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Year : 2017  |  Volume : 1  |  Issue : 3  |  Page : 19-23

Systemic therapy of dermatophytosis: Practical and systematic approach

1 Chairperson, IADVL Task-force Against Recalcitrant Tinea (ITART); Department of Dermatology (Mycology), Madras Medical College, Chennai, Tamil Nadu, India
2 Senior Consultant Dermatologist, Chennai, Tamil Nadu, India

Date of Web Publication10-Oct-2017

Correspondence Address:
Madhu Rengasamy
Ganesh Flats, New No 15, School Road, Perambur, Chennai - 600 011, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CDR.CDR_36_17

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Superficial dermatophytosis caused by dermatophytes belonging to the three genera, “Trichophyton, Microsporum and Epidermophyton” is the most common fungal infection seen in human beings, worldwide. Medical fraternity in India has been observing an increase in the prevalence of dermatophytosis and that too of the difficult to treat recalcitrant, recurrent and chronic dermatophytosis, over the last 3-4 years. This change in the clinical scenario with increasing frequency of treatment failures has given rise to innumerable treatment options mainly based on individual's experience, as the therapeutic regimens given in the standard textbooks, both Western and Indian, have ceased to result in a good clinical response. With this background, this article will focus on the treatment schedule given in standard textbooks and the current modifications that have evolved to treat dermatophytosis of the glabrous skin.

Keywords: Antifungal drugs, dermatophytosis, glabrous skin

How to cite this article:
Rengasamy M, Chellam J, Ganapati S. Systemic therapy of dermatophytosis: Practical and systematic approach. Clin Dermatol Rev 2017;1, Suppl S1:19-23

How to cite this URL:
Rengasamy M, Chellam J, Ganapati S. Systemic therapy of dermatophytosis: Practical and systematic approach. Clin Dermatol Rev [serial online] 2017 [cited 2023 Jan 29];1, Suppl S1:19-23. Available from: https://www.cdriadvlkn.org/text.asp?2017/1/3/19/216276

  Introduction Top

Dermatophytosis, the most common superficial fungal infection caused by keratinophilic fungi, has been on the rise in India over the last 3-4 years, with an increase in the occurrence of difficult-to-treat recalcitrant, recurrent, and chronic dermatophytosis.[1] While multiple factors such as global warming, migration of laborers, increased frequency of wearing tight and synthetic clothing, obesity, sedentary lifestyle, increasing prevalence of Trichophyton mentagrophytes and poor compliance of patients are considered to be the reasons for this havoc, one of the most important factors is the commonly prevalent, rampant abuse of topical steroid antifungal combination creams by the patients, who mostly purchase them over the counter (OTC) or at times as prescribed by practitioners. Dermatophytosis which was once considered as an easy infection to treat has now evolved into a difficult-to-treat menace across the country. Before moving on to the systemic treatment, let us consider the following terminologies that are relevant in the current scenario: “chronic dermatophytosis” refers to the presence of infection for 1 year with several relapses or for a total duration of >1 year in spite of treatment.[2] However in the current scenario, a patient is said to have chronic dermatophytosis, when the infection lasts for more than 6 months to 1 year in spite of regular treatment.[1] Infection that recurs within few weeks after completion of therapy is termed as “recurrent dermatophytosis.”[1] The term, “recalcitrant dermatophytosis” is used when there is no clinical cure in spite of treatment with systemic antifungal agents (AFAs) in an appropriate dose and duration.

  Systemic Therapy Top

Standard recommendations for systemic therapy of dermatophytosis are the presence of multiple site involvement, extensive tinea corporis, recurrent or chronic dermatophytosis, tinea pedis, tinea capitis, tinea unguium, localized infection unresponsive to topical AFAs, and immunocompromised states.[3],[4] Systemic AFAs such as griseofulvin, terbinafine, ketoconazole, fluconazole, and itraconazole have been known to be active against dermatophytes, terbinafine being the only fungicidal drug.[4],[5],[6] Among these drugs, itraconazole and terbinafine are more often prescribed compared to griseofulvin and fluconazole, probably because the latter require longer duration of treatment. Various therapeutic options for the treatment of tinea corporis/ tinea cruris and tinea pedis mentioned in the standard textbooks currently followed are summarized in [Table 1] and [Table 2].[7],[8],[9],[10],[11],[12] Most of these treatment options, however, have been found to be noneffective in the therapy of the recurrent, recalcitrant, and chronic widespread dermatophytosis and steroid-modified tinea that is currently prevalent across the country. Duration of treatment mentioned in the Western literature is not applicable to treat dermatophytosis in a tropical country like India, which is facing hotter and prolonged summers and scant rainfall in the recent past, due to global warming. A study by Majid et al. done at Srinagar concluded that incomplete cure was very common after a 2-week course of terbinafine 250 mg.[13] The need of the hour is therapeutic studies to evolve national guidelines for the management of dermatophytosis in the Indian population, as the treatment of dermatophytosis in the current scenario is mostly experience based than evidence based.
Table 1: Current therapeutic regimens for tinea corporis/tinea cruris

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Table 2: Current therapeutic regimens for tinea pedis

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  Practical and Systematic Approach Top

The current scenario of increasing treatment failures necessitates a systematic approach in the patients with dermatophytosis. Lack of evidence-based studies has resulted in innumerable therapeutic regimens based on individual experience. For convenience of treatment strategy, authors opine that patients with dermatophytosis may be categorized into the following four groups:

  • Group 1a: Patients with the first episode, with no prior history of topical or systemic treatment – this group forms a very small proportion due to the rampant practice of application of topical steroid antifungal (TSAF) combination creams.
  • Group 1b: Patients with the first episode, with a prior history of application of TSAF combination creams or irregular systemic treatment
  • Group 2: Patients who have been on irregular treatment with multiple antifungal drugs given for a suboptimal duration or patients with recurrent episodes within a period of 6 months
  • Group 3: Patients with chronic dermatophytosis (several relapses for >6 months to 1 year) or recalcitrant dermatophytosis in spite of regular treatment.

  General Principles of Treatment Top

  • Duration of the treatment is always individualized depending on the clinical response and hence drugs should be continued until clinical cure
  • Strict avoidance of OTC drugs/prescribed topical steroid antifungal combination creams[3],[14]
  • Attention to the drug–drug interactions, especially in patients on multiple drugs
  • Antihistamines to alleviate pruritus
  • Counseling during the first visit to ensure proper adherence to the general measures [Table 3] which are very important to get rid of the infection. Dermatologist's time invested during the first visit for counseling is directly proportional to the success of the clinical outcome.
Table 3: General measures

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  Treatment Options Top

Group 1a: Patients with the first episode, with no prior history of treatment

  • These patients may be started on one of the drugs mentioned in [Table 4] and advised to come for a review at the end of 2-3 weeks if there is no regression in symptoms or at 4 weeks if there is clinical improvement. Usually, this group of patients respond well to treatment
  • But yet, on review, if there is only a partial response with some active lesions and itching, one has to assess the predisposing factors and then up dose the drug as follows:
  • Tablet griseofulvin 500 mg twice a day, tablet fluconazole 150 mg thrice weekly, tab terbinafine 500 mg once a day, and tablet itraconazole 100 mg twice a day
  • On the next review at the end of 2–3 weeks, if there is no response along with occurrence of new lesions, we should consider changing the drug.
  • Antifungal resistance is considered to be one of the reasons for the prevailing menace of chronic and recurrent dermatophytosis in India. Although there are isolated reports of true resistance, experts opine that the term “resistance” is best avoided at present, as definite breakpoints for dermatophytes are yet to be determined by the Clinical Laboratory Standard Institute, USA.[16] Antifungal susceptibility tests for dermatophytes done across the country have revealed an increase in the minimum inhibitory concentration (MIC) values for fluconazole, terbinafine, and griseofulvin.[17],[18],[19],[20] Adequate or higher dosage of the drug would help to combat the increase in MIC values. It has also been observed that MIC values do not always directly associate with response to antifungal therapy.[21]
Table 4: First episode treatment option

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Group 1b: Patients with the first episode, with a prior history of TSAF cream application or irregular systemic treatment for a suboptimal duration

This group of patients may be managed as in Group 1a, but require a longer duration of treatment to cure steroid-modified tinea. Suboptimal duration of treatment breeds clinical failure.[21]

Group 2: Patients with irregular treatment/recurrent episodes within 6 months

  • After proper history taking with regard to the medications, they may be started on an AFA that has not been given earlier or in the recent past
  • Review at the end of 2–3 weeks:
    • Partial response/few active lesions –
    • Up dosing No response/new lesions – Change drug.
  • Review 2 weeks after up dosing:
    • Good response – continue the same
    • In case of partial response – add another AFA of different class.

Group 3: Patients with chronic dermatophytosis or recalcitrant dermatophytosis

David Ellis and Alan Watson (1996), Sentamilsevi (2003), and Thursky et al. (2008) have recommended treatment options for chronic and/or widespread nonresponsive tinea as summarized in [Table 5].[4],[12],[22]
Table 5: Literature-based treatment options for chronic, widespread dermatophytosis

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  • These patients, when on a single drug, could be either continued on regular dosage for a longer duration (3–6 months depending on the drug given) if there is clinical response or given double the dose for conventional duration or longer until clinical cure
  • If there is no response at the end of 3 weeks, combination therapy has to be planned. Various combinations of systemic antifungals that are in vogue for treating chronic or recalcitrant dermatophytosis are as follows:

    • Fluconazole/itraconazole + terbinafine
    • Griseofulvin + terbinafine
    • Griseofulvin + fluconazole/itraconazole.

  • It is mandatory to perform a baseline complete hemogram and liver and renal function tests, whenever up dosing or combination therapy is contemplated and subsequently periodic monitoring has to be done. Baseline serum electrolytes and cardiac evaluation have to be done, when itraconazole is planned for a long duration.

  Combination of Systemic Antifungal Agent With Topical Antifungal Agent Top

Topical AFAs provide high concentration of the drug at the site of action and hence are preferred to be used along with the systemic antifungal drugs. Different classes of topical and systemic AFAs may be combined. Among the azoles, eberconazole and sertaconazole have the advantage of anti-inflammatory activity.[23],[24] Tamura et al. observed that the combination of amorolfine and itraconazole had synergistic or additive effects.[25]

  Points to Remember Top

Proper instructions with regard to the consumption of griseofulvin and itraconazole are important to ensure therapeutic efficacy. Griseofulvin tablet has to be consumed after a fatty meal. Capsule or tablet itraconazole should be swallowed immediately after full meals. Elaborate history of the other medications is very important, as drug–drug interactions may affect the therapeutic outcome.

  Drug Interactions of Itraconazole Top

  • Itraconazole is contraindicated in patients with ventricular dysfunction/cardiac failure and in patients who are on lovastatin or simvastatin
  • Itraconazole and cyclosporine together enhances renal toxicity
  • Itraconazole and statins – rhabdomyolysis
  • Itraconazole and nifedipine – pedal edema
  • Decreased levels of itraconazole caused by antacids, H2 receptor antagonists, proton pump inhibitors, didanosine, rifampicin, phenytoin, phenobarbitone, carbamazepine, isoniazid, and nevirapine
  • Increased levels of itraconazole caused by erythromycin, clarithromycin, ciprofloxacin, indinavir, and ritonavir
  • Itraconazole increases the levels of the following co-administered drugs:[26],[27]

    • Warfarin, sulfonylureas
    • Ritonavir, indinavir, saquinavir
    • Cyclosporine, tacrolimus, sirolimus
    • Atorvastatin
    • Verapamil, digoxin
    • Dexamethasone, methylprednisolone, budesonide.

  Drug Interactions of Terbinafine Top

  • Increased levels caused by fluconazole and cyclosporine
  • Decreased levels of terbinafine caused by rifampicin
  • Terbinafine increases the levels of the following co-administered drugs:[26],[27]

    • Tricyclic antidepressants – doxepin, amitriptyline
    • Beta-blockers
    • Antiarrhythmics – Class 1c flecainide and propafenone
    • Anticoagulants.[26],[27]

  Conclusion Top

Superficial dermatophytosis is no longer a simple, cutaneous fungal infection that is easily amenable to treatment. It has evolved into a chronic and recurrent, difficult-to-treat infection which affects the physical and the social well-being of the affected patients. While there could be multiple reasons for this change in the trend of dermatophytosis, one of the most important factors that needs immediate attention in a war footing is the abuse of the OTC topical steroid antifungal creams. We need to create health awareness about dermatophytosis and the topical steroid abuse among the practitioners, pharmacists, and the public by means of meetings, social media mass campaign, posters, and pamphlets. With regard to the treatment of dermatophytosis, counseling is indeed the cornerstone of therapy. Systemic treatment provided in a systematic manner, based on the clinical response seen in patients, will definitely yield a good therapeutic outcome. Duration of treatment is best individualized, with clinical cure considered as the end point.

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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