Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Healthcare e-Compendium
A joint initiative of DPSRU & DRSC
Author: Dr. R. P. Gupta
MBBS, MD, Dermatology, Skinnovation Clinics, Delhi
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Abstract
Fungal infection is the most prevalent skin disease globally and Antifungal treatment, either topical or systemic, is frequently used to treat it. Because of their focused therapy and less adverse effects, topical fungal therapy is generally recommended. Topical Ketoconazole solutions are used to stop the growth of fungus-like Dermatophytes, Candidiasis, and Pityrosporum. Nizral 2% formulated with micronized ketoconazole solution effectively stops the growth of fungus. The most well-known issue with fungal infections is recurrence. Use of prophylactic antifungal Nizral 2% solution wash for some period of time along with antifungal treatment minimizes the chances of recurrence. Nizral 2% is a global brand of ketoconazole shampoo solution, mentioned in most of the medical textbooks with a clinical legacy of 35 years.
Keywords: Fungal infections, Ketoconazole, Prophylaxis
Introduction
Fungal skin infections are the most well-known worldwide issue for skin health. There is a report of the prevalence of fungal infection affecting about 40 million people in developing and under-developed countries. The rate of occurrence of severe systemic fungal infections has increased significantly since the mid-20th century, mainly due to an increase in the number of patients with weak and compromised immune systems such as acquired immunodeficiency syndrome (AIDS) or post organ transplantation and chemotherapy. The extensive use of antibiotics added to the deteriorating of this image, prompting the establishment of fungal infections [1]. Fungal infection is classified into two types: Superficial and Deep. The superficial infection is only concerned with the stratum corneum of the epidermis (outer layer of the skin), shown in figure 1. Fungal infection extends deeper into the epidermis layer of skin called cutaneous mycoses. If a fungal infection grows further into the skin, it is known as “Subcutaneous mycosis” [2].
Figure 1: Fungal infections are commonly seen in the different layers of skin
Epidemiology
Among all fungal infections, superficial mycoses are the most frequent forms of human infections, affecting more than 20%–25% of the world's population [3]. It is also estimated that 30%–70% of adults are asymptomatic carriers of these pathogens [4]. Dermatophytes species are categorized into zoophilic, geophilic, or anthropophilic, depending on their primary habitat (animals, soil, or humans, respectively). 30% of human dermatophytoses occur due to zoophilic species and usually cause acute inflammation. Anthropophilic species represent about 70% of infections on these hosts, causing a chronic infection of slow progression, suggesting that the fungus has adapted to the human host [5].
Dermatophytosis is caused by Malassezia and Superficial candidiasis that are the most common types of superficial mycoses. On the other hand, tinea nigra, black and white piedra are the least common types that caused by non-dermatophytic molds. The estimated lifetime risk of acquiring dermatophytosis (tinea infection) is between 10 and 20 percent [6].
Dermatophytic infection increases during the summer and spring [7]. Socioeconomic factors, cultural factors, and climate conditions are not only responsible for the increased prevalence in the tropics but also influence the type of fungal infection in a particular geographic area [8]. Table 1 summarises the most prevalent dermatophytes that cause illness in people. The main problem with these infections is the recurrence.
Table 1: Dermatophytes causing disease in humans
|
Species |
Incidence |
Natural habitat |
Special features |
Associated condition |
|
Epidermophyton floccosum |
Common |
Humans |
Third most common organism |
Tinea cruris, pedis, manuum, and onychomycosis |
|
Microsporum audouinii |
Less common* |
Humans |
Ectothrix, Wood lamp green fluorescence |
Tinea capitis—more common in Europe |
|
Microsporum ferrugineum |
Common |
Humans |
- |
Tinea capitis |
|
Trichophyton rubrum |
Very common |
Humans |
Most common organism worldwide, 58% |
Tinea corporis, cruris, pedis, manuum, and onychomycosis and Majocchi granuloma |
|
Trichophyton tonsurans |
Common |
Humans |
Endothrix, 3% |
Tinea capitis—majority of cases in United States. Common cause of tinea corporis worldwide |
|
Trichophyton violaceum |
Less common |
Humans |
Endothrix |
Tinea capitis—endothrix |
|
Trichophyton mentagrophytes var interdigitale |
Common |
Humans |
Second most common organism causing tinea corporis and pedis, 27% |
Tinea corporis, cruris, pedis (interdigital), manuum, and onychomycosis |
Clinical Manifestations
The most essential clue to a correct diagnosis and therapy is the clinical presentation. Human dermatomycoses are most often caused by anthrophilic dermatophytes (which are commonly isolated from human infection). These elicit a restricted host response and are least likely to cause severe inflammation or resolve spontaneously [9]. Generally, severe inflammation is a component of dermatophytosis which is true in the case of tinea infections caused by zoophilic species.
Diagnosis
Diagnostic tests can confirm the clinical suspicion of dermatophytosis. Accurate diagnostic tests and correct etiological classification are indispensable. Treatment should not be started only on the basis of clinical symptoms, as other disease entities with fundamentally different pathogenesis may mimic the clinical appearance of contact dermatitis, thus requiring different therapeutic strategies. In most cases, a simple potassium hydroxide (KOH) preparation with mycologic examination under a light microscope can confirm the presence of dermatophytes. Occasionally, culture media (including indicator media) or histologic examination may be useful in making the diagnosis [10].
Evaluation of Histopathology
Biopsy specimens may be sent to a pathologist for examination if the diagnosis of a dermatophyte infection is still in doubt following office testing or treatment failure. The periodic acid–Schiff staining reveals fungal components. [11].
Treatment Considerations for Fungal Infections
For the treatment of fungal infections, a number of medicines are available, including topical and systemic treatments. Newer medicines are still being produced with success, bioavailability, fewer side effects, minimal recurrences, and ease of application. Antifungal washes/shampoos have been used for many years.
Dermatophytosis
Topical treatment is usually preferred for “localized” infections or those of limited spread and oral treatments for more extensive infections in the case of dermatophytosis affecting the skin.
Candida Infection of the Skin
Candida infections of the skin respond well to a range of antifungals available in cream, powder, or solution formulations [11, 12]. Useful antifungals for candidiasis are azole drugs (econazole, clotrimazole, ketoconazole, and miconazole).
Malassezia Infections
Pityriasis Versicolor - A wide range of different antifungal drugs are effective in pityriasis Versicolor [13], and cure rates of over 85% can be achieved. In pityriasis Versicolor, topically applied azole antifungals like miconazole, clotrimazole, ketoconazole, and sertaconazole work well.
Use of Ketoconazole Solution in Different Fungal Infections
Antimycotics in the imidazole family has a broad spectrum of activity against a variety of fungi and have been widely used as topical treatments for the treatment of superficial mycoses for years together. They act by inhibiting lanosterol 14α-demethylase which catalyzes lanosterol to ergosterol conversion (the primary sterol derivative of the fungal cell membrane) shown in figure 2, so this, in turn, results in membrane permeability changes incompatible with fungal growth and survival [14].
Figure 2: Ketoconazole inhibiting the synthesis of ergosterol (the main fungal sterol)
Research Studies on Ketoconazole
Efficacy Study
Many studies on use of ketoconazole solution has shown to be highly effective and well tolerated for the treatment of Pityriasis versicolor [15] and other fungal infections with significant reduction in eradication of the causative organism. In Tinea capitis, use of ketaconazole shampoo along with oral antifungal therapy has shown to decrease the carriage of viable spores responsible for the disease contagion and re-infection and may shorten the cure rate with oral antifungal [16]. In a study, the use of antifungal shampoo/solution along with oral antifungal has been shown to significantly improve the fungal infection in one month. 96% of the patients in the intervention group and 60% in the non-intervention group showed improvement and the difference between the 2 groups was statistically significant (P<0.001). The main challenge is the recurrence after completion of the therapy. After 3 months and 6 months of treatment, the rate of recurrence in the patients who received antifungal shampoo was 4%. But in the non-intervention group who did not receive the antifungal wash, the recurrence rate was 22% and 60% after 3 months and 6 months of treatment respectively. The study done, it reveals that in patients with fungal infections, if antifungal treatment is given along with a prophylactic course of antifungal wash/shampoo, the cure is faster and the recurrences are minimal (figure 3) [14].
Figure 3: Trend of recurrence of fungal infection among intervention and non-intervention group
Nizral 2% - Globally established anti-dandruff shampoo solution is a textbook brand with consistent quality since four decades. A potent antifungal effectively kills the fungus and ensures treatment with lower recurrence rates. Nizral 2% solution contains micronized ketoconazole which is manufactured by using micronized technology. This unique formulation/technology leads to better penetration and gets uniformly distributed in the affected dermis/epidermis resulting in greater degree of efficacy. It has anti-inflammatory and anti-proliferative properties. With its low viscosity, it allows easy spread ability on the affected area. Nizral 2% treats the root cause of many fungal infections and relieves redness and itching. 2% Ketoconazole is recommended by Danish Society of Dermatology for Pityriasis versicolor and Seborrheic Dermatitis. Adding Nizral wash to antifungal treatment ensures higher cure with lower recurrence rates.
Conclusion
Fungal infections remain a continuous and growing threat to human health. These infections have significant social, psychological, occupational, and health consequences that are all bad. Persistent infections can significantly reduce one's quality of life. Topical delivery of ketoconazole solution, perhaps the best route against major skin dermatophytes, ensures it has direct access to the target and has a greater retention rate. Topical delivery contributes to reduced systemic toxicity and avoids pre-systemic metabolism. Advantages of topical delivery further include site-specific drug delivery, reduced systemic toxicity, increased patient compliance, increased efficacy of treatment, and improved bioavailability. Antifungal therapy combined with antifungal wash prophylaxis dramatically reduced the recurring rate of fungal infections. As a result, preventive antifungal wash should be used while treating fungal infections in addition to oral and topical medication to improve treatment efficacy and minimize the risk of recurrence.
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