|Year : 2017 | Volume
| Issue : 3 | Page : 12-18
Emerging atypical and unusual presentations of dermatophytosis in India
Sunil Dogra1, Tarun Narang2
1 Member, IADVL Task-force Against Recalcitrant Tinea (ITART); Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||10-Oct-2017|
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
In the recent past, there has been an alarming rise in patients presenting with atypical clinical types of dermatophytosis. These patients require prolonged treatment with systemic and topical antifungal agents. In majority of patients, close household contacts are affected. Frequent relapses and extensive disease affect the quality of life of the patient significantly. The emergence of such a challenging scenario is attributed to complex interplay of host, environment, and agent factors. The change in prevalence of dermatophytes causing the disease; host factors such as comorbidity and immunosuppression; and hot and humid climate, lifestyle changes, and poor hygiene are responsible for atypical dermatophytosis. Several atypical clinical types such as psoriasis-like, eczematous dermatitis-like, seborrheic dermatitis-like, and rosacea-like have been reported. Hence, dermatophytosis has been suggested to be included in the list of great imitators. The collaborative effort involving dermatologists, microbiologists, and public health professionals is required to address this emerging public health problem.
Keywords: Atypical presentation, dermatophytosis, great imitator
|How to cite this article:|
Dogra S, Narang T. Emerging atypical and unusual presentations of dermatophytosis in India. Clin Dermatol Rev 2017;1, Suppl S1:12-8
| Evolving Indian Scenario|| |
Dermatophytosis has been the most common cause of superficial fungal infections in dermatology clinics throughout the world. However, in the past 5–7 years, there is an alarming rise in overall number of case and increasing proportion of difficult to treat chronic and recurrent dermatophytosis in India. Patients are presenting with widespread, atypical, extremely symptomatic lesions of tinea corporis, facei, cruris, pedis, and capitis which require prolonged duration of therapy. Subsequently, patients suffer from frequent relapses within few days to weeks of stopping treatment. Majority of these patients have household contacts and sometimes the entire family is affected. This has led to significant impairment in quality of life. It not only adds to huge morbidity but also puts an enormous financial burden because of frequent and prolonged courses of antifungal therapy. While this phenomenon of recalcitrant dermatophytosis at present is seen, particularly, in the Indian subcontinent, it is likely that such an epidemiological trend may soon drift to the Western world. Management of recurrent and chronic dermatophytosis has become a great therapeutic challenge for dermatologists. Dermatophytosis is now standing in a row along with traditional difficult to treat dermatoses such as psoriasis, vitiligo, pemphigus, and erythrodermas. What was considered to be the most trivial cutaneous infection to treat has become most stubborn to manage.,
The antifungal drug market in India has grown by more than 100% in recent years following the epidemic-like situation of dermatophytosis in the country. Almost every other pharmaceutical company has started marketing various antifungals drugs. The quality and bioavailability of some of the antifungal drugs by mushrooming companies are feared to be substandard which may add to this growing menace of difficult to treat dermatophytosis. Recurrent dermatophytosis is the topic of discussion in almost every social media groups of Indian dermatologists. In recent years, in almost all Continued Medical Education programs and Conferences in India, there are dedicated sessions on dermatophytosis, and two theme-based conferences are planned in year 2017. While this enigmatic form of dermatophytosis started around 2010 in India, the proportion and severity of such forms of clinical disease have further worsened in the past 2–3 years. Depending on clinical settings, almost 15%–20% of patients in dermatology outpatient departments and clinics present with recalcitrant dermatophytosis. Children including infants with facial involvement and adults with tinea capitis have become a frequent clinical presentation. Treatment of widespread tinea in pregnant women has become a dermatologist's nightmare. With fast-growing problem in the country, dermatologists are facing new therapeutic challenges such as antifungal therapy in patients with comorbidities such as diabetes, hypertension, heart disease, and chronic liver and kidney disorders, and clinically significant drug interactions associated with concomitant management of these disorders. Many patients resorting to faith healers, quacks, indigenous medicines, and religious beliefs such as holy bath is worsening the problem.
Although the problem of recalcitrant dermatophytosis is growing leaps and bounds in India, there is a lack of substantial published epidemiological, clinical, and laboratory research in this field. Many research projects, postgraduate thesis, and collaborative works are underway to elucidate the factors that could have lead dermatophytosis to this crossroad in India. It is to be explored by meticulous studies whether the “clinical resistance,” a phenomenon of rising MIC to antifungal drugs, is due to various factors or a march of dermatophytes toward the development of “antifungal drug resistance.” Nevertheless, the concept of antifungal drug resistance and in vitro methods to prove it in dermatophytes are far more complex than Candida and invasive molds. The problem is compounded by the fact that laboratory diagnosis of dermatophytosis has been generally a neglected area in clinical practice, and hence the expertise available in the country for advance molecular diagnosis and antifungal drug susceptibility in dermatophytosis is very limited.,
| The Host, Pathogen, and Environmental Factors|| |
The current scenario is frustrating both for the physicians and the patients. There are only a few published studies that have tried to explore this growing menace in India. However, the available literature indicates that the emerging atypical and unusual manifestations can be due to a complex interplay of host, agent, environmental, or pharmacologic factors. These factors include dysregulation in host defensive immune system, biofilms, and increasing MIC of antifungal drugs, atopy, or selective anergy in host, climatic condition or overcrowding, migration, urban clothing patterns, and poor hygiene.,
There is a constant evolution of the dermatophytes influenced by the geographic and socioeconomic conditions. About one century ago, Epidermophyton floccosum, Microsporum audouinii, and Trichophyton schoenleinii More Details were the major pathogens causing dermatophytosis, but their frequency decreased, and now they are limited to some less developed countries. Now, Trichophyton rubrum has become the leading pathogen of skin and nail fungal infections followed by Trichophyton mentagrophytes. Similar trends are also being observed in epidemiological studies across India where T. rubrum and T. mentagrophytes are reported as the most common pathogens causing dermatophytosis. These changes in the prevalence of causative organisms/species can be due to local socioeconomic conditions and cultural practices. Different types of dermatophyte pathogens have been associated with multiple unusual clinical manifestations such as the circumscribed scleroderma, crusty circular plaques, white paint-like dots, psoriasis-like lesions, or dystrophic onychomycosis due to Microsporum gypseum infection. In their study of atypical dermatophytosis, Atzori et al. reported T. rubrum, T. mentagrophytes, and Microsporum canis as the most common isolated organisms. Other dermatophytes that have been reported to be responsible for atypical manifestations are Trichophyton interdigitale, Trichophyton tonsurans, Trichophyton verrucosum, and M. gypseum.
Besides the species and invasive capacity of dermatophytes, the clinical manifestations of dermatophytosis may also depend on host factors such as site of invasion, physiological variation of host skin barrier, age of patient, obesity, immunosuppressive state, and acquired conditions such as excessive washing or sun exposure. Anatomical characteristic of affected area which includes the presence of skin folds, sebaceous glands, variable thickness of the corny layer, and vellus hair follicle involvement also affects the typical centripetal progression and favors inflammation and crusting.
The dermatophytic clearance from the skin is secondary to the activation of cell-mediated immunity (CMI) and is Th1/Th17 dependent. Immune dysregulation with skewed immune response toward Th2 cytokines with high levels of IgE and IgG4 antibodies may be responsible for some of these atypical, chronic, or unusual clinical forms. Sometimes, the comorbid conditions of host-like psoriasis, atopy, and diabetes may be the cause of this immune dysregulation and the subsequent clinical manifestation of tinea., The exact mechanism involved in this defective shift of immunity and selective absence of CMI with respect to dermatophytosis is not well understood. Defective phagocytosis and processing of the fungal hyphae by the macrophages, neutrophils, or decreased complement levels may be another factor which could lead to more severe deep dermatophytosis. Caspase recruitment domain-containing protein 9 (CARD9) gene mutation, which is involved in the regulation of multiple downstream pathways having antifungal response, is noted to be associated with severe fungal infections of varied clinical presentations ranging from deep dermatophytosis to recurrent dermatophytic infection of skin and nails. There is an increased prevalence associated with the disorders of keratinization such as ichthyosis vulgaris where retained keratin often acts as a nidus for infection.
Dermatophytes are abundant in different ecological niches, and the three main sources of infection by dermatophytes are humans, animals, and soil. Dermatophytes have the ability to utilize keratin from human and animal tissues, or debris from dead animal sources found in soil, such as feathers, skin, or nails. Dermatophytes from all these three sources can infect humans through direct or indirect contact, causing dermatophytoses manifested in different clinical entities. Transmission of dermatophytosis occurs almost exclusively through indirect contact, as the dermatophytes initially contaminate the patients' environment and subsequently facilitates the spread of infection to others. Dermatophytes are found universally; however, the relative prevalence of dermatophytoses caused by different dermatophytes may vary in different geographic areas according to climatic conditions or lifestyle. Hot and humid climate, low socioeconomic status, overcrowding, sharing of clothes and footwear, poor hygiene and sanitary conditions, and migration of population are also some predisposing environmental factors in Indian scenario which may be responsible for the increasing chronic and recurrent forms of dermatophytosis.
In addition to the above-mentioned factors, other causes could be incorrect diagnosis, immunosuppression, and suboptimal dose or duration of therapy. Reinfection from the contacts or fomites may also be a contributing factor, especially for chronic/recurrent dermatophytosis who have multiple affected family members.
However, all the above host, pathogen, and environmental risk factors are well known [Table 1], what has led to this fast-growing epidemic-like proportion of recurrent and chronic forms of difficult to treat tinea is an enigma posing a great management challenge to dermatologists.
|Table 1: The host, pathogen, and environmental factors for atypical and unusual tinea manifestations|
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| Atypical and Unusual Clinical Presentations of Tinea|| |
There are cases with unusual manifestation of tinea which are termed as atypical tinea though it is not synonymous with tinea incognita. The term ''tinea incognita'' is generally used for steroid modified cases of dermatophytosis although subsequent reports have shown tinea incognita with tacrolimus and pimecrolimus as well. Atypical tinea can be seen in immunocompetent patients who are not using any topical and systemic medicaments such as corticosteroids.
Cutaneous dermatophytosis may sometimes mimic other dermatoses and multiple atypical clinical varieties have been reported which include erythema multiforme-like, seborrheic dermatitis-like [Figure 1], lupus erythematosus-like [Figure 2], dermatitis herpetiformis-like, rosacea-like, eczematous dermatitis-like [Figure 3], psoriasis-like [Figure 4], impetigo-like, and polymorphous light eruption-like [Table 2]. Although these are more common in immunocompromised individuals, they can be seen in immunocompetent persons as well. Such clinical presentations of tinea though rarely reported in literature are now being routinely seen in India. Tinea has now qualified for the category of great mimicker similar to syphilis, sarcoidosis, and mycosis fungoides. Besides, the classical erythematous annular plaque with a scaly, centrifugally advancing borders, the dermatophyte infections can sometimes present in atypical morphologies such as pyoderma, bullous [Figure 5], eczematous, purpuric, or nodular lesions., There are few case series of atypical tinea infection from different countries. In one of such reports, Atzori et al. observed eczema-like tinea as the most common atypical manifestation of tinea. Among patients with atypical tinea lesions, 20% had previous cutaneous illnesses such as atopic dermatitis, contact dermatitis, lichen planus, and psoriasis. Asthma, allergic rhinitis, intestinal inflammatory illnesses, and chronic renal insufficiency were present in 15%, and 23% of them had not applied topical corticosteroids or taking on systemic therapy that could have modified primary morphology. Dermatophytes are generally confined to the stratum corneum or the epidermis, and the normal defenses that prevent the deeper invasion of dermatophytes are physical barriers (epidermal keratinization, epidermal keratinocyte turnover, pH, fatty acids from sebaceous glands, and body temperature), innate and adaptive immunity, and serum components, but rarely they may invade the dermis and cause granulomatous inflammation which may manifest as nodules.
|Figure 2: Tinea lesions on the malar area resembling lupus erythematosus|
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|Table 2: Atypical manifestations, causative organisms and proposed mechanisms for atypical variants of tinea infection|
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Deep dermatophytosis is a rare clinical entity characterized by infection of the dermis, subcutis, and internal visceral organs. It is characterized by nodular lesions with an indolent course, an association with superficial fungal infection [Figure 6], and the absence of hair follicle involvement. However, deep dermatophytosis is a separate entity, distinct from Majocchi's granuloma [Table 3]. It is generally seen in patients who are immunocompromised due to systemic diseases such as systemic lupus erythematosus, diabetes, HIV, or who are receiving immunosuppressants for the management of these autoimmune diseases. In extremely rare cases such as specific genetic predisposition or specific immune defects, lymphatic spread has been documented, causing mycetoma/pseudomycetoma and even dissemination to extracutaneous sites. The growing population of immunocompromised patients has led to an increase in cases of deep (dermal/subcutaneous) dermatophytosis. Very rarely, they may cause a life-threatening infection by invading the lymph nodes. Primary immunodeficiency with a genetic origin is also recognized as a predisposition to deep dermatophytosis. The role of CARD9 gene mutations is being investigated in human antifungal immunity.,
|Figure 6: Nodular lesions of deep dermatophytosis in a renal transplant patient|
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|Table 3: Major differentiating features of Majochhi's granuloma and deep dermatophytosis|
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The diagnosis in these atypical cases can occasionally be missed by false-negative results from culture or even the KOH preparation. The presence of Periodic acid-Schiff-positive fungi in stratum corneum or hair follicles along with spongiotic dermatitis and neutrophils in the stratum corneum on histopathology is helpful in making the diagnosis in these difficult cases.
In addition to these atypical and emerging variants of dermatophytosis, another variant that is seen very frequently all over India is a recurrent infection or tinea recidivians. Steroid abuse in the form of combination formulations may be one of the most important predisposing factors in these resilient forms of dermatophytosis. It is being proposed that these manifestations are due to resilient organisms rather than resistant organisms. Resistance is characterized by nonresponsiveness to the treatment whereas the recidivans or the recurrent forms are characterized by response to the treatment initially and relapse within a week of stopping treatment or while on treatment. It is characterized by lesions appearing at the periphery of the healing patches [Figure 7]. The organisms isolated from these are T. rubrum and T. mentagrophytes. Unlike in the case of antibiotic resistance, there is little clinical correlation with in vitro antifungal drug susceptibility tests.
|Figure 7: Tinea recidivans: Appearance of lesions at the periphery of the old healed lesion|
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| Conclusions|| |
Fungal infections caused particularly by candida and invasive molds seem to have evolved and are now becoming the leading cause of mortality in sick patients admitted in hospital Intensive Care Units. Increasing prevalence of deep fungal infections and antifungal resistance is a global phenomenon. Superficial dermatophytosis too seems to be following the same pattern as we are seeing more and more cases of chronic and recurrent as well as atypical dermatophytosis. There is an urgent need to study the risk factors and predisposing conditions to effectively manage these cases. We also need epidemiologic studies to clarify the determinants of the trends and identify effective interventions that can reduce the morbidity associated with these dermatophytoses and the general public health burden of illness. These questions should be addressed jointly by clinicians, mycologists, and public health authorities at national and international levels.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3]
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