|Year : 2017 | Volume
| Issue : 3 | Page : 19-23
Systemic therapy of dermatophytosis: Practical and systematic approach
Madhu Rengasamy1, Janaki Chellam2, Sentamilselvi Ganapati2
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 Publication||10-Oct-2017|
Ganesh Flats, New No 15, School Road, Perambur, Chennai - 600 011, Tamil Nadu
Source of Support: None, Conflict of Interest: None
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 2020 Feb 22];1, Suppl S1:19-23. Available from: http://www.cdriadvlkn.org/text.asp?2017/1/3/19/216276
| Introduction|| |
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. 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. 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. Infection that recurs within few weeks after completion of therapy is termed as “recurrent dermatophytosis.” 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|| |
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., Systemic AFAs such as griseofulvin, terbinafine, ketoconazole, fluconazole, and itraconazole have been known to be active against dermatophytes, terbinafine being the only fungicidal drug.,, 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].,,,,, 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. 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.
| Practical and Systematic Approach|| |
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|| |
- 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,
- 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.
| Treatment Options|| |
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. 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.,,, 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.
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.
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].,,
|Table 5: Literature-based treatment options for chronic, widespread dermatophytosis|
Click here to view
- 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|| |
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., Tamura et al. observed that the combination of amorolfine and itraconazole had synergistic or additive effects.
| Points to Remember|| |
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|| |
- 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:,
- Warfarin, sulfonylureas
- Ritonavir, indinavir, saquinavir
- Cyclosporine, tacrolimus, sirolimus
- Verapamil, digoxin
- Dexamethasone, methylprednisolone, budesonide.
| Drug Interactions of Terbinafine|| |
- Increased levels caused by fluconazole and cyclosporine
- Decreased levels of terbinafine caused by rifampicin
- Terbinafine increases the levels of the following co-administered drugs:,
- Tricyclic antidepressants – doxepin, amitriptyline
- Antiarrhythmics – Class 1c flecainide and propafenone
| Conclusion|| |
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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Conflicts of interest
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| References|| |
Dogra S, Uprety S. The menace of chronic and recurrent dermatophytosis in India: Is the problem deeper than we perceive? Indian Dermatol Online J 2016;7:73-6.
] [Full text]
Sentamilselvi G, Kamalam A, Ajithadas K, Janaki C, Thambiah AS. Scenario of chronic dermatophytosis: An Indian study. Mycopathologia 1997-1998;140:129-35.
Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin 2003;21:395-400, v.
Ellis D, Watson A. Systemic antifungal agents for cutaneous fungal infections. Aust Prescr 1996;19:72-5.
Korting HC, Schöllmann C. The significance of itraconazole for treatment of fungal infections of skin, nails and mucous membranes. J Dtsch Dermatol Ges 2009;7:11-9, 11-20.
Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silny W. A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidosis. Int J Dermatol 1998;37:703-5.
Hay RJ, Ashbee HR. Fungal infections. In: Griffiths CE, Barker J, Bleiker T, Chalmers R, Creamer D, editors. Rook's Textbook of Dermatology. 9th
ed, Vol. 2. West Sussex: Wiley Blackwell; 2016. p. 923-1018.
Schieke SM, Garg A. Superficial fungal infection. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine. 8th
ed, Vol. 2. New York: The McGraw-Hill Companies; 2012. p. 2277-97.
Manjunath Shenoy M, Suchitra Shenoy M. Superficial fungal infections. In: Sacchidanand S, Oberoi C, Inamdar AC, editors. IADVL Textbook of Dermatology. 4th
ed., Vol. 1. Mumbai: Bhalani Publishing House; 2015. p. 459-516.
Gupta AK. Systemic antifungal agents. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd
ed. China: Elsevier Saunders; 2013. p. 98-120.
Elewski BE, Hughey LC, Sobera JO, Hay R. Fungal diseases. In: Bolognia JL, Jorizzo JL, Schaffer JV, editors. Dermatology. 3rd
ed, Vol. 2. China: Elsevier Saunders; 2012. p. 1267.
Sentamilselvi G. Dermatophytosis. In: Sentamilselvi G, Janaki VR, Janaki C, editors. The Handbook of Dermatomycology & Colour Atlas. 1st
ed. India: Sentamilselvi; 2006. p. 9-15.
Majid I, Sheikh G, Kanth F, Hakak R. Relapse after oral terbinafine therapy in dermatophytosis: A clinical and mycological study. Indian J Dermatol 2016;61:529-33.
] [Full text]
Ely JW, Rosenfeld S, Seabury Stone M. Diagnosis and management of tinea infections. Am Fam Physician 2014;90:702-10.
Amichai B, Grunwald MH, Davidovici B, Shemer A. Sunlight is said to be the best of disinfectants: The efficacy of sun exposure for reducing fungal contamination in used clothes. Isr Med Assoc J 2014;16:431-3.
Miskeen AK, Uppulri P. Dermatophytosis. In: Tahiliani S, editor. Mycoscope. New Delhi: IJCP Publications Ltd.; 2016. p. 29-33.
Agarwal RK, Gupta S, Mittal G, Khan F, Roy S, Agarwal A. Antifungal susceptibility testing of dermatophytes by agar based disk diffusion method. Int J Curr Microbiol Appl Sci 2015;4:430-6.
Bhatia VK, Sharma PC. Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method. Indian J Med Microbiol 2015;33:533-7.
] [Full text]
Sabtharishi V, Katragadda R, Ravinder T. A study on the antifungal susceptibility pattern of dermatophytes isolated in a tertiary care hospital. Int J Bioassays 2017;6:5379-82.
Dabas Y, Xess I, Singh G, Pandey M, Meena S. Molecular identification and antifungal susceptibility patterns of clinical dermatophytes following CLSI and EUCAST guidelines. J Fungi 2017;3:1-10. Available from: http://www.mdpi.com
. [Last accessed on 2017 May 03].
Kanafani ZA, Perfect JR. Resistance to antifungal agents: Mechanisms and clinical impact. Clin Infect Dis 2008;46:120-8.
Thursky KA, Playford EG, Seymour JF, Sorrell TC, Ellis DH, Guy SD, et al.
Recommendations for the treatment of established fungal infections. Intern Med J 2008;38:496-520.
Jerajani H, Janaki C, Kumar S, Phiske M. Comparative assessment of the efficacy and safety of sertaconazole (2%) cream versus terbinafine cream (1%) versus luliconazole (1%) cream in patients with dermatophytoses: A pilot study. Indian J Dermatol 2013;58:34-8.
] [Full text]
Moodahadu-Bangera LS, Martis J, Mittal R, Krishnankutty B, Kumar N, Bellary S, et al.
Eberconazole – Pharmacological and clinical review. Indian J Dermatol Venereol Leprol 2012;78:217-22.
] [Full text]
Tamura T, Asahara M, Yamamoto M, Yamaura M, Matsumura M, Goto K, et al
. In vitro
susceptibility of dermatomycoses agents to six antifungal drugs and evaluation by fractional inhibitory concentration index of combined effects of amorolfine and itraconazole in dermatophytes. Microbiol Immunol 2014;58:1-8.
Gubbins PO, Heldenbrand S. Clinically relevant drug interactions of current antifungal agents. Mycoses 2010;53:95-113.
Brüggemann RJ, Alffenaar JW, Blijlevens NM, Billaud EM, Kosterink JG, Verweij PE, et al.
Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 2009;48:1441-58.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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