|Year : 2019 | Volume
| Issue : 2 | Page : 214-224
South Asian Epidemic of Antifungal Therapeutic Failures: Congress Proceedings and Take-home Messages. First International Congress of SAARCUM: South Asian Alliance against Recalcitrant Cutaneous Mycosis. 17 November 2018, Medanta – The Medicity, Gurugram, India
Parul Aggarwal1, Mahima Agrawal2, Sidharth Sonthalia3, Dharmendra Arora4, Poonam Sharma5
1 Department of Dermatology, SKINALIVE, Gurugram, Haryana, India
2 Department of Dermatology and STD, Lady Hardinge Medical College and SK Hospital, New Delhi, India
3 Department of Dermatology and Dermatosurgery, SKINNOCENCE: The Skin Clinic and Research Centre, Gurugram, Haryana, India
4 Department of Development Communication, Jamia Millia Islamia, New Delhi, India
5 Department of Dermatology and STD, Skin Institute and School of Dermatology (SISD), New Delhi, India
|Date of Web Publication||15-Mar-2019|
SKINNOCENCE: The Skin Clinic and Research Centre, C.2246, Sushant Lok.1, Block.C, Gurugram - 122 009, Haryana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Aggarwal P, Agrawal M, Sonthalia S, Arora D, Sharma P. South Asian Epidemic of Antifungal Therapeutic Failures: Congress Proceedings and Take-home Messages. First International Congress of SAARCUM: South Asian Alliance against Recalcitrant Cutaneous Mycosis. 17 November 2018, Medanta – The Medicity, Gurugram, India. Indian Dermatol Online J 2019;10:214-24
|How to cite this URL:|
Aggarwal P, Agrawal M, Sonthalia S, Arora D, Sharma P. South Asian Epidemic of Antifungal Therapeutic Failures: Congress Proceedings and Take-home Messages. First International Congress of SAARCUM: South Asian Alliance against Recalcitrant Cutaneous Mycosis. 17 November 2018, Medanta – The Medicity, Gurugram, India. Indian Dermatol Online J [serial online] 2019 [cited 2020 Feb 22];10:214-24. Available from: http://www.idoj.in/text.asp?2019/10/2/214/254302
The nuisance of widespread failure of antifungal pharmacotherapy in the treatment of superficial cutaneous mycosis, especially dermatophytic infections has become daunting for practitioners across South Asia. Although multiple sporadic attempts at the regional/national level have been conducted to find a solution to this menace in India, the need of the hour was the formation of a dedicated international alliance that eventuated in the creation of the South Asian Alliance against Recalcitrant CUtaneous Mycosis (SAARCUM), coordinated by Dr Sidharth Sonthalia (Dermatologist) from India, and involving participation from South Asian countries including Nepal, Sri Lanka, Bangladesh, Thailand, and Singapore. The second essential aspect of such an alliance i.e. involvement of medical specialists other than dermatology was also ensured. Today, SAARCUM is a conglomeration of dermatologists, microbiologists, epidemiologists, senior scientists involved in mycology research, internists, pediatricians, and psychiatrists.
DERMASOURCE INDIA (DSI), a well-known venture of dermatologists and management experts, credited with holding the first ever National Dermoscopy Conclave of India in 2015 followed by focused conclaves on niche areas like polycystic ovary syndrome (PCOS), platelet-rich plasma (PRP), psychodermatology, hair transplantation amongst others, and International Organizing partner for various Congresses held by different National Dermatology Associations/Societies (Nepal, University of Cairo, Spring Continental Congress of Dermatology, Tehran, and Sri Lankan College of Dermatologists – SLCD) organized the First International Congress of SAARCUM on 17th November, 2018 at Medanta – The Medicity, Gurugram, India [www.dermasourceindia.com].
The current DSI venture –First International Congress of SAARCUM – was governed by multi-regional and multi-specialty approach, the bare essentials to tackle the epidemic of antifungal therapeutic failures (AFTF) overwhelming South Asia and spreading across the globe. The scientific programme was delivered by including Chairpersons, 35 Speakers [Figure 1], 2 quiz masters, and presenters of 6 shortlisted Award papers and 5 E-Posters. International faculties included representatives from the National Societies of Dermatology of Nepal, Sri Lanka, and Bangladesh. Experienced faculties from different specialties contributed to multiple facets of clinical mycology.
The conference was attended by 162 delegates from across the length and breadth of India, and neighboring countries including Nepal, Bhutan, Bangladesh, and Sri Lanka. While the majority of delegates were dermatologists, a substantial number hailed from internal medicine and pediatrics, a positive trend since inclusion of all primary stake-holders is imperative to win this battle against mycoses.
The scientific proceedings started with the Award Paper session. Out of 17 abstracts received, the 6 most meritorious papers pertaining to research in cutaneous mycology were presented by the residents [Figure 2]. The DSI-SAARCUM inter-collegiate postgraduate quiz – prelims were conducted and of the 11 participating teams, 4 teams were shortlisted for the finals.
|Figure 2: DSI-SAARCUM Residents' Award paper session with the Judges – Prof. MPS Sawhney (Head, SGT Medical College, Gurugram), Prof. Surabhi Dayal (Head, PGIMER, Rohtak), and Dr Nayani Madarasingha (Senior Joint Secretary – SLCD, Sri Lanka)|
Click here to view
To stimulate and foster the learning potential of the delegates, DSI always holds a Pre- and Post-Test Analysis for all delegates. It included 30 questions (MCQs, Pictorial, Dermoscopic) directly related to cutaneous mycology, which were contributed by the Congress Speakers, on the premise that careful tending to their lectures would give away the answers one-by-one.
The learning points from different lectures, dialogue sessions, and workshops are presented in this paper.
Dr Rahul Sharma, Associate Professor of Community Medicine, UCMS-GTBH, New Delhi, our first speaker gave a reality check on the problem statement, through his talk on “The changing landscape of superficial mycoses in South Asia.”
- Superficial mycoses affect 20–25% of the world's population
- There has been an alarming increase in the number of “recalcitrant/resistant” superficial mycoses, from India, South Asia, and globally in the last few years
- The cases constitute the “tip of the iceberg” and there lies a substantial paucity of evidence
- The environment, host, and agent factors are responsible for the changing landscape
- Environmental factors related to global warming
- Host factors related to immunity and socioeconomic and pharmacological factors
- Agent factors related to increased resistance of Trichophyton rubrum and increased prevalence of Trichophyton mentagrophytes, a zoophilic fungus, as the co-dominant pathogen along with T. rubrum
- Public health constitutes the way forward for addressing the changing landscape, through study of region and population specific variations in fungal species and drug sensitivity patterns, assessment of socioeconomic burden, capacity building for care and antifungal stewardship by all involved stakeholders.
Dr Smriti Shrestha, Assistant Professor of Dermatology, Kathmandu Medical University, Nepal, deliberated on the aspect of “Antifungal Therapeutic Failure vs Resistance.”
- Last 5–6 years have seen a substantial rise in AFTF:
- Recalcitrant infections: persistence of clinically appreciable infection since the disease onset with none or sub-optimal response to an adequate treatment with systemic antifungal agents
- Chronic dermatophytoses: infections persisting beyond 6 months
- Recurrent infections: re-occurrence of lesions within <6 weeks of clinical cure
- Relapses: re-occurrence after 6–8 weeks of infection-free interval.
- Clinical (in vivo) resistance: failure to eradicate a fungal infection despite adequate administration of an antifungal agent with in vitro activity against the organism
- Mycological (in vitro) resistance: non-susceptibility of the fungus to standard doses of minimum inhibitory concentration (MIC) values of antifungals determined by CLSI/EUCAST (Clinical & Laboratory Standards Institute/European Committee on Antimicrobial Susceptibility Testing). In general, MIC >1 μg/ml is vaguely taken as cut-off suggestive of in vitro resistance. True drug resistance (although on a rise) contributes to a small proportion of AFTF
- Large scale and region-specific studies to define the variations in MIC levels of antifungals in dermatophytes are essential to provide data on the emergence of true drug resistance, and quantitative contribution of resistance to AFTF
- Drug pharmacokinetics and drug delivery to the site of infection might outweigh the impact of a susceptibility test result
- Itraconazole is not efficacious in the treatment of palmar and plantar dermatophytoses as drug levels achieved in sweat are negligible as compared to that in sebum
- Topical antifungals which penetrate deeper like ciclopirox olamine show better efficacy for tinea with involvement of vellus hair.
Dr Abhishek Omchery, Consultant Dermatologist, Gurugram, further elaborated on “Mycological vs clinical resistance.”
- Mycological resistance:
- Primary or intrinsic: inherently resistant strain acquired from the external milieu
- Secondary: inherently resistant variant(s) is/are selected from a heterogeneous population or the susceptible strain mutates during treatment.
- The 90–60 rule: Infections due to in vitro susceptible isolates would respond to appropriate therapy in ∼90% of cases, whereas infections due to resistant isolates would respond in ∼60% of cases.In vitro resistance may not always predict the treatment outcome
- The time frame for suspecting a resistant fungal infection, despite giving an adequate dose and duration of treatment (having ruled out immunological and extraneous factors) should be taken as 4 weeks.
Akin to all CMEs organized by team DSI, a 10-minute session of PSYCHODRAMA ROLE PLAY was held – the easiest and most effective mode of communicating a serious issue in a lighter vein. Enacted by Dr Deepak Jakhar and Dr Sidharth Sonthalia, this role play highlighted the dual consternation of skewed health awareness-empowerment of the new generation of patients, and the raging issue of topical steroid abuse contributing to antifungal therapy failures.
Dr Shukla Das, Director-Professor, Department of Microbiology and Incharge – Mycology Unit, UCMS-GTBH, Delhi enlightened everyone with less-known aspects of “Clinico-mycological evidence and host immune responses in chronic cutaneous mycoses.”
- Mycological and clinical cure as a target for complete cure should be the focus of all clinicians
- Dysregulated host immune responses are an important factor for resistant tinea infections
- The immune system tailors protective responses according to the microbial challenges, governed by different cytokines in the environment and the strength of T cell receptor –antigen interactions. Dendritic cells and CD4+ T cells can differentiate into classical Th1/Th2/Th17 or Tfh and iTreg cells
- Cell-mediated immunity can eliminate fungi but poor delayed type hypersensitivity or immune defects can prevent fungal clearance from the skin
- High IL-4 expressed due to sensitization to fungal antigen leads to high IgE (Th 1 – 2 shift), which leads to chronicity of the fungi
- IL-23 R is critical in enhancing Th17 population and promotes tissue inflammation, while Tregs maintain tolerance by their suppressive activity. However, overtly potent Tregs under the influence of TGF-β favors pathogen proliferation. These subverted Tregs may undergo a phenotype change to an alternate lineage and can polarize to Th17 phenotype. Treg/Th 17 dysregulation has a role in persistence of infection.
Dr Bhupesh Taneja, Principal Scientist, Council of Scientific and Industrial Research (CSIR) – Institute of Genomics and Integrative Biology (IGIB), New Delhi, shared the key highlights of his stupendous and ardent work on “Comparative Genomics and Virulence of Dermatophytes.
- Genome sequence analysis of dermatophytes is a step in understanding diversity of species in different parts of the world and aids in identification of virulence factors
- A steering Committee for the Fungal Genome Initiative (FGI) was created by the Broad Institute, USA in 2001 for identification and sequencing of fungi
- In vitro study done at IGIB on a resistant isolate of T rubrum, documented upregulated activity of proteases (subtilases, Sub3, and Sub14), which are the potential virulence factors. This suggested a preferential enzyme secretion under the effect of antifungal agents
- Comparative genomics may help to recognize fungal-specific genes as potential targets for diagnostics and therapy and would augment the work in areas including drug susceptibility and resistance.
Dr Kripa Shankar Gupta,Senior Consultant Pharmacologist, RARE METABOLICS, Delhi discussed “Fungal Resistance mechanisms and Biofilms.”
- Antifungal drug resistance against azoles in dermatophytes develops by:
- Modification of the drug target enzyme involved in ergosterol biosynthesis (Erg11 gene) by mutation or overexpression
- Up regulation of multidrug efflux transporters (Multi-drug resistance1 – MDR1 gene in T. rubrum)
- Cellular stress adaptation by increased transcription of genes that encode stress-response-related proteins, including heat shock proteins (Hsp90 in yeasts and molds).
- The mechanism of mutational resistance to allylamines involves a single non-silent nucleotide substitution in the gene encoding squalene epoxidase, a rare mechanism accounting for the infrequently reported resistance to these drugs
- Formation of biofilms by quorum sensing has been demonstrated by T rubrum and T mentagrophytes, which are sessile microbial communities surrounded by extracellular polymeric substances that confer additional defense against host immune response and may compromise drug efficacy
- Future directions include advances in dermatophyte gene research, exploring kinases as a target class in dermatophyte genome, studies on Hsp90 as a therapeutic target, and using natural compounds as chemo sensitizers.
Dr Pankaj Tiwary, Associate Professor of Dermatology, PMCH, Patna, dwelled upon “Etiological Factors: Beyond Steroid abuse” taking the discussion from genomics back to the clinics.
- High temperature and humidity in South Asia
- Defective host immunological mechanisms and host immunocompromised states like diabetes mellitus, obesity. Iron deficiency anemia as an important causative factor necessitating routine iron supplementation in patients with fungal infections
- Socioeconomic factors: high treatment cost, self-medication, malnutrition, overcrowding, poor hygiene, migrant populations
- Changing fashion sense with preference for tight clothing
- “Ping-pong effect” – Spread of infection within family members through sharing of clothes and footwear, hidden sites of infection, persistence of infection in household/family members/pets/fomites, and re-infections. T mentagrophyte has been found to survive on infected towels and linens for as long as 24 weeks while it is less than 16 weeks for T rubrum. Fomite disinfection is important in both cases to prevent relapses of infection
- Pharmacological factors like rampant use of topical steroids and itraconazole-related problems
- Rising drug resistance for azoles by primary and secondary mechanisms and biofilm formation.
Dr Ruchika Mehndiratta,Senior Consultant Dermatologist, Delhi-NCR spoke about the “Lacunae in our approach to a patient of cutaneous mycosis.”
- Check for the likely sources of re-infection with tinea from infected pets, beauty salons (barber/beautician), gym, and by sharing of garments and shoes between household members
- Counsel regarding preventive measures like proper washing and drying of clothes, alternate day usage of two separate footwear, avoiding vigorous rubbing during bathing which disrupts skin barrier, and avoiding usage of body nets while bathing which act as fungal reservoirs
- Rule out drug interactions that may lead to reduced bioavailability/serum levels of systemic antifungals (e.g., itraconazole with proton pump inhibitors (PPI)/H2 antagonistic drugs. The effects of longer acting PPI's like esomeprazole may persist up to 4–5 days)
- Vitamin D has immunomodulatory effects. Although, mixed opinions are there in dermatophytoses, monitoring vitamin D levels, and/or routine supplementation is recommended in patients with tinea
- A high index of suspicion for fungal infections must be kept for any shift in the pattern of an existing dermatoses or a new onset pruritus.
Dr Sidharth Sonthalia, Senior Consultant Dermatologist, Skinnocence, Gurugram and Director, Dermasource India, provided insights into Azole Menace in his lecture on “The Dark Side of Azoles Revealed.”
- The patients with tinea visiting a dermatologist are not naive, rather polypharmacy-abused in more than 90% cases, having received multiple antifungals especially oral itraconazole/topical azoles
- Oral itraconazole is often injudiciously prescribed by primary care physicians in an inadequate dose/duration or as multiple intermittent/prolonged courses
- The bioavailability/serum levels of itraconazole are influenced by other factors:
- Reduced bioavailability when co-administration with antacid medications
- Dependent on intake post meals and the effect of aerated drinks. Recent studies have shown that taking itraconazole with a cola drink does not enhance its bioavailability
- Serum levels affected by drug brand and pellet size.
- The sub-inhibitory concentrations of itraconazole achieved in patient's serum significantly increase the likelihood of secondary azole resistance by selection pressure, rendering them resistant to any further course of itraconazole, since azoles being fungistatic allow persistence of organisms
- The selection pressure-induced secondary resistance resulting from oral itraconazole is also seen to perpetuate pan-triazole and partial terbinafine and amorolfine resistance. Ciclopirox olamine is the only drug without a propensity to develop resistance
- Itraconazole-resistant strains show high levels of cross-resistance to multiple triazoles including voriconazole and posaconazole, and often to six triazole fungicides used extensively in agriculture, qualifying for multi-triazole resistance (MTR)
- Azole-resistant fungi are more virulent because of the differences in cell wall composition, increased filamentation and adherence, and enhanced biofilm formation. Once acquired, resistance is maintained even in the absence of drug
- Primary azole resistance due to their widespread use as agricultural fungicides, further adds to the azole menace. As per the statistics available from the website of the Indian Ministry of Agriculture, in the 4-year period from 2012 to 2016, there was an estimated 29.5% decrease and 34.2% increase in the consumption of insecticides and fungicides, respectively
- The spreading azole resistance in superficial fungal infections resulting in selection of a population of mutants that do not respond to any drug is likely to have graver ramifications in invasive dermatophytosis in immunocompromised individuals
- Resistance to terbinafine on the other hand, acquired through a rare mechanism, is infrequent, shows restoration of susceptibility after drug removal and has not been reported to confer cross-resistance to other antifungal agents
- The dosing of terbinafine should be as per body weight, 6 mg/kg/day and it should be given for a duration of 8 (minimum) to 12 weeks (preferred), with monitoring of liver function tests, taking into consideration the dermatophytic involvement of vellus hair.
Dr Saurabh Shah, Senior Consultant Dermatologist, Bhatia Hospital, Mumbai talked on the “Generalists – Specialists Divide,” an important issue in the problem of antifungal therapeutic failures.
- The core problem behind misuse of topical corticosteroids and injudicious use of antifungals is the deficient training of primary care physicians
- The need of the hour is to draft guidelines on the basis of evidence rather than expert consensus and to extend their benefit to the health-care personnel who treat much larger patient populations than those treated by dermatologists, through continuing medical education and training workshops for general practitioners
- Improvement in the standards of dermatology training in medical schools at undergraduate and postgraduate levels
- Intensification of efforts to reduce inappropriate prescription of corticosteroids; and their enforcement at the ground level.
Dr Deepak Jakhar, Senior Resident, Hindu Rao Hospital, New Delhi elucidated on the value of “Dermoscopy in Tinea Management” in diagnosis, choice of treatment and follow-up.
The characteristic dermoscopic features are as described:
- Onycholysis with jagged proximal margin
- Aurora borealis pattern (longitudinal striae of different colors)
- Ruin pattern (distal pulverization of nail plate)
- Fungal melanonychia.
- Comma or C-shaped hair
- Cork screw hair or coiled hair
- Broken/zig-zag/bended/angulated/deformable hair
- Black dots
- Morse-code hair and translucent hair
- More specific for ectothrix infections – morse code hair, endothrix infection – comma/cork-screw hair.
- Tinea of vellus hair – perifollicular scaling, translucent hair, bended hair, morse-code hair, corkscrew and comma-shaped hair, brown dots with whitish halo – indication for systemic antifungal treatment and aids in deciding treatment duration
- Steroid atrophy vs Tinea incognito – polygonal vessels in former while uncharacteristic in the latter. Glomerular vessels seen in steroid modified psoriasis
- Tinea pedis/mannum – localization of scales to palmar and plantar creases.
Dr Mahima Agrawal, Senior Resident, LHMC and Associated Hospitals, New Delhi provided an update on “Ciclopirox: Recalling a Forgotten Ally.”
- 1% ciclopirox olamine (CPO) cream (0.77% ciclopirox) – US FDA (United States Food and Drugs Administration) approved in 1982, and DCGI (Drug Controller General of India) approved for skin and vaginal use in 1996
- Antifungal action exerted by chelating to metal ions thereby inhibiting important enzymatic cellular process and hampering fungal cell functioning, as opposed to other topical antimycotics which act on the ergosterol pathway
- Both fungicidal and a fungistatic agent at varying concentrations
- Due to its unique mechanism of action, not even a single case of resistance reported with this molecule despite over three decades of being in use making it an ideal topical antifungal agent in the current scenario
- Broadest antifungal spectrum and used for the treatment of cutaneous dermatophytosis, cutaneous and vaginal candidiasis, seborrheic dermatitis and pityriasis versicolor among other superficial fungal skin infections
- Fungicidal even against non-growing cells, relevant in onychomycosis
- Deep penetration into hair and sebaceous glands giving reservoir effect
- Also possesses antimicrobial action against gram positive bacteria, gram negative bacteria, and protozoans, making it an excellent topical choice for macerated Tinea pedis, dermatophytosis complex (interdigital T. pedis complicated by secondary bacterial infection) and mixed vulvovaginal infections [vulvovaginal candidiasis due to Candida albicans, non-albicans candidiasis, bacterial vaginosis (inhibition of Gardnerella vaginalis), aerobic vaginitis (inhibition of Staphylococcus aureus and group B streptococci) as well as Trichomonas vaginalis]
- Potent anti-inflammatory activity, the highest amongst all topical antifungal preparations, equivalent to 2.5% hydrocortisone, which obviates the need for combined antifungal steroid preparation
- Although recently many companies have started marketing creams of CPO, it is important to note that the molecule is unstable at room temperature and requires a specific technology “S.M.A.R.T” (Stability Maintained At Room Temperature) with the aid of addition of a few specific high-melting point excipients at a crucial time-point of the formulation's emulsification process, to ensure its stability
- Thus it is imperative to use only a WHO-cGMP certified brand which provides white papers on real-time stability (×2 years) and accelerated pharmacokinetic stability (at least 6 months) data for verification.
Dr Atul M Kochhar, Consultant Dermatologist (Senior Admin. Grade), MAMC-LNJP, New Delhi moderated the Fungoral debate on “Terbinafine should be the preferred oral antifungal over Itraconazole.” Dr Shifa Yadav, Consultant Dermatologist, Kaya Skin Clinic, Gurugram presented for the motion and Dr Jitender Taneja, Consultant Dermatologist, Enhance Clinics, Gurugram presented against the motion. The salient points highlighted by the speakers to favour their position, i.e. for/against the motion have been enumerated in [Table 1].
|Table 1: Salient points presented during the Fungoral debate, both FOR and AGAINST "Terbinafine should be the preferred oral antifungal over Itraconazole"|
Click here to view
Consensus: Terbinafine is the preferred systemic antifungal of choice for dermatophytic infections. Itraconazole should be the second choice, if indicated, for cases not responding to terbinafine.
Dr Ishmeet Kaur, Senior Resident, ESIPGIMER, Basaidarapur, New Delhi spoke on “Miscellaneous antifungal drugs: Old wines in new bottles.”
- With an emerging resistance to commonly used antifungals, the older less commonly used drugs come into play. The newer drug formulations include micelles, transferosomes, nanoparticles, nanostructures, microemulsions, and liposomes
- Topical allylamines: Naftitine is FDA approved for pediatric age groups of >2 years. Butenafine and tolnaftate have anti-inflammatory and antibacterial actions with once a day application and require shorter treatment course
- Amorolfine is now available in cream preparation for tinea and candidal infections. It is better than azoles, since it acts at two steps of ergosterol synthesis inhibition
- Fenticonazole has role in vulvovaginal candidiasis and is effective against dermatophytes and yeasts. It has two added mechanisms of action with activity against cytochrome oxidase and proteases, proven only in Candida species
- Whitfield ointment has fungicidal and keratolytic activities and has potential role in cases resistant to both azoles and allylamines
- Other older topical agents with present utilities are nystatin, gentian violet, selenium sulfide, and povidone iodine
- Griseofulvin is an older systemic antifungal agent that has good efficacy and safety profile in children with Tinea capitis caused by Microsporum species
- Oral ketoconazole was the first available broad spectrum antifungal and can be used in extensive or recalcitrant dermatophytosis
- The agents which have been proposed to be used in combination with antifungals for their synergistic action or to prevent resistance are – antibiotics like doxycycline, azithromycin and minocycline, retinoids, statins, and calcineurin inhibitors. But their practical application awaits more evidence.
Dr Pravesh Yadav, Assistant Professor, LHMC and Associated Hospitals, New Delhi discussed on “Basic Essentials of Quality Control of the prescription topicals”
With an availability of over 175 brands of itraconazole, there is a heightened awareness regarding its varying efficacy. Similar concerns also exist with topical antifungal agents. According to the World Health Organization (WHO) report, 10% of the topical formulations available in India are of sub-standard quality.
- WHO-cGMP (World Health Organization – companies Good Manufacturing Process) accreditation status of the manufacturing unit is essential to ensure efficacy and stability of a topical product.
- Quality control procedures include:
- Real-time stability testing: Done at – 25 ± 2°C/60 ± 5°C relative humidity. To evaluate the stability of the drug under normal storage conditions expected in the intended market, for selection of adequate formulation and determination of shelf life. Requires a periodic testing of over at least 24 months
- Accelerated time study: Done at –40 ± 2°C/75 ± 5°C relative humidity. To assess stability at extremes of physical conditions and to evaluate the impact of short-term excursions outside the label storage conditions e.g., during transport.
Dr Manjul Agrawal, Consultant Dermatologist and Hair Restoration Surgeon, Fortis Hospital, Delhi and Dr Ramanjit Singh, Senior Consultant Dermatologist, Medanta – The Medicity, Gurugram moderated the session on “Dialogues from Across the Globe ” with the following panelists:
The following issues were addressed:
- The problem of recalcitrant cutaneous mycoses is a major epidemic across all South Asian countries
- The use of oral itraconazole has indeed made the situation worse
- The countries share a lack of public awareness and counseling the patients about general measures is of paramount importance
- Terbinafine continues to give good results. Non-availability of ciclopirox olamine is an issue in some of the South Asian countries
- Experience with alternative treatments with natural products, phototherapy, and lasers is mostly lacking in all countries
- There is a need for multicentric studies to determine anti-fungal susceptibility patterns across South Asia. SAARCUM must be formalized as a registered international forum for further such discussions.
Dr Sangeeta Verma, Senior Consultant Dermatologist, Gurugram presented a talk on the utility of “Light therapy: PDT, UVR and more.”
- Innovative approach to treatment in cases of drug resistance, poor candidates for oral antifungal therapy, and patients non-responsive to multiple topical antimycotics
- Photodynamic Therapy – Systemic/topical photosensitizers (chlorines, porphyrins, phenothiazines, phthalocyanins) are given along with illumination (optimal wavelength – 410 nm) of a target lesion. Acts by oxidative photodamage at the site. Light penetration in blue region is 1.5 mm and red region is 3 mm. Although it is available at handful of centers in India, they are being used by oncologists
- Ultraviolet Therapy – UVB light shows maximum efficacy in inhibition of both T. rubrum and T. mentagrophytes. Studies show good efficacy in cases of pityriasis versicolor and seborrheic dermatitis. Acts by releasing a variety of pro-inflammatory and immunosuppressive cytokines and anti-microbial peptides from keratinocytes and T-cells. Vitamin D produced during phototherapy may also be responsible
- Light-emitting diode (LED) therapy – Exposure at 280 nm, with a fluence of 0.5 J/cm2 showed inhibitory effect on T rubrum, indicating its potential role as a low-cost in home treatment or disinfection method
- Sun Therapy – Used for interdigital tinea pedis not responding to topical antifungals. Boosted solar therapy given by using simple convex hand lens (focal length 20 cm, diameter 9.5 cm), held at 17 cm to focus the solar radiation on the infected area for 30–50 s. Complete clinical cure was achieved by 17th day and no relapse was observed at 4 months follow up.
Dr Aman Sharma, Senior Consultant Dermatologist & Holistic Healer, Gurugram elaborated on the role of “Pharmacological/botanical approaches in breaking the biofilm.”
- Phytoceuticals have been utilized as alternative approaches in breaking fungal biofilms
- Propolis, also called royal jelly, a honey bee product has broad spectrum anti-fungal effects with nail penetration of >2 mm. Possible role in overcoming azole resistance and inhibiting pre-formed and developing biofilms. Available as Apidermin moisturizing cream (propois + vitamin A). Limiting factors are high cost and irritant potential
- Essential oils – used in 1:10 dilution with coconut oil once/twice a week e.g., cinnamon oil, origanum, marjoram, Marichadi oil (pepper and other herbs in mustard oil)
- Oral curcumin and topical application of turmeric oil have potent antifungal action against dermatophytes, yeasts, and molds
- Apple cider vinegar taken orally or used as oral swishes or topical application has antifungal action against candida species.
Dr Amarendra Pandey, Senior Consultant Dermatologist & Laser Surgeon, Jabalpur shared his experience of using “Light and lasers for breaking the biofilm.”
- US-FDA approved lasers for onychomycosis (OM) include:
- Long pulsed Nd: YAG 1064-nm laser,
- Q-switched Nd:YAG 1064- and 532-nm Nd:YAG lasers,
- Carbon-dioxide (CO2) laser and
- Near-infrared diode laser.
- Mechanism of action –
- Nd:YAG lasers act by selective photothermolysis. Fungal chromophore – xanthomegnin (532 nm)/melanin (1064 nm)
- CO2 lasers – photothermal effect. Micro-holes made by fractional CO2 laser may improve the penetration of the topical antifungal agent into the nail bed
- Other mechanisms – effect on cell metabolism, such as reducing membrane permeability and generating reactive oxygen species (ROS) from mitochondria. Thermal disruption of biofilms.
- Studies show a mycological cure rate of 11%, using patients as a unit of analysis and 63% using nails as the unit of analysis. Complete cure (mycological cure and 100% clear nail) was found to be 50% using nails as the unit of analysis
- Quick and easy procedure. No consumables, so affordability can be customized
- Steps for the use of Helios III®– a fractionated QSNd:YAG nanosecond laser with separate fractional 532 hand piece modality in OM was demonstrated in the workshop:
- Fractionated 1064 Free Running (FR) mode – 1500–2000 J, 4–5 passes dependent on patient tolerability<
- Zoom hand piece – 1064 nm – spot size – 5 ->4 ->3 – circular motion – multiple passes – 1200–1500 J in FR mode. End point – mild white change in color
- Zoom hand piece – 1064 nm – spot size – 5 – nano second pulse – energy 700–900 J – endpoint deep white ppt – in extensive cases
- Fractional 532 hand piece – defocussed energy from 2–3 cm away – 160–200 J – dependent on patient tolerability.
Dr Kalpana Patel, Senior Consultant Cosmetic Dermatologist, Gurugram presented her innovative work on “Chemical Peels for Onychomycosis.”
- Nail peeling can be combined with topical antifungal agents for toe nail onychomycosis, in patients who are not the candidates for oral therapy
- The use of Black Peel, a combination peel was demonstrated in the workshop. The constituents:
- 8% black acetic acid (antimicrobial and antifungal activity against dermatophytic and candida infections and breaks biofilm),
- 20% salicylic acid (enhances penetration of other peel agents, antimicrobial, and antifungal action)
- Jasmonic acid (antifungal)
- Bio-Sulphur (antifungal)
- Potassium iodide (broad-spectrum antiseptic and disinfectant activity).
- The nail folds and cuticles were occluded with vaseline and a uniform coat of combination peel was applied over the infected toe nails, followed by a second coat 20 min later. After 40 min, the peel was washed off with distilled water followed by application of 8% ciclopirox olamine (CPO) or amorolfine nail lacquer
- Peel sessions, given weekly for 4 weeks and fortnightly for the next 4–6 months with daily self-application of CPO lacquer by the patient at night have shown clinical improvement at 4 weeks and complete mycological cure by 6 months. The first report of cure of toe nail onychomycosis with this protocol has been recently published.
Dr Jyoti Bhaskar, Senior Consultant Gynecologist and Obstetrician, Max Super Specialty Hospital, New Delhi spoke on “Approach to treatment in Vulvovaginal Candidiasis.”
- 70–75% women in child-bearing age group have at least a single episode of vaginal discharge with a diagnosis of vulvo-vaginal candidiasis (VVC) in 40–60% cases. Recurrent VVC (RVVC) is becoming a nightmare for patients and doctors alike
- Culture and wet microscopy is essential for diagnosis of recurrent thrush
- Risk factors for RVVC – Pregnancy, immunocompromised states like diabetes and human immunodeficiency virus infection. Iron deficiency is an often ignored factor that must be looked for and corrected
- Induction and maintenance therapy is the preferred treatment as recommended by all international guidelines. Induction phase: Tab fluconazole 150–200 mg, 3 doses 72 h apart. Maintenance phase: 6 months of weekly fluconazole is the most commonly recommended treatment. The suspected efficacy is only 42.9% after 12 months
- Indian data clearly shows increased azole resistance and appearance of non-albicans candida species (esp. C glabrata) in VVC. Hence, every case of recurrent VVC should be evaluated by a culture and in vitro susceptibility testing should be used to guide the treatment especially for non-albicans candidiasis
- Ciclopirox olamine, boric acid suppositories (600 mg once a day for 14 days) offer better clinical and mycological cure rates than azoles as proved in various studies. Boric acid vaginal tablets are not yet available in India. Although they can be easily procured through the internet as “pH-D” vaginal suppositories
- Intimate hygiene washes may alter normal vaginal flora and increase local dryness and are not preferred for routine usage
- Probiotics with Lactobacillus acidophilus, L rhamnosus, and L reuteri may offer short-term benefits.
Dr Lipy Gupta
, Senior Consultant Dermatologist, New Delhi and Dr Monica Bambroo
, Senior Consultant and Head of Dermatologyt, Artemis Hospital, Gurugram, moderated the session on “Dialogues from across Specialties
” with following panelists:
The key highlights of the session were:
- In tinea patients with multiple comorbidities, terbinafine and fluconazole are preferred systemic antifungal agents. Itraconazole is the only affordable treatment option for invasive fungal infections and should not be used for superficial mycoses
- Baseline liver function tests repeated after 6 weeks of therapy are recommended for systemic antifungal treatment. Preferred oral treatment for a patient of erythrodermic tinea with deranged liver functions – terbinafine with hepatoprotective agents such as silymarin 140 mg BD and/or S-adenosylmethionine (SAM) 400 mg BD, with close monitoring of liver functions
- Terbinafine oral granules are US-FDA approved for use in Tinea capitis in children aged ≥4 years and griseofulvin for >2 years. Due to non-availability of terbinafine oral granules in South Asia, the 250 mg tablet has to be divided or 125 mg dispersible tablet can be used
- Dermoscopy is a useful method for dermatophytic diagnosis and avoids scraping related anxiety in children
- Topical antifungals are preferred for treatment of fungal infections in pregnant women. Ciclopirox olamine cream obviates the need for topical steroids due to its potent anti-inflammatory activity
- Oral terbinafine is pregnancy category B and can be used in extensive cases, especially after 1st trimester
- Dermatologists often tend to underestimate the psychological disturbances (depression, anxiety) present in patients with complicated tinea. Psychological well-being must be an important consideration in patients with chronic and recalcitrant dermatophytoses
- Patient Health Questionnaire-9 (PHQ-9) score, a 2-min OPD evaluation can be easily used in every skin clinic to assess patient's reaction to the problem and the need for psychiatry consult
- Escitalopram and desvenlafaxine are the newer anti-depressant medications that can be safely used with lesser risk of side-effects and drug interactions and a rapid response within 1–2 weeks.
[Figure 3] gives a glimpse into the scientific proceedings of the Congress.
The Congress concluded with the Quiz Finale in which the four Quiz teams that were shortlisted after the Prelims fought it out for the crown [Figure 4].
|Figure 4: Postgraduate Quiz Prelims and Finale with Quiz masters – Dr Poonam Sharma (Senior Consultant, SISD, New Delhi) and Dr Sushruta Kathuria (Specialist, VMMC-Safdarjung hospital)|
Click here to view
- Formalization of DSI-SAARCUM into a registered organization with a set of goals and deadlines for regional cooperation
- Regional multicentric in vivo and in vitro trials to be planned to generate evidence on antifungal susceptibility patterns with inter-specialty collaboration
- Nationwide and South Asian Corporate Social Responsibility (CSR) ventures, with Union Ministry of Health funding and logistics support on Flagship program of “Dermatology for All,” that would undertake three responsibilities:
- DERMATOLOGY UPDATES: CME's conducted by Dermatologists to train the GPs in a controlled way – sharing with them the protocols of ensuring cure for tinea patients including a complete stoppage of prescribing steroid-based topicals; while also telling them about the red herrings for referral to dermatologist
- DSI TAFOSTASAG-0: The DSI Task Force to Stop Abuse of Steroid topicals At Ground Zero – Random checks conducted at as many pharmacies as possible to identify the defaulters and warn/punish them through proper channel
- DSI-IST TELEDERMATOLOGY INITATIVE: In absence of any current guidelines, DSI, in alliance with the International Society of Teledermatology has formulated a Programme of Action of materializing this potential tool, to extend the benefit to distant and offshoot areas.
Overall, the First International Congress of SAARCUM not only apprised the delegates of the reasons underlying the failure of our attempts to contain the fungal epidemic, the take home messages from the talks included the proper approach to a patient with tinea and ideal management, pharmacological as well as non-pharmacological. More importantly, the Congress served the purpose of bringing together Dermatologists from South Asian countries and physicians from other specialties to join hands and strategize to defeat the menace as a dedicated alliance.
The authors would like to thank all the eminent faculty members for their contribution.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]