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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 3  |  Page : 38-41

Management of dermatophytosis in elderly and with systemic comorbidities


Department of Dermatology, Venereology and Leprosy, ESIC Medical College and PGIMSR, Bengaluru, Karnataka, India

Date of Web Publication10-Oct-2017

Correspondence Address:
Ragunatha Shivanna
Department of Dermatology, Venereology and Leprosy, ESIC Medical College and PGIMSR, Rajaji Nagar, Bengaluru - 560 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_32_17

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  Abstract 


Various factors unique to elderly patients such as physical, physiological, psychological, and socioeconomic factors affect the outcome of dermatophytic infection and its management. The associated comorbidities such as renal and hepatic failure and polypharmacy influence the pharmacological properties of antifungal agents. These drugs are potent inhibitors of hepatic enzymes involved in drug metabolism leading to accumulation and subsequent toxicity of various classes of drugs. All these factors are considered in the management of dermatophytosis in elderly especially with comorbidities.

Keywords: Antifungal therapy, dermatophytosis, elderly


How to cite this article:
Shivanna R, Rajesh. Management of dermatophytosis in elderly and with systemic comorbidities. Clin Dermatol Rev 2017;1, Suppl S1:38-41

How to cite this URL:
Shivanna R, Rajesh. Management of dermatophytosis in elderly and with systemic comorbidities. Clin Dermatol Rev [serial online] 2017 [cited 2019 Jan 24];1, Suppl S1:38-41. Available from: http://www.cdriadvlkn.org/text.asp?2017/1/3/38/216272




  Introduction Top


The management of dermatophytosis has become a big concern owing to various factors related to host, causative agent, and environment. Antifungal therapy in elderly and in those with systemic comorbidities is very challenging because of restricted therapeutic options available for dermatologists. Literature on the management of dermatophytosis in elderly is limited. In general, pharmacotherapy in elderly patients is limited by physical, physiological, psychological, and socioeconomic factors. The presence of comorbid diseases and associated polypharmacy predispose them to recurrent fungal infections and significant drug interactions. Similar challenges are encountered in patients with renal or hepatic dysfunction. A thorough knowledge of pharmacokinetic and pharmacodynamic characteristics of antifungal agents and associated potential drug interactions is essential for successful management of dermatophytosis in such clinical scenarios.


  Epidemiology Top


Old-age, comorbid diseases including renal and hepatic disorders with inherent immunological alteration and their treatment influence the manifestation of dermatophytic infection.

In elderly

Dermatophytosis including onychomycosis constitutes about 16% of total cutaneous diseases in elderly patients attending dermatology clinic,[1] and up to 23% in the elderly diabetic.[2] Among dermatophytoses, tinea pedis, and onychomycosis are more common in elderly, especially in males.[3] Onychomycosis has been diagnosed in nearly half of patients presenting with abnormal nails. Distal and lateral subungual are the most common types and Trichophyton rubrum and mentagrophyte, the common causative organisms.[4],[5] The prevalence of onychomycosis increases with age, with more than 20% occurrence in those above 60 years of age.[6]

In renal failure

The drug-induced immunosuppression in renal transplant patients put them at increased risk of dermatophytic infections, compared to other renal disorders. Dermatophytosis has been reported in 42% renal transplant patients, with tinea cruris and corporis being the common clinical types. The lesions tend to be noninflammatory, scaly and without central clearing, and spread rapidly and extensively following renal transplant.[7] Deeper dermal dermatophytosis presenting as papules, nodules, abscesses, and erythematous plaque has been reported in these patients.[8] Patients with chronic kidney disease are also susceptible to dermatophytic infections especially onychomycosis. In patients on hemodialysis, onychomycosis is the second most common disease involving nails. In patients of end-stage renal disease (ESRD), dermatophtytosis is common in those with underlying diabetes than other conditions. The risk of dermatophytosis is not associated with duration of the evolution of ESRD or hemodialysis. There has been no difference between patients with ESRD and those with normal renal function in relation to organisms isolated and their susceptibility to azoles and terbinafine.[9]

In hepatic failure

Extensive deep dermatophytosis involving hair follicles and dermis caused by T. rubrum has been reported in patients with liver cirrhosis. These patients presented with dermal nodules and purpuric rashes to hemorrhagic nodules.[10] Onychomycosis has been reported as the most common nail changes that occur in patients with hepatic failure constituting 18% of cases.[11]


  Determinants of Treatment of Dermatophytosis in Elderly Top


Various factors unique to old age such as physiological changes, comorbidities including renal and hepatic failure, polypharmacy, and limitations in personal care need to be considered before choosing appropriate therapy. The extent and site of infection also need to be considered.

Type and extent of infection

As in other age-groups, extensive disease and the involvement of palms, soles, and nails requires treatment with systemic antifungal agents. Even in limited involvement, the presence of comorbidities is an indication for systemic drugs.

Physiological changes

The secretary function of sebaceous and sweat glands decrease with age, leading to dry skin, which may be the reason for less prevalence of extensive dermatophytosis in elderly. The glomerular filtration rate decreases naturally at the rate of approximately 1 ml/min/year after the age of 30 years as a part of senescence. It is an important factor to be considered while prescribing drugs with predominantly renal excretion.[12]

Comorbidities

Elderly individuals commonly suffer from multiple diseases affecting various organ systems. This can lead to immunosuppression predisposing them to cutaneous and systemic infections. Elderly diabetics have 2–3-folds increased risk of onychomycosis compared to nondiabetics.[13]

Drug interactions

Comorbidities in elderly lead to polypharmacy which is associated with significant clinically relevant drug interactions with antifungal agents [Table 1].[14],[15],[16] This can be due to either pharmacodynamic or pharmacokinetic alterations, the former results from the effect of both drugs on the same physiological process and the latter is commonly mediated by inhibition or induction of hepatic cytochrome enzyme system, which is difficult to predict due to individual variability in response.
Table 1: Common and clinically significant drug interactions of azole group of antifungal agents

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The effects of drugs on hepatic enzyme system are obvious only when given orally because the drugs have to enter liver during the first pass before entering the systemic circulation. Azoles compete for the cytochrome P-450 (CYP) enzyme, a principle drug metabolizing enzyme in humans, and decrease the elimination of drugs that are metabolized by this enzyme system. The subsequent elevated blood levels of drugs increase the pharmacological effects and dose-dependent toxicity. Ketoconazole is found to be the strongest inhibitor of CYP3A4. Itraconazole is potent and fluconazole is the weakest inhibitor among all azoles. However, fluconazole inhibits the enzyme in higher doses. The azoles interact with myriad group of drugs. Hence, proper precaution and careful monitoring of drug levels and toxicity are important when the clinical situation necessitates the concomitant use of azoles (especially ketoconazole and itraconazole) and drugs metabolized by CYP3A4. Terbinafine has no significant drug-drug interaction.[14]

Limitations in personal care

The elderly patients are usually dependent on caretakers for personal care because of musculoskeletal ailments and age-related forgetfulness. Hence, complex antifungal therapy with topical agents can affect the compliance and may not be feasible in the majority of patients.


  Management Strategy Top


In elderly

A shorter duration of therapy with efficient antifungal agents is ideal. Terbinafine with clinically insignificant drug interactions seems more rational than azoles in an elderly patient taking multiple drugs for various comorbid diseases.[15] Itraconazole is better avoided in patients on other drugs metabolized by CYP-450 3A enzyme system. The choice of drug, route of administration, dosage and duration of treatment is same as in antifungal therapy in other age groups. However, there are certain factors in elderly which indicate poor response to therapy or increased rate of recurrence [Table 2].[6] Griseofulvin is not recommended because of low cure rates, high relapse rate, and prolonged daily dosage regimen, especially in onychomycosis.[15]
Table 2: Indicators of poor response of onychomycosis to therapy/recurrences in elderly

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In renal failure

The determinants of treatment include comorbidities, polypharmacy, and type and extent of dermatophytic infection. The degree of renal insufficiency, causative organisms, and pharmacokinetic properties of antifungal agents need consideration. Only fluconazole and flucytosine are excreted renally as unchanged drug or active metabolites. Terbinafine is excreted primarily through renal systems. In patients with decreased creatinine clearance, fluconazole, and terbinafine require dose adjustment. The terminal half-life of terbinafine and fluconazole increase in patients with renal impairment. Hence, in patients with creatinine clearance <50 ml/min their doses are to be halved.[9],[15]

In hepatic failure

It is also associated with defective host immune response, comorbidities, and polypharmacy. In general, liver diseases that affect hepatic blood flow, protein binding, and enzyme activity significantly alter drug pharmacokinetics. All except cirrhosis cause only mild alterations in hepatic drug clearance.[17] Itraconazole, ketoconazole, and terbinafine are known to cause acute liver failure. The relative risk (RR) of causing acute liver injury being highest with ketoconazole (RR-228), followed by itraconazole (RR-17.7) and terbinafine (RR-4.2).[15] Hence, these drugs should be avoided in patients with hepatic impairment.[15],[18] Griseofulvin is not indicated in patients with hepatic failure.[15] Concomitant alcohol intake, elderly patients, drugs with significant hepatic metabolism and daily dosage of drug exceeding 50 mg are the risk factors for drug-induced hepatotoxicity.[18],[19]


  Conclusion Top


The dermatophytosis in elderly and in patients with renal or hepatic impairment can be managed successfully by choosing an appropriate antifungal agent based on patient characteristics, pharmacokinetic, and pharmacodynamics properties, and potential drug interactions. Clinical monitoring of drug toxicity and drug levels is important during antifungal therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jindal R, Jain A, Roy S, Rawat SD, Bhardwaj N. Skin Dis orders Among Geriatric Population at a Tertiary Care Center in Uttarakhand. J Clin Diagn Res 2016;10:WC06-8.  Back to cited text no. 1
    
2.
Asokan N, Binesh VG. Cutaneous problems in elderly diabetics: A population-based comparative cross-sectional survey. Indian J Dermatol Venereol Leprol 2017;83:205-11.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Yalçin B, Tamer E, Toy GG, Oztaş P, Hayran M, Alli N, et al. The prevalence of skin diseases in the elderly: Analysis of 4099 geriatric patients. Int J Dermatol 2006;45:672-6.  Back to cited text no. 3
    
4.
Weinberg JM, Scheinfeld NS. Cutaneous infections in the elderly: Diagnosis and management. Dermatol Ther 2003;16:195-205.  Back to cited text no. 4
    
5.
Loo DS. Cutaneous fungal infections in elderly. Dermatol Clin 2004;22:33-50.  Back to cited text no. 5
    
6.
Loo DS. Onychomycosis in the elderly: Drug treatment options. Drugs Aging 2007;24:293-302.  Back to cited text no. 6
    
7.
Sentamil Selvi G, Kamalam A, Ajithados K, Janaki C, Thambiah AS. Clinical and mycological features of dermatophytosis in renal transplant recipients. Mycoses 1999;42:75-8.  Back to cited text no. 7
    
8.
Rouzaud C, Hay R, Chosidow O, Dupin N, Puel A, Lortholary O, et al. Severe dermatophytosis and acquired or innate immunodeficiency: A review. J Fungi 2016;2:4. Available from: http://www.mdpi.com/2309--608X/2/1/4. [Last accessed on 2017 May 12].  Back to cited text no. 8
    
9.
Irimie M, Tătaru A, Oantă A, Moga M.In vitro susceptibility of dermatophytes isolated from patients with end-stage renal disease: A case-control study. Mycoses 2014;57:129-34.  Back to cited text no. 9
    
10.
Wu LC, Sun PL, Chang YT. Extensive deep dermatophytosis cause by Trichophyton rubrum in a patient with liver cirrhosis and chronic renal failure. Mycopathologia 2013;176:457-62.  Back to cited text no. 10
    
11.
Salem A, Gamil H, Hamed M, Galal S. Nail changes in patients with liver disease. J Eur Acad Dermatol Venereol 2010;24:649-54.  Back to cited text no. 11
    
12.
Glassock RJ, Winearls C. Ageing and the glomerular filtration rate: Truths and consequences. Trans Am Clin Climatol Assoc 2009;120:419-28.  Back to cited text no. 12
    
13.
Tan JS, Joseph WS. Common fungal infections of the feet in patients with diabetes mellitus. Drugs Aging 2004;21:101-12.  Back to cited text no. 13
    
14.
Albengres E, Le Louët H, Tillement JP. Systemic antifungal agents. drug interactions of clinical significance. Drug Saf 1998;18:83-97.  Back to cited text no. 14
    
15.
Elewski B, Tavakkol A. Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: A proven reality. Ther Clin Risk Manag 2005;1:299-306.  Back to cited text no. 15
    
16.
Gupta AK. Systemic antifungal agents. In: Wolverton SE, editor. Comprehensive Dermatologic Drug Therapy. 3rd ed. Edinburg: Saunders: 2013. p. 98-120.  Back to cited text no. 16
    
17.
Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol 2008;64:1147-61.  Back to cited text no. 17
    
18.
Suzuki A, Andrade RJ, Bjornsson E, Lucena MI, Lee WM, Yuen NA, et al. Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in vigiBase: Unified list based on international collaborative work. Drug Saf 2010;33:503-22.  Back to cited text no. 18
    
19.
Björnsson E. Review article: Drug-induced liver injury in clinical practice. Aliment Pharmacol Ther 2010;32:3-13.  Back to cited text no. 19
    



 
 
    Tables

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Abstract
Introduction
Epidemiology
Determinants of ...
Management Strategy
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