Abstract: The researcher identified how each pharmaceutical drug, griseofulvin and terbinafine, affects tinea capitis. Background: Tinea capitis is a dermatological infection common in children of African descent.1 Additionally, the optimal conditions for the fungus to spread are in warm, moist temperatures.2 Although, Trichophyton tinea capitis is controlled, it is becoming more common in urban areas. There are many treatment options for Trichophyton tinea capitis. Treatments of tinea capitis include itraconazole, fluconazole, and terbinafine.5 However, the literature review examined specifically if griseofulvin or terbinafine is a better treatment for Trichophyton tinea capitis. Conclusion: After review, despite previous findings, the author concluded that terbinafine is the superior option compared to griseofulvin in treating Trichophyton tinea capitis, which is easily contracted. Providing the optimal treatment to patients gives them power and autonomy over their health; moreover, the terbinafine impacts the community by relieving the symptoms and curing Trichophyton tinea capitis.
Introduction
Tinea capitis is a dermatological infection common in children of African descent(1). The pediatric fungal infection is common within urban areas and is characterized by scaling and dry, itchy skin(1) The infection is caused by dermatophytes, a fungus found on dead skin cells(2). Tinea capitis may develop if hair goes unwashed or is wet for an extended period of time(2). A small injury to the scalp could also cause the fungus to infect the skin(2). The optimal conditions for the fungus to spread are in warm, moist temperatures(2).
The fungal infection is present throughout the world, and has become more frequent in countries such as the United States of America and Ethiopia(3). Different environments are more prevalent to different types of tinea capitis which cause infection(3). Trichophyton and Microsporum are two genera that characterize the fungal infection(3). Trichophyton species is specific and prevalent to North America, while Microsporum is common to Europe and Africa(3). Although, Trichophyton tinea capitis is controlled, it is becoming more common in urban areas. There are many treatment options for Trichophyton tinea capitis. The various medications provide patients with the power and autonomy over their health. These treatments are offered via oral granules or tablets.
Griseofulvin is the primary oral medication used to treat tinea capitis, specifically Trichophyton species.4 Griseofulvin, also referred to as the “gold standard”, has been the top medication prescribed to patients for more than 50 years(4). However, Trichophyton is becoming resistant to griseofulvin, as indicated by the need to increase dosage, length of treatment, and the number of times the medication is taken weekly(4). Sulfide or ketoconazole shampoo is also prescribed as an adjunct medication to ensure a successful treatment, as well as to stop the spread of infection(5).
Other treatments of tinea capitis include itraconazole, fluconazole, and terbinafine(5). According to Elewski,5 itraconazole is an effective treatment that is provided as a liquid; however, the treatment is not well received in healthy children. Itraconazole also has an adverse effect of severe diarrhea in children(5). The treatment lasts about 4-6 weeks for a complete cure(5). Fluconazole is another treatment of Trichophyton tinea capitis. Elewski5 states fluconazole is a safe medication with an 89% complete cure rate; however, according to Chander and Manchanda(6) the duration of the complete cure is 10 weeks. Both itraconazole and fluconazole are not as effective as griseofulvin, because of adverse effects and length of treatment, respectively. Terbinafine, however, is a superior drug compared to griseofulvin when treating Trichophyton tinea capitis(5). Itraconazole and fluconazole treatment medications are available; however, they do not fulfill the following criteria established for the most effective treatment.
A complete cure is necessary to evaluate the degree at which the treatment is successful or effective. Complete cure is included among the set criteria to determine efficacy of treatment. Complete cure is defined as a combination of mycological cure and clinical cure(1). Furthermore, mycological cure is characterized by negative fungal culture(1) Clinical cure is the absence of any physical signs of dermatophyte on the scalp(1). The criteria for a safe, effective treatment of Trichophyton tinea capitis include moderate to exceptional progress of complete cure of infection, superior rate of cure, and mild adverse effects. Mild adverse effects are acknowledged by the severity of the adverse effect and whether treatment needs to be discontinued. Moderate improvement indicates average improvement of symptoms (about 50% cure), and exceptional improvement (60%-100%) signifies an above average improvement of the treatment duration criterion. Griseofulvin and terbinafine both meet the criteria; however, terbinafine produces better results in a shorter amount of time.6
Complete Cure
A complete cure is necessary for the improvement of Trichophyton tinea capitis. Many studies measured the complete cure by identifying the mycological cure and clinical cure. As previously stated, an indication of a successful treatment option, results in a complete cure of at least 50%. Studies administered medication based on weight of patients at high dosages of griseofulvin (15-25mg/kg). The studies included did not test the medications with any adjunct medication, such as sulfide shampoo.
The confidence interval and p-values were statistically calculated to conclude which medication was more effective in terms of complete cure. A confidence interval creates a range in which the probability of a result is likely to occur. In each study a confidence interval cannot cross 1 on the number line; therefore, if the range crosses 1, the comparison of data is not significant. P-values determine if a comparison of data is significantly different from one another if the value is less than 0.05. According to Chander and Manchanda, (6) 24/25 patients who received griseofulvin had a complete cure (96%); however, the patients received two high doses of 15-25mg/kg/day. The increased dosage compared to the other medications resulted in biased data. Additionally, Chander and Manchanda (6) prescribed the third group terbinafine, which had an 88% complete cure. Chander and Manchanda(6) had confidence interval of 0.92-1.38 and a p-value of 0.609 indicating there is no significant difference between the two treatments. Both medications resulted in similar complete cures.
In randomized, controlled study, Elewski3 et al combined multiple trials and concluded the complete cure for griseofulvin was 39% (170/434). Griseofulvin had a complete cure of 34.01% (67/197) in trial 1; similarly, the complete cure in trial 2 was 43.46% (103/237). The study determined the concentration of medication for each child based on weight. Children 10kg to 40kg received 62.5mg to 125mg respectively(3). The majority of patients received 19.9mg/kg/day of griseofulvin. Within the randomized controlled test, Elewski et al3 recorded the complete cure at 45.1%. The study indicated between the two groups tested that trial 1 had a 46.23% effectiveness of complete cure and trial 2 had 43.99%.3 There was a significant difference between the two treatments in trial one, but similar complete cures in the second trial. According to Elewski et al(3), terbinafine was statistically significant overall regarding complete cure compared to griseofulvin (P < 0.05). Out of the two trials, the first trial had a recorded p-value of 0.01 indicating significant difference in complete cure. The second trial, however, was not significantly different with a p-value of 0.95.3
In a study lead by Dastghaib et al,(7) griseofulvin was observed to have a 76% complete cure (13/17) with 17 patients that had Trichophyton tinea capitis. Deng et al(8) recorded clinical cure and mycological cures from ranges 80%-100% prescribing griseofulvin for all Trichophyton species of tinea capitis. Though the study did not measure complete cure, it measured the two components that made up the complete cure. Three groups were tested in the study and each group was treated for a specific duration of time with the medication. Clinical and mycological cures almost reached 100%,8 indicating a successful efficacy rate; however, the increase of complete cure might have been an error. Results as high as 100% are infrequent, particularly when testing griseofulvin within 8 weeks as the study had done. The medication prescribed to treat Trichophyton tinea capitis in other studies also showed successful rates of complete cure. Many studies demonstrated the efficacy of terbinafine curing Trichophyton tinea capitis with similar or exceptional progress regarding complete cure. Hamm et al(9) stated a 64% complete cure when testing terbinafine on Trichophyton tinea capitis species. Each patient was prescribed terbinafine based on the patient’s weight. Children weight range was from 10kg to over 40kg while the medication ranged from 62.5mg to 250mg respectively. Friedlander et al10 found a 42%, 49%, and 56% complete cure within different durations of time for terbinafine. Therefore, as more time passes, terbinafine becomes more effective in treating the fungal infection. The concentration of medication based on weight was identical to the dosage distribution in the study performed by Hamm et al.(9) A confidence interval was generated from a study performed by Tey et al(12) and the complete cure as 95%. The recorded confidence interval (CI), 0.785-1.919, indicated no significant difference between the two treatments which demonstrates the same efficacy of the two medications. The p-value also identified that there was no statistical significance between griseofulvin and terbinafine within the overall analysis (P = 0.37)(12). Each medication has effective cures for Trichophyton tinea capitis. Some studies identified increasing complete cures, while others found lower complete cures for both griseofulvin and terbinafine. Terbinafine is another alternative in treating children with Trichophyton tinea capitis.5 Both treatments cured Trichophyton tinea capitis; however, they each differed in the rate at which it cured the fungal infection.
Rate of Improvement
The rate at which Trichophyton tinea capitis is cured provides critical information on the conclusion of which medication is superior. Since griseofulvin and terbinafine both cure Trichophyton tinea capitis with the same efficacy, the rate of improvement is the concluding factor. Chander and Manchanda(6) recorded complete cure within 6 weeks using griseofulvin. Four patients out of 25 total in the group were given an extended 7-8 weeks of treatment(6). Additionally, Chander and Manchanda6 recorded complete cure within 2 weeks after administering terbinafine to the 25 person group; however 3 patients were not cured. Other studies including the study performed by Dastghaib et al7 concluded complete cure within 8 weeks (76% cure).
Deng et al(8) measured the duration of treatment for 2, 4, and 8 weeks with dosage ranging from 62.5mg to 125mg determined by weight. The highest complete cure resulted within the 8 weeks to 1-year duration(8). Complete cure increased based on duration of treatment; however, after 8 weeks the complete cure was 100%. The statistics favor griseofulvin compared with terbinafine. According to Deng et al,(8) an effective treatment for Trichophyton tinea capitis is 2-4 weeks indicating 2 weeks is an adequate length of time for treatment. The complete cure was exceeding 80%; however, as previously stated error was included based on the integrity of the children and their families to report observations on time and to be truthful about improvement. Error is highly suspected, since other 8-week duration treatments did not obtain similar results compared to other studies.
Tey et al(11) observed studies that tested griseofulvin for a complete cure within 6-12 weeks, with an average of 8 weeks. Tey et al(11) also reported a mean treatment duration of 4 weeks administering terbinafine with a 2-6-week range. Furthermore, a review written by Chan and Friedlander(12) mentions the average duration of treatment for griseofulvin is 6-8 weeks and a duration of treatment for terbinafine in 2-4 weeks. Sulfide or ketoconazole shampoo are most commonly used as adjuncts to griseofulvin;5 however, without the adjunct medication griseofulvin treats Trichophyton tinea capitis within a 6-8-week time period.6,7,8,11,12 Terbinafine has the same dosage concentration and possibly lower in some cases. Friedlander et al10 states 2- and 4-week durations of administering terbinafine reveals more improvement than the first week of administering medication. Most comparative studies report that 4-week duration with terbinafine is the equivalent to an 8-week duration using griseofulvin.10 Hamm et al9 concluded 2 weeks are required for Trichophyton tinea capitis to cure most patients. Dependent on the severity of the condition, terbinafine commonly treats Trichophyton tinea capitis within a 2-4-week duration.
Many studies compared 6-8-week treatment of griseofulvin with 2-4-week treatment with terbinafine and concluded griseofulvin was better because of a superior complete cure value. Although, the majority of studies indicate the two treatments are both efficacious, the optimal treatment to improve symptoms of Trichophyton tinea capitis, in regard to rate of cure, is terbinafine.
Adverse Effects
Adverse effects (AEs) are critical in determining the right treatment for a patient. The severity and intensity of AE predicts how the medication will affect the patient and may cause more harm. Adverse effects were recorded based on observation, test results, and the patient’s integrity to communicate with the researcher. Griseofulvin could cause a number of AEs such as headache, respiratory problems, and gastrointestinal symptoms, which include abdominal pain, diarrhea, and vomiting(11).
Similarly, Dastghaib et al7 stated griseofulvin had an AE of nausea; however, the AE was not severe and discontinuation of treatment was unnecessary. Tey et al(11) concluded that the studies analyzed did not include severe adverse effects while testing griseofulvin. Terbinafine use could result in similar AEs of griseofulvin. Tey et al(11) reported the same AEs for terbinafine as griseofulvin. Chan and Friedlander(6) stated the most common AEs for terbinafine within the analysis of the comparative study were headache, rash, and gastrointestinal symptoms. The study also states that the medication can be excreted with breast milk; therefore, mothers who are nursing should not be prescribed terbinafine(6). Friedlander et al(10) had 44% of patients report mild to moderate AEs with the study including respiratory and gastrointestinal symptoms, which were the most frequent. One patient had to discontinue treatment for a severe AE, which was an uncommon case. Hamm et al(9) states terbinafine is a safe, effective medication for patients; similarly, the other researchers have concluded the same thing. Terbinafine and griseofulvin could both cause the patient to experience AEs, specifically respiratory and gastrointestinal symptoms. However, the AEs experienced are commonly mild to moderate and infrequently severe. Elewski et al(3) concluded from the studies analyzed, that nasopharyngitis, headache, and pyrexia were the most common AEs for both griseofulvin and terbinafine. Discontinuation of treatment for most studies were uncommon.3 Deng et al(8) determined both griseofulvin and terbinafine were safe treatments indicated by AEs. Both griseofulvin and terbinafine produce minimal mild to moderate AE.
Conclusion
The criteria require a treatment with moderate to exceptional progress of complete cure, superior cure rate, and mild adverse effects. Based on the criteria set for the optimal medication to treat Trichophyton tinea capitis, terbinafine is superior to griseofulvin. The studies that concluded exceptional progress of complete cure (X > 50%) prescribed high dosages of griseofulvin (20-25mg/kg/day) and longer duration of treatment. Terbinafine, although treated with the same concentrated dosage, only required 2-weeks of treatment with similar complete cure, which indicates terbinafine is the superior treatment. Both had similar side effects that did not influence discontinuation of treatment. Each study tested was safe and treats patients similarly, the critical difference is that terbinafine obtains the same results in a shorter amount of time. Most studies concluded that griseofulvin was the superior and recommended treatment because of cost, but the decreased duration should save money. Furthermore, the shorter treatment duration would help children and parents get rid of the fungal infection sooner decreasing the chances of children irritating the area or suffering from the infection. Overall, since terbinafine is superior over griseofulvin, the medical staff is able to provide an impactful treatment to patients. The optimal drug allows for a shorter treatment period, which restores patients back to their state of health before the infection.
References
1. Lorch Dauk KC, Comrov E, Blumer JL, O'Riordan MA, Furman LM. Tinea capitis: predictive value of symptoms and time to cure with griseofulvin treatment. Clin Pediatr. 2010;49(3):280-286. doi:10.1177/0009922809338313.
2. DynaMed Plus. Ipswich (MA): EBSCO Information Services. 1995 - Record No. 116543, Tinea capitis. http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=116543. Updated 2016 Aug 26. Accessed February 12, 2018.
3. Elewski BE, Caceres HW, DeLeon L, Shimy SE, Hunter JA, Korotkiy N, et al. Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomized, investigator-blinded, multicenter, international, controlled trials. J Am Acad Dermatol. 2008;59(1):41-54. https://doi.org/10.1016/j.jaad.2008.02.019.
4. Shemer A, Plotnik IB, Davidovici B, Grunwald MH, Magun R, Amichai B. Treatment of tinea capitis - griseofulvin versus fluconazole - a comparative study. J German Soc Dermatol. 2013;11(8):737-741. doi:10.1111/ddg.12095.
5. Elewski BE. Treatment of tinea capitis: beyond griseofulvin. J Am Acad Dermatol. 1999;40(6):27-30. https://doi.org/10.1016/S0190-9622(99)70394-4.
6. Chander G, Arora P, Manchanda V. Comparative evaluation of griseofulvin, terbinafine and fluconazole in the treatment of tinea capitis. Int J Dermatol. 2012;51(4):455-458. https://doi-org.gate.lib.buffalo.edu/10.1111/j.1365-4632.2011.05341.x. Published March 21, 2012. Accessed March 20, 2018.
7. Dastghaib L, Azizzadeh M, Jafari P. Therapeutic options for the treatment of tinea capitis: griseofulvin versus fluconazole. J Dermatol Treatment. 2005;16(1):43-46. doi:10.1080/09546630510025932.
8. Deng S, Hu H, Abliz P, Wan Z, Wang A, Cheng W et al. A random comparative study of terbinafine versus griseofulvin in patients with tinea capitis in western China. Mycopathologia. 2010;172(5):365-372. doi:10.1007/s11046-011-9438-2.
9. Hamm H, Schwinn A, Brautigam M, Weidinger G. Short duration treatment with terbinafine for tinea capitis caused by Trychophyton or Microsporum species. Br J Dermatol. 1999;140(3):480-482. https://doi-org.gate.lib.buffalo.edu/10.1046/j.1365-2133.1999.02713.x. Published December 24, 2001. Accessed March 20, 2018.
10. Friedlander SF, Aly R, Krafchik B, Blumer J, Honig P, Stewart D. Terbinafine in the treatment of Trychophyton tinea capitis: a randomized, double-blinded, parallel-group, duration-finding study. Pediatrics. 2002;109(4):602-607. file:///C:/Users/Brian/AppData/Local/Packages/Microsoft.MicrosoftEdge_8wekyb3d8bbwe/TempState/Downloads/Terbinafine_in_the_treatment_o.PDF. Published April 2002. Accessed March 13, 2018.
11. Tey HL, Leong Tan AS, Chan YC. Meta-analysis of randomized, controlled trials comparing griseofulvin and terbinafine in the treatment of tinea capitis. J Am Acad Dermatol. 2011;64(4):663-670.https://doi.org/10.1016/j.jaad.2010.02.048.
12. Chan YC, Friedlander SF. New treatments for tinea capitis. Curr Opin Infect Dis. 2004;17(2):97-103. doi:10.1097/01.qco.0000124362.27345.0f.