

Distribution of various systemic and cutaneous conditions in patients with chronic dermatophytosis

Systemic disorder	Total	Cutaneous disorder	Total
Bronchial asthma	20	Hansen’s disease	3
Diabetes mellitus	13	Palmoplantar psoriasis	3
Systemic hypertension	4	Icthyosis	3
Renal transplant recipient	2	Oral candidiasis	3
HIV*	2	Pemphigus vulgaris	2
Hypothyroidism	2	Keratolysis punctate	2
MCTD†	1	Erythrasma	2

*HIV=Human immunodeficiency virus infection. †MCTD=Mixed connective tissue disorder

Laboratory investigations

Twenty-six (40.6%) patients were found to have eosinophilia with an absolute eosinophil count of more than 450 cells/mm3. Among them, 16 patients (61.5%) had atopy or bronchial asthma. Out of 64, 27 patients (42%) were found to have elevated serum IgE levels (>400 IU/mL), of which 18 patients (66.7%) had bronchial asthma or atopy. Two female patients with asthma had very high levels of serum IgE (>1,200 IU/mL).

Sixty out of the 64 (93.8%) patients had KOH positivity of skin scrapings showing long hyaline septate branching hyphae with or without arthrospores. Dermatophytes were visualized in KOH mount in all the 16 patients with nail involvement. Out of the 64 culture specimens, 28 (43.8%) showed culture positivity for dermatophyte isolation. Among the 28 isolates, T. mentagrophytes was the most frequent species isolated in 13 patients (46.4%) [Figure 2], followed by T. rubrum in 11 (39.3%) patients [Figure 3], and T. tonsurans (7.1%) [Figure 4] and T. verrucosum (7.1%) [Figure 5] in two patients each.

Figure 2

Trichophyton mentagrophytes: (a) White downy colony with yellow reverse. (b) Microscopic morphology: spiral hyphae with microconidia. (c) Numerous macroconidia

Figure 3

Trichophyton rubrum: (a) White cottony colony with red reverse. (b) Microscopic morphology: microconidia in enthyrse and engreppe distribution

Figure 4

Trichophyton tonsurans: (a) Wrinkled colony with brown reverse. (b) Microscopic morphology: intercalary and terminal chlamydoconidia with match stick microconidia

Figure 5

Trichophyton verrucosum: (a) Gray-colored heaped up colony. (b) Microscopic morphology: chains of chlamydoconidia

T. rubrum was the most common species isolated in males (43.8%), whereas a majority of the isolates from females (66.7%) were T. mentagrophytes. T. tonsurans as well as T. verrucosum were isolated only from males who were farmers by occupation. The distribution of species isolated with respect to the clinical type is shown in Table 6. There was no statistically significant correlation between the clinical type and species isolated.

Table 6

Distribution of clinical types with dermatophyte species

Clinical type	T. rubrum	T. mentagrophyte	T. verrucosum	T. tonsurans	Culture negative
Tinea corporis	-	2 (F*)	-	-	8
Tinea cruris	1 (M†)	1 (F)	-	-	9
Tinea corporis and tinea cruris	3 (M)1 (F)	2 (M)	2 (M)	2 (M)	2
Tinea corporis and tinea axillaris	1 (F)	2 (F)	-	-	1
Tinea corporis, tinea cruris, and tinea axillaris	1 (F)	1 (M)1 (F)	-	-	1
Tinea corporis and tinea unguium	-	1 (F)			2
Tinea corporis, tinea manuum, and tinea unguium	-	-			2
Tinea corporis and tinea faciei	-	-			1
Tinea corporis, tinea faciei, and tinea capitis	-	1 (F)	-	-	1
Tinea corporis, tinea cruris and tinea pedis	-	1 (M)	-	-	1
Tinea corporis, tinea cruris, tinea pedis and tinea unguium	2 (M)1 (F)	-	-	-	3
Tinea cruris and tinea pedis	-	1 (M)	-	-	1
Tinea cruris and tinea unguium	1 (M)	-	-	-	4
Total	7 (M)4 (F)	5 (M)8 (F)	2 (M)	2 (M)	36

*Female, †Male. T=Trichophyton

Discussion

In this study, the most affected age-group was between 51 and 60 years, closely followed by 31 to 40 years with a mean age of 44.5 years. Males in the sixth decade and females in the fourth decade were more affected. The trends in age and sex demographics reflected in few other studies on patients with chronic dermatophytosis have been compared in Table 7.[46789] The higher number of females diagnosed with chronic dermatophytosis may be attributed to the neglect in proper self-care among the females, occlusive clothing over waist area due to the traditional Indian female attire known as sari, and prolonged household work in hot and humid climate resulting in excessive sweating that provides a contusive milieu for germination of dermatophytes.

Table 7

Clinico-demographic characteristics of patients with chronic dermatophytosis in various studies

Reference	Present study (n=64)	Jamuna et al.[6] 2019, India (n=72)	Zachariah et al.[7] 2017, India (n=50)	Karthika et al.[8] 2016, India (n=60)	Prasad et al.[10] 2005, India (n=75)	Sentamilselvi et al.[4] 1997, India (n=2,276)	Khosravi et al.[9] 2012, Iran (n=163)
Most common age-group andsex	51-60 years (31%)Females (58%)	21-30 years (37.5%)Males (60%)	31-40 years (32%)Females (66%)	30-40 years (31.6%)Females (60%)	NA*	20-30 yearsMales (77%)	30-44 years (28.8%)Males (58.9%)
Average duration of infection (years)	3.14	NA	NA	7.35	NA	4.1	8.7
Asthma prevalence (%)	31.3%	NA	30%	16.6%	13.3%	7.3%	25%
Diabetes prevalence (%)	20.3%	NA	22%	30%	17.3%	7%	8%
KOH positive (%) and Culture positive (%)	94%	77.5%	80%	83%	88%	100%	NA
	43.8%	56%	68%	52%	41%	57.6%
Most common species isolated (%)	T. mentagrophytes (46.4%)	T. mentagrophytes (50.8%)	T. rubrum (41%)	T. rubrum (46%)	T. rubrum (42%)	T. rubrum (74.6%)	T. mentagrophytes (73%)

*NA=Data not available. T=Trichophyton

The most common clinical types in this study were tinea corporis in females and tinea cruris in males. The commonest site involved in tinea corporis was the back in men and the waist in women, which is in accordance with the findings of Sentamilselvi et al.[4] and Karthika and Balaji.[8] The most common site of infection was soles in the study by Hay.[2] But tinea pedis is relatively less prevalent in India compared with the Western world possibly due to the infrequent wearing of closed footwear. However, it is more common in Indian males compared with females again due to the above reason. Tinea axillaris was seen predominantly among the females. This pattern of distribution may be attributed to a highly humid environment, the occlusive dressing pattern of the patients, along with excessive sweating and moisture resulting in repeated infection with dermatophytes.

Tinea unguium was seen in 25% patients in the study group. This is in accordance with the study by Prasad et al.[10] who observed onychomycosis to be present in 28% patients with chronic dermatophytosis, thus proving nail involvement to be a statistically significant factor associated with chronicity. Khosravi et al.[9] documented tinea unguium in 29.4% patients, whereas 32% had onychomycosis in the study by Jamuna et al.[6]

Bronchial asthma was the most common disease associated with chronic dermatophytosis, found in 31.3% patients, which is in accordance with the findings by Hay[2] and Svejgaard[11] who reported 32% and 57%, respectively. Chronic dermatophytosis was found to be threefold more frequent in atopic individuals. In similar studies from the Indian subcontinent, prevalence of atopy in patients with chronic dermatophytosis varied from 7.3% (Sentamilselvi et al.[4]) to 30% (Zacharia and Kunjukunju) [Table 7].[7] It has been postulated by Wood Folk and Hurliman[12] that absorption of fungal allergen may result in bronchial hyperactivity with late-onset intrinsic-type asthma.

Diabetes mellitus was the second most frequent systemic association with a prevalence of 20.3%. Similar findings were reported in other studies on chronic dermatophytosis also [Table 7]. However, no such correlation between diabetes and dermatophytosis (not essentially chronic dermatophytosis) was noted in the studies by Lugo-Somolinos and Sanchez,[13] Buxton et al.[14] and Romaro et al.[15]

Ichthyosis and psoriasis were found in three patients each (4.7%) in this study, which is similar to the observation by Hay[2] (4%) and Zacharia and Kunjukunju (8%).[7] However, Sentamilselvi et al. reported a much higher association of 25%.[4] Local factors are supposed to contribute to the infection rather than any immunological alteration in these patients. The retained keratin often acts as a nidus for the infective agent in patients with keratinization disorders such as ichthyosis.

A total of 22 patients (34.4%) were on systemic steroids for various indications, which is much higher than that observed by Khosravi et al.[9] (8.6%) or Hay[2] (2%). Chronic steroid use was reported to be associated with recurrent infection by Rebell in 1996.[16] It has been suggested that high levels of steroid may increase the thickness of stratum corneum and delay the desquamation resulting in the persistence of infection.[16] It is important to note that topical steroid abuse did not emerge as a significant factor responsible for chronicity in this study, unlike the recent trend.

Elevated serum IgE levels were seen in 27 (42.2%) patients. Khosravi et al.[9] also reported that 44.2% of patients with chronic dermatophytosis presented with elevated IgE levels. Hay[2] reported 8% patients to have raised IgE levels in his study. Eosinophilia along with elevated IgE levels was reported to be associated with chronic dermatophytosis by Martin and Elewski[17] and Ward et al.[18]

KOH preparation was positive in 94% of patients, whereas positive culture was obtained in 43.8% cases. The corresponding figures reported in the various studies are depicted in Table 7.

T. mentagrophytes was the most common species isolated in this study followed by T. rubrum. However, this is in contrast to numerous previous studies in which T. rubrum was the most common etiological agent followed by T. mentagrophytes [Table 7]. T. rubrum was the species isolated from patients with HIV as well as renal transplantation. Predominance of T. mentagrophytes in this study may signify a changing pattern in the spectrum of chronic dermatophytosis, which warrants further studies. At present, various factors such as global warming, thermos tolerance of T. mentagrophytes, and rampant abuse of topical corticosteroids have been postulated to be responsible for the emergence of T. mentagrophytes. It would be worthwhile to note that 34.4% of the patients in this study were on systemic steroids. There is a dire need at present to study the clinicomycological aspects of chronic dermatophytosis, host immunity, and the effect of corticosteroids on dermatophytes.

T. tonsurans was isolated from 7.1% of patients and has been reported in few other studies also in a lesser proportion of patients.[24678] T. verrucosum was isolated from two male patients (7.1%) from rural area who were farmers by occupation with a history of contact with cattle. One of them had inflammatory type of dermatophytosis, whereas the second patient had noninflammatory lesions. Similar reports of T. verrucosum have been made by Zacharia and Kunjukunju[7] and Karthika and Balaji.[8]

Our study has the limitation of the sample size being small and not substantial without a control group, and hence studies with larger sample size from various parts of the country are required to further substantiate the changing trend of dermatophytes causing chronic dermatophytosis. This was a descriptive study with focus only on the clinicomycological aspects without performing antifungal susceptibility tests and therefore treatment options need to be evaluated in prospective studies.

Conclusion

In this study on chronic dermatophytosis, extensive area of involvement, long-term use of systemic steroids, atopy, and diabetes were associated with chronicity. T. mentagrophytes was the most common causative species followed by T. rubrum, reflecting the changing trend in the etiology of chronic dermatophytosis. There is a gaping void of consensus in the management of chronic dermatophytosis, and subsequently various oral antifungals in higher doses or for longer duration are being used to tackle the infection in these patients.[1920] Well-designed case–control studies comparing different antifungals in various doses and durations, including antifungal susceptibility testing and counseling patients regarding strict adherence to the general measures, are the need of the hour in this context for the appropriate management of chronic dermatophytosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.