Epidermophytosis and dermatophytid reaction during onychomycosis: a report of two cases

¹Parasitology and Mycology Laboratory, Moulay Ismail Military Hospital of Meknes, Morocco, ²Faculty of Medicine and Pharmacy of Rabat, Mohamed V University, Morocco, ³Faculty of Medicine, Pharmacy and Dentistry of Fez, Sidi Mohamed Ben Abdelah, Morocco

^&Corresponding author
Kamal El Azzaoui, Parasitology and Mycology Laboratory, Moulay Ismail Military Hospital of Meknes, Morocco

Introduction    

Dermatophytoses are common superficial fungal infections caused by keratinophilic fungi belonging to the family Arthrodermataceae. The three main genus implicated in human infections are Trichophyton, Microsporum, and Epidermophyton. The clinical manifestations of dermatophyte infections vary according to the causative species. Zoophilic and geophilic species generally cause more inflammatory lesions than anthropophilic species [1]. A dermatophytid is an immunological reaction to fungal antigens. Antigen release is often triggered by the initiation of antifungal therapy, although it may also occur spontaneously. The clinical presentation is variable and may include pustular, psoriasiform, eczematous, edematous, or vesiculobullous dermatosis [2]. The coexistence of onychomycosis and secondary cutaneous lesions often presents a diagnostic challenge, particularly when distinguishing an active dermatophyte infection from a dermatophytid reaction. In this context, the present study highlights the role of mycological examination in the differential diagnosis and in guiding targeted therapeutic management.

Patient and observation     

Both patients presented to the Department of Parasitology and Mycology at Moulay Ismail Military Hospital in Meknes for mycological examination of an onychopathy.

Case 1

Patient information: the patient was a 55-year-old woman with psoriatic arthritis associated with disabling deformities affecting several fingers. She was receiving anti-TNF therapy and immunosuppressive treatment with prednisone and methotrexate, as well as the nonsteroidal anti-inflammatory drug (piroxicam) and a central muscle relaxant (Tolperisone).

Clinical findings: clinical examination revealed findings suggestive of toenail onychomycosis (two toes of the right foot and four toes of the left foot) with hyperkeratosis and xanthonychia. The patient also presented with irregularly bordered erythematous scaly plaques on both lower legs (approximately 20 cm in diameter), as well as lesions in the axillary regions and on the arms (approximately 5 cm in diameter) (Figure 1).

Timeline of current episode: the patient's symptoms began approximately two months prior to presentation, with the development of erythematous skin lesions on both lower limbs, in the axillary regions, and on the arms, which subsequently evolved into a scaly appearance. These lesions were preceded, approximately one year earlier, by toenail onychomycosis. The patient reported failure of a traditional herbal treatment based on Marrubium vulgare.

Diagnostic assessment: direct microscopic examination of the samples, using a 10% potassium hydroxide (KOH) preparation, revealed the presence of mycelial filaments in samples collected from the toenail and from the cutaneous lesions on the legs and arms (Figure 2). Cultures of the samples on Sabouraud agar and Sabouraud agar supplemented with cycloheximide, incubated at 37°C, resulted in the isolation of Trichophyton interdigitale after 7 days. Macroscopically, T. interdigitale colonies were initially off-white with a fluffy appearance and subsequently became powdery. A brown pigment was observed on the reverse side of the colonies (Figure 3). Microscopically, the colonies showed articulated filaments with right-angle branching, spiral hyphae, and numerous round microconidia arranged in clusters, as well as smooth-surfaced, club-shaped macroconidia (Figure 4). The urease test was positive (Figure 5).

Diagnosis: based on the patient's medical history, clinical presentation, and mycological findings, the diagnosis of secondary epidermophytosis to onychomycosis caused by Trichophyton interdigitale was established.

Therapeutic interventions: epidermophytosis was treated with topical isoconazole 2%, applied twice daily for 2 weeks, while onychomycosis was treated with terbinafine 250 mg once daily for 6 months.

Follow-up and treatment outcome: the patient showed a favorable clinical response to treatment, with progressive improvement of the cutaneous lesions and regression of toenail onychomycosis.

Patient perspective: the patient was satisfied with the improvement in her cutaneous lesions and toenail onychomycosis and reported an overall improvement in her quality of life.

Informed consent: it was obtained from the patient for the use of her clinical photographs and clinical data for publication and academic research purposes.

Case 2

Patient information: the patient was a 41-year-old man receiving treatment for asthma and circulatory disorders.

Clinical findings: clinical examination revealed vesicular and scaly lesions on the plantar surface of the right foot, eczematous lesions on both legs, and interdigital intertrigo associated with hyperkeratosis and chloronychia of the right great toenail (Figure 6).

Timeline of current episode: the patient's symptoms began approximately eight years earlier with erythematous, vesicular, intensely pruritic skin lesions on both legs that later evolved into an eczematous eruption. This cutaneous eruption was preceded, 18 months earlier, by untreated toenail onychomycosis. The patient reported failure of treatment for the recurrent leg lesions with methotrexate (15 mg administered subcutaneously once weekly), combined with a topical corticosteroid (clobetasol propionate 0.05%) and an emollient preparation containing glycerin, petrolatum, and paraffin oil, administered for three months.

Diagnostic assessment: direct microscopic examination of a 10% potassium hydroxide (KOH) preparation of the toenail sample was positive, showing mycelial filaments, whereas skin scrapings from the other associated lesions were negative. Culture on Sabouraud agar and Sabouraud agar supplemented with cycloheximide (Actidione), incubated at 37°C, resulted in the isolation of Trichophyton rubrum from the toenail sample, whereas cultures of skin scrapings from the other lesions remained negative. Macroscopically, T. rubrum colonies were whitish and fluffy. On the reverse, a red pigment was observed on day 20 of incubation. Microscopic examination revealed a few pyriform microconidia arranged in an acradium pattern, along with rudimentary lateral fusiform structures (Figure 7). The urease test was negative.

Diagnosis: based on the patient's medical history, clinical presentation, and mycological findings, a diagnosis of dermatophytid reaction secondary to Trichophyton rubrum toenail onychomycosis was established.

Therapeutic interventions: dermatophytid was treated with topical betamethasone 0,05% while onychomycosis was treated with terbinafine 250 mg, for 6 months.

Follow-up and treatment outcome: the patient showed a favorable response to treatment, with progressive resolution of the dermatophytid reaction and improvement of toenail onychomycosis.

Patient perspective: the patient was satisfied with the improvement of his recurrent skin lesions and reported an overall improvement in his daily well-being.

Informed consent: it was obtained from the patient for the use of his clinical photographs and clinical data for publication and academic research purposes.

Discussion     

Dermatophytoses are common superficial fungal infections in humans and represent a frequent reason for consultation in dermatology and medical parasitology. Their clinical presentation is polymorphic and may sometimes be accompanied by distant immunoallergic manifestations, known as dermatophytids. Dermatophyte infection begins with the adhesion of arthroconidia to the host epidermis through specific fungal surface proteins [3]. For example, T. rubrum adheres to epithelial cells through carbohydrate-specific adhesins expressed on the surface of microconidia, whereas T. mentagrophytes relies on fibrillar projections for adhesion [4]. The arthroconidia then resume metabolic activity and develop into hyphae. These hyphae invade the stratum corneum through germ tubes and secrete various keratinases that degrade keratin into peptides and amino acids, which dermatophytes utilize as nutrients for growth and reproduction [5].

Dermatophytids are delayed-type hypersensitivity reactions (type IV) resulting from the opsonization of dermatophyte antigens released at the site of infection by host antibodies. These antigens are subsequently presented to sensitized T helper 1 (Th1) lymphocytes, which trigger distant cutaneous manifestations through the release of cytokines. These immunoallergic reactions occur during periods of maximal release of dermatophyte antigens, particularly during the acute phase of infection, approximately 10 days after inoculation, as well as following the initiation of antifungal therapy, with a mean onset of approximately 13 days after treatment [6]. Epidermophytosis may be caused by various dermatophyte species and can affect any area of the body. The lesions typically present as erythematous, scaly plaques that expand rapidly in a centrifugal pattern. They are initially round but progressively become annular, with an inflammatory raised border associated with scaling or vesicles. The main differential diagnoses include nummular eczema, eczematids, and pityriasis rosea (Gibert's pityriasis rosea). Dermatophytids are allergic cutaneous manifestations occurring at sites distant from the primary fungal infection. They most commonly affect the hands, where they typically present as a dyshidrotic eruption [1]. Their clinical presentation is variable and may include psoriasiform, eczematous, edematous, vesiculobullous, or pustular lesions [2].

The diagnosis of epidermophytosis is primarily based on a positive mycological examination, consisting of the detection of mycelial filaments, sometimes associated with arthroconidia, on direct microscopic examination, together with the isolation of the causative dermatophyte in culture. In contrast, the diagnosis of dermatophytids relies on the presence of a documented dermatophyte infection, combined with negative mycological examination of the secondary cutaneous lesions and their regression following treatment of the underlying dermatophytosis. Delayed-type hypersensitivity testing with trichophytin may be positive but is not essential in routine clinical practice. The discordance between the mycological findings from the primary infection and those from the secondary lesions represents a major diagnostic clue and underscores the importance of systematically sampling the suspected primary site of infection, particularly the nails [7].

The treatment of these two conditions differs. Epidermophytosis is generally treated with topical antifungal agents for 4-6 weeks. Antifungal creams should be applied directly to the lesions and extended at least 1-2 cm beyond the affected area. Oral terbinafine (250 mg once daily) or itraconazole (200 mg once daily) for 2-3 weeks is recommended in cases of multiple lesions, infection involving vellus hair, recurrent or chronic infection, or failure to respond to topical therapy [8]. Dermatophytids are treated with antifungal therapy directed at the primary infection, combined with topical or systemic corticosteroids. Topical corticosteroids such as betamethasone dipropionate or clobetasol propionate may be applied once daily for 7-14 days. Antihistamines, such as cetirizine (10 mg orally once daily), may be used to relieve pruritus. Emollients and wet compresses may also be recommended [6]. The evolution of epidermophytosis under antifungal therapy is generally favorable, with progressive clinical improvement and healing within a few weeks. However, the emergence of antifungal resistance may lead to persistent or recurrent forms, requiring diagnostic reassessment and more prolonged or tailored treatment. Regarding dermatophytids, the evolution is also generally favorable. However, it has been reported that the allergic eruption may persist even after eradication of the underlying dermatophyte infection [9]. These two cases highlight the importance of systematically investigating for onychomycosis in patients presenting with atypical inflammatory skin lesions and underscore the necessity of performing a rigorous mycological examination, which plays a crucial role in guiding both diagnosis and treatment.

Limitation: the absence of clinical photographs taken during and after treatment, which were not provided by either patient, represents a limitation of this study.

Conclusion     

The distinction between active dermatophytosis and dermatophytid reaction relies on the correlation of clinical and mycological findings. These two cases highlight the essential role of mycological examination in establishing the diagnosis and guiding appropriate patient management.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Data collection and literature review: Kamal El Azzaoui, Sanaa Lharti, Khalid Aboulhassane and Mourad Belaouni. Manuscript drafting: Kamal El Azzaoui. Revision of the manuscript: Mohammed Er-Rami and Mourad Belaouni. All the authors have read and approved the final version of this manuscript.

Figures     

Figure 1: A) onychomycosis of the toenail; B,C) cutaneous lesions of the arm and leg

Figure 2: A) mycelial filaments observed in the nail sample and in skin sample from the leg and arm; B, C) on direct examination with potassium hydroxide (KOH) preparation (x40 magnification)

Figure 3: A, B) colonies of Trichophyton interdigitale on Sabouraud agar without; C) front and reverse views) and on Sabouraud agar with cycloheximide

Figure 4: microscopic examination of a T. interdigitale colony in lactophenol blue at x100 magnification

Figure 5: positive urease test reaction of T. interdigitale

Figure 6: A) clinical appearance of onyxis of the great toenail; (B,C) lesions on the legs and plantar surface of the foot

Figure 7: A) mycelial filaments observed in the nail sample by direct examination with potassium hydroxide (KOH) preparation (x40 magnification); B) colonies of Trichophyton rubrum on Sabouraud agar (front and reverse views); C) colonies of Trichophyton rubrum on Sabouraud agar with cycloheximide; D) microscopic examination of a T. rubrum colony in lactophenol blue at x40 magnification

References