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Tinea Capitis: Predictive Value of Symptoms and Time to Cure With Griseofulvin Treatment

Clinical Pediatrics 49(3) 280–286 © The Author(s) 2010 Reprints and permission: http://www. DOI: 10.1177/0009922809338313

DOI: 10.1177/0009922809338313 Kelly C. Lorch Dauk, MD, 1 Elana Comrov, MD, 1

Kelly C. Lorch Dauk, MD, 1 Elana Comrov, MD, 1 Jeffrey L. Blumer, PhD, MD, 1 Mary Ann O’Riordan, MS, 1 and Lydia M. Furman, MD 1

Abstract Objectives. To describe (a) the predictive value of symptoms for diagnosis of tinea capitis and (b) the rate and timing of cure with high-dose griseofulvin treatment. Methods. This prospective open-label study enrolled children aged 1 to 12 years with clinical tinea capitis. Participants with a positive dermatophyte culture received oral griseofulvin (20-25 mg/kg/day) and topical selenium sulfide shampoo for 6 weeks. Main outcome measures. The rate of symptoms of tinea capitis, and rates of mycologic and clinical cure. Results. The positive predictive values of any 1, 2, 3, or 4 symptoms for a positive culture were 88%, 82%, 78%, and 77%, respectively.The observed rates of mycologic, clinical, and complete cure were 89%, 66%, and 49%, respectively. Conclusion. In a high-risk population it is reasonable to diagnose tinea capitis using one or more cardinal symptoms. Oral griseofulvin at 20 to 25 mg/ kg/day with adjunctive shampooing for 6 weeks is moderately successful as treatment.


tinea capitis; griseofulvin; mycologic cure

Tinea capitis is a common pediatric dermatophyte infec- tion characterized by scaling and patchy alopecia of the scalp. It has a symptomatic prevalence rate of 3% to 8% in inner-city school children and an asymptomatic or carrier state prevalence ranging from 5% to 44%. 1-7 Historically, the predominant agent responsible was Microsporum, which could be identified with a fluo- rescent Wood’s lamp. Over the past 40 to 50 years, Trichophyton tonsurans has emerged as the primary agent accounting for >95% of positive cultures in the United States. 7-11 Because Tricohphyton species are not fluorescent, clinicians must rely on culture, clinical pre- sentation, or microscope exam of hair debris for diagnosis of tinea capitis. Recent literature has supported the util- ity of clinical signs and symptoms in evaluation for tinea capitis, and we sought to confirm those criteria and expand their applicability. 12 Griseofulvin remains the most widely prescribed antifungal for tinea capitis, and until September 2007 was the only US Food and Drug Administration (FDA) approved treatment. 11,13 A recent Cochrane Review con- cluded that newer treatments such as terbinafine “may be similar to griseofulvin in [the treatment of] children with tinea capitis caused by T. tonsurans species.” 13 The

shorter duration of treatment with terbinafine may pro- mote compliance, but cost is higher and longer treatments are being tested. 14-16 The American Academy of Pediat- rics recommends a single daily dose of “10-20 mg/ kg/day of microsize griseofulvin (or 5-10 mg/kg/day of ultrasize griseofulvin) for 4-6 weeks” with the option of continuing treatment for 2 weeks beyond clinical resolu- tion. 17 The need for longer treatment duration and higher dosing followed reports of treatment failure, with up to 39% of patients considered nonresponders; many clini- cians use a dose of 20 to 25 mg/kg/day of microsize griseofulvin for 6 to 8 weeks based on informal expert recommendations. 18-20 Although this higher dosage regi- men is widely believed to be effective, there is sparse data establishing rates of mycologic and clinical cure and duration of therapy required.

1 Department of Pediatrics, Rainbow Babies and Children’s Hospital, Cleveland, Ohio.

Corresponding Author:

Lydia M. Furman, MD, Division of General Academic Pediatrics, Rainbow Babies and Children’s Hospital, Department of Pediatrics, Room 784, MS 6019, 11100 Euclid Avenue, Cleveland, OH 44106 E-mail:

Lorch Dauk et al.


Our first objective was to evaluate the predictive value of symptoms of tinea capitis for a positive derma- tophyte culture in a general pediatric population at risk for tinea capitis. Our second objective was to determine the rate and timing of mycologic and clinical cure during a 6-week treatment with 20 to 25 mg/kg/day of oral griseofulvin and twice weekly shampooing with 2.5% selenium sulfide shampoo.


Study Design

This was a prospective unblinded intervention study. The study was approved by the Institutional Review Board of University Hospitals Case Medical Center.


The population included children aged 1 to 12 years seen at the Pediatric Practice of Rainbow Babies and Children’s Hospital with a clinical diagnosis of tinea capitis (“ringworm of the scalp”). Inclusion criteria were the following: clinical symptoms compatible with tinea capitis, presence of a legal guardian at the visit, and a health provider who notified the study nurse of the patient. Exclusion criteria were the following: known sensitivity or allergy to griseofulvin, known liver dis- ease, kidney disease or blood dyscrasia that could alter metabolism of griseofulvin, pregnancy, known immuno- compromise, or current receipt of other antifungal agent.


The Pediatric Practice of Rainbow Babies and Chil- dren’s Hospital, Cleveland, Ohio, is an outpatient clinic of a tertiary care hospital and serves the surrounding predominantly urban, low-income, African American pop- ulation. Medical providers include resident and attending physicians and nurse practitioners.

Study Intervention

The study intervention was treatment for 6 weeks with oral griseofulvin at a calculated dose of 20 to 25 mg/kg/ day, and topical selenium sulfide 2.5% shampoo twice weekly for all patients with a positive scalp culture for dermatophyte species. Shampoo therapy was included because earlier mycologic cure has been demonstrated with combination therapy compared to griseofulvin alone. 21,22 Families were counseled that combs, hats, and towels should not be shared because viable fungal spores can be cultured on inanimate objects. 20

Conduct of Study and Data Collection

Health providers identified patients with a clinical diagnosis of tinea capitis who were then approached by a research nurse from the Pediatric Pharmacology Research Unit (PPRU) for informed consent. Clinical evaluation and dermatophyte culture were performed at enrollment and at weeks 4, 6, and 8 (see appendix). Evaluation included assessment of symptoms, medical history, and adherence to treatment regimen (weeks 4 and 6). Symptoms recorded included (a) kerion, an inflammatory boggy mass on the scalp possibly with

crusting; (b) alopecia, defined as broken hairs or patches

of hair loss on the scalp; (c) scalp pruritis, defined as itch-

ing as reported by the patient or excessive scratching as noted by the guardian; (d) lymphadenopathy, defined as palpable occipital adenopathy; and (e) scaling, defined as flakiness of the scalp. Culture for dermatophyte spe- cies was obtained by vigorous toothbrush rubbing over the affected scalp area. Samples were placed into a Dermapak, transported to the Center for Medical Mycol- ogy of University Hospitals, and processed using standardized protocols. 23-25 Study medications were dispensed with written and oral instructions at enrollment. Patients with negative dermatophyte cultures were instructed to discontinue study medications and return to their primary physician. Patients with positive dermatophyte cultures continued medication for 6 weeks and were instructed to return at weeks 4, 6, and 8. The research nurse obtained 2 contact phone numbers and a current address, and saw the patient for each study visit. If a patient did not arrive, the family was phoned 3 times and a letter was sent to the home. Travel was fully reimbursed and study medication was provided free of charge by the PPRU.

Statistical Methods

A recruitment of 100 subjects was planned to have >95%

power to detect a significant association between alope- cia or occipital adenopathy and positive culture, using a 2-sided Fisher’s exact test (α = .05) and assuming the distribution of culture results and symptoms from prior studies. 12 It was expected that there would be a modest loss to follow-up of approximately 15% at each of the later time points. The demographic characteristics of the study popu- lation are described using frequencies and percents, with medians and ranges for nonparametric continuous variables. Predictive values of clinical symptoms. The presence or absence of clinical symptoms as described above was documented at each visit, and the corresponding culture


Clinical Pediatrics 49(3)

Table 1. Single Symptoms at Enrollment: Relationship to Positive Dermatophyte Culture


n (%)

Sensitivity, n (%)

Specificity, n (%)

PPV, n (%)

NPV, n (%)

Scaling Alopecia Pruritis Occipital lymphadenopathy Kerion


91/99 (92)

72/79 (91)

1/20 (5)

72/91 (79)

1/8 (13)

74/99 (73)

59/79 (75)

5/20 (25)

59/74 (80)

5/25 (20)

73/99 (74)

56/79 (71)

3/20 (15)

56/73 (77)

3/26 (12)

25/99 (25)

21/79 (27)

16/20 (80)

21/25 (84)

16/74 (22)

20/99 (20)

14/79 (18)

14/20 (70)

14/20 (70)

14/79 (18)

Abbreviations: PPV, positive predictive value; NPV, negative predictive value.


Table 2. Multiple Symptoms at Enrollment: Relationship to Positive Dermatophyte Culture




Sensitivity, n (%)

Specificity, n (%)

PPV, n (%)

NPV, n (%)

Any 1 symptom Any 2 symptoms Any 3 symptoms Any 4 symptoms


7/79 (9)

19/20 (95)

7/8 (88)

19/91 (21)


23/79 (29)

15/20 (75)

23/28 (82)

15/71 (19)


29/79 (37)

12/20 (60)

29/37 (78)

12/62 (19)


13/79 (17)

16/20 (80)

13/17 (77)

16/82 (20)

Abbreviations: PPV, positive predictive value; NPV, negative predictive value.

was classified as positive or negative. These were used to calculate sensitivity, specificity, positive predictive values, and negative predictive values for each symp- tom individually, for specific combinations of symptoms, and for nonspecific multiple symptoms at the baseline visit, and to establish clinical cure at subsequent visits. Clinical cure was defined as complete resolution of symptoms. Study population cure rates. We examined rates of myco- logic (negative dermatophyte culture) cure, clinical cure (absence of any symptoms), and complete cure (both mycologic and clinical cures) for the entire study cohort. Because not all patients were seen for each visit, we cal- culated (a) an observed rate based on the data for all patients who were either seen at the 8 week visit or who achieved negative culture (mycologic cure) or became free of study identified symptoms (clinical cure), (b) a hypothetical best rate of cure using the assumption that all patients lost to follow-up achieved negative culture or became free of symptoms, and (c) a hypothetical worst rate of cure using the assumption that all patients lost to follow-up did not achieve negative culture or become free of symptoms. Timing of cure. A subset of patients had complete myco- logic and symptomatic data. At each time point during treatment, the number and percent of observed myco- logic cures, clinical cures and complete cures from these patients were reported. McNemar’s test for signifi- cance of change was used to compare culture positivity between subsequent visits to test whether a signifi- cant improvement in cure rate continued throughout the study period.


A total of 99 patients were enrolled. The median age was 3.8 years (range 1.0-10.9 years), 48 (48%) were male and 98 (99%) were African American. At enrollment,


patients (79%) had a positive dermatophyte culture;


of these were lost to follow-up after the baseline visit

and another 19 missed one or more visits, resulting in

41 patients with complete data. The 79 patients with a

positive dermatophyte culture did not differ signifi- cantly with respect to age or gender from the 20 patients with a negative culture at enrollment. The 41 patients with complete data did not differ significantly with regard to age or gender from the 38 patients who had one or more missed visits. We calculated the frequency, sensitivity, specificity, and positive and negative predictive values of individual symptoms (Table 1) and of combinations of 2 or more symptoms (Table 2) for a positive dermatophyte culture prior to treatment. We examined rates of mycological, clinical, and com- plete cure for the entire study cohort. In all, 26 patients neither achieved a negative culture nor had data for week 8, and thus the observed rate of mycologic cure was 47/53 (89%). The hypothetical best possible rate of myco- logic cure would have been 73/79 (92%) and the hypothetical worst possible rate would have been 47/79 (60%). The observed rate of any clinical cure was 29/53 (55%). The hypothetical best rate of clinical cure was 61/79 (77%) and the hypothetical worst rate was 29/79 (37%). Finally, the observed rate of complete cure, defined as both mycologic and clinical cure, was 26/53 (49%),

Lorch Dauk et al.


40 34 35 * 31 30 25 22 19 20 * 18 * 15 13
week 4
week 6
Timing of visit
week 8
Number cured

Figure 1. Timing of cure.

*P < .05 compared to the previous visit.

with a hypothetical best rate of 52/79 (66%), and a hypo-

thetical worst rate of 26/79 (33%). Three patients achieved

a negative culture (mycologic cure) but subsequently had

a positive culture at week 8, and 5 patients achieved clini- cal cure but had symptoms noted again at week 8. We then examined the timing of mycological, clini- cal, and complete cure among the 41 patients for whom complete visit data were available, as presented in Figure 1. There was a significant increase in the rates of culture negativity (P = .007) and clinical cure (P = .02) from weeks 4 to 6, but after treatment was discontinued the further increases were not statistically significant (P = .26 and P = .11, respectively). Finally, the rate of complete cure increased significantly both from weeks 4 to 6 (P = .03) and from weeks 6 to 8 (P = .03).


Tinea capitis is a common condition, and parents and child care providers are eager to obtain treatment for

possibly infected children due to discomfort and risk of contagion. Among 99 children aged 1 to 12 years pre- senting with symptoms suggestive of tinea capitis, we found positive dermatophyte cultures among 79 (79%). The positive predictive value of any one symptom for

a positive culture was as good as any combination or

number of symptoms. We found that a “real world” treatment regimen of griseofulvin at 20 to 25 mg/kg/day for 6 weeks combined with twice weekly topical sele- nium sulfide 2.5% shampoo was moderately successful, yielding an observed mycologic cure rate of 89%, clini- cal cure rate of 55%, and complete cure rate of 49%.

Mycologic cure appeared to precede clinical cure, and

the rate of complete cure continued to increase 2 weeks after treatment ended.

The positive predictive values of individual symptoms for a positive dermatophyte culture that we report are in agreement with the work of others (alopecia [84% vs our

80%], scaling [71% vs our 79%], pruritis [75% vs our

77%], and adenopathy [94% vs our 84%]). 12 Hubbard 12

found that a positive culture was significantly associated

with the number of signs or symptoms: all children with

4 symptoms (scaling, alopecia, itching, and adenopathy)

had positive dermatophyte cultures, and none of 6 children with only one presenting symptom had a positive cul- ture. In comparison, we found that 1 symptom was as predictive as any number of symptoms, with nearly identical 95% confidence intervals for positive predic- tive values (positive predictive value for 1 symptom 88% [1.0-0.65]; 2 symptoms 82% [0.96-0.68]; 3 symp- toms 78% [0.92-0.65]; 4 symptoms 77% [0.97-0.56]). This discrepancy between studies may be explained by 2 factors. First, Hubbard’s study defined adenopathy more broadly and reported a higher prevalence (90% vs 25%). Second, we included patients with kerion, atopic dermatitis, and other skin conditions who were excluded from the Hubbard study. The relatively lower positive

predictive value (70%) of kerion is likely due to the difficulty of culture in the presence of extensive inflam- matory reaction. Atopic dermatitis (eczema) is common and affects 10% to 20% of school-age children; it is pos- sible that some patients with atopic dermatitis and only

1 symptom, but a positive dermatophyte culture, were

actually asymptomatic for tinea capitis and symptomatic for atopic dermatitis and were thus misclassified. This is a “real world” dilemma, which is not readily resolved. The rates of mycologic, clinical, and complete cure reported here are within the ranges reported for treatment of tinea capitis with both grisefulvin and terbinafine. Rates of mycologic cure after treatment with griseofulvin range from 62% to 96% and with ter- binafine range from 61% to 86%: differences may be due to secular trends in dermatophyte resistance, dose and duration of treatment, use of adjunctive topical ther-

apy and timing of testing. 11,14,15,26,27 It is possible that the complete cure rates reported here would continue to improve with a longer follow-up. Few studies have examined outcomes with griseofulvin treatment at doses of 20 to 25 mg/kg/day. In a recently published multisite study, Elewski et al 14 reported that complete cure and mycological cure alone were significantly better with a

6 week regimen of terbinafine than griseofulvin, although clinical cure alone was not significantly different between the 2 regimens. A secondary analysis showed no effect of dose on treatment outcome, but only 13.3% (49/434) of study patients had received >20 mg/kg/day


Clinical Pediatrics 49(3)

of griseofulvin, and higher doses of griseofulvin as provided in this study might be equivalent or superior to terbinafine. The rate of positive dermatophyte culture among chil- dren with symptoms of tinea capitis in this study is similar to that of other studies. 12,14,28 Although culture is typi- cally considered the “gold standard” for diagnosis of tinea capitis, in fact the reported sensitivity of fungal culture for dermatophytes is likely very close to the rate documented in this study. Elewski et al 14 studied 1,549 children with symptoms of tinea capitis who had positive KOH microscopy of hair samples: 17% had simul- taneous negative dermatophyte cultures, yielding a calculated culture sensitivity of 83% (cf. 79% in this study). We speculate that the 20 children in our study with symptoms of tinea capitis but with negative cultures may have had falsely negative cultures. In support of this working hypothesis, we found no significant dif- ference in the prevalence of each individual symptom among children with negative cultures as compared to those with positive cultures (alopecia 75% vs 75%, respectively, P = 1.0; itching 85% vs 71%, P = .26; scal- ing 95% vs 91%, P = 1.0; kerion 30% vs 18%, P = 0.23; adenopathy 20% vs 27%, P = .77). Also in support, 6 (30%) of the 20 children with negative cultures had a kerion, the inflammatory boggy scalp mass that is gener- ally considered pathognomonic for tinea capitis disease. If this working hypothesis is correct, then the calculated positive predictive values of clinical symptoms reported here, although in agreement with those reported from other studies, actually represent an estimate of the posi- tive culture rate. 12 If this is so, then the true positive predictive values of symptoms for tinea capitis disease would much be higher. Strengths of this study include the use of a large cohort with few exclusionary criteria, culturing of the scalp to verify diagnosis, longitudinal follow-up, and a “real world” medication regimen. Also, we included chil- dren with previously diagnosed skin conditions including atopic dermatitis, and children with kerion, so results can be generalized to a broader population. Weaknesses of this study include a high lost to follow- up rate and the possibility of poor compliance with medications, which would tend to skew results toward underestimating treatment effectiveness. Overall, 24 of 79 patients with positive cultures (30%) did not return at week 4, and 33 (42%) did not return (each) at weeks 6 and 8. We speculate but cannot prove that the patients who were symptomatic were the ones most likely to return. Medication compliance was not objectively measured, and families often “forgot” to bring their medication bottle back at each visit. Compliance with a daily oral medication for 6 weeks may be low, and this would

decrease cure rates. It is challenging to conduct longitudi- nal studies in urban low-income populations; a financial incentive and home visiting might improve compliance in future studies. An additional weakness of the study is that we did not follow or treat the 20 children with symptoms of tinea capitis and initial negative dermatophyte cultures. Although we hypothesize that these children had true dis- ease and a false negative culture, it would have strengthened our study conclusions to document clinical improvement of these children with treatment. Two of the 3 patients whose cultures reverted from negative to positive after treatment ended had no associ- ated symptoms and may have become carriers. Several studies have confirmed the existence of a carrier state, with rates ranging from 5% in populations at low risk to 44% among urban children in a day care center. 1-3,7 The relationship of the carrier state (positive culture without symptoms) to disease (positive culture with symptoms) is complex, with evidence suggesting that children who harbor the same fungal strain over a period of time are more likely to become symptomatic than those who acquire and shed multiple strains. 7 Abdel-Rahman et al 7 reported from a large urban day care center that the sensitivity and specificity of a positive dermatophyte culture for symptoms of tinea capitis (scaling and/or alopecia plus one or more “clinical indicators”) were 66.1% and 66.5%, respectively. Although terbinafine has been approved for treatment of tinea capitis in children, many clinicians continue to use griseofulvin because it is less expensive, has a good safety record, and is a formulary choice for many insurance plans. 25 Our data support treatment with 20 to 25 mg/kg/day of oral griseofulvin augmented by sham- pooing with 2.5% selenium sulfide shampoo for a minimum of 6 weeks as a moderately successful treat- ment for children with symptoms of tinea capitis and concurrent positive dermatophyte culture. We also present evidence that in a high-risk popula- tion it is reasonable for clinicians to make the diagnosis of tinea capitis using one or more cardinal symptoms without obtaining culture. Additional study is needed, but given the imperfect sensitivity of fungal culture, it appears that symptoms of tinea capitis may in fact be more reliable as predictors of disease than culture. Fungal culture of the scalp for diagnosis of tinea capitis may cost $60 to $100 and take up to 2 weeks, which increases the cost of care, delays treatment, and likely increases disease spread. If there is diagnostic confu- sion or unexplained recurrence, culture may be an appropriate diagnostic tool. However, use of clinical criteria for initial diagnosis in an urban low-income predominantly African American population is sup- ported by this study.

Lorch Dauk et al.


Appendix Study Visit Protocol

Visit 1—Baseline (Day 1)


Written informed consent.


Conformance with entry criteria.


Significant medical history including date of birth, past/current medical history, past/ current medications, duration and type of past/present infection(s), and household information.


Samples for dermatophte culture to confirm the clinical diagnosis.


Physical exam for stigmata of tinea corporis, eczema, and psoriasis.


Assessment for clinical criteria as listed above. Pruritis of scalp will be verbally reported by subject and parent/guardian.


Weight will be obtained to calculate dosage of griseofulvin.


Concomitant medications will be recorded.


Study medication and shampoo will be dis- pensed to subject.


Investigators will instruct subjects and house- hold members on proper hygiene to prevent spread of infection.


Patient and guardian will be informed by mail that if initial culture is negative they will be referred back to their primary care provider and will not continue in the study.

Visit 2—Week 4



2. Samples for dermatophyte culture.

3. Study medication and shampoo dispensed.

4. Exam for clinical criteria as listed above. Pruri- tis of scalp will be verbally reported by subject and parent/guardian.

5. Adverse events recorded.

6. Verbal reporting by parent/guardian regard- ing compliance with treatment regimen.

Visit 3—Week 6

1. Samples for dermatophyte culture.

2. Study medication and shampoo treatment completed.

3. Exam for clinical criteria as listed above. Pruri- tis of scalp will be verbally reported by subject and parent/guardian.

4. Adverse events recorded.

5. Verbal reporting by parent/guarding regard- ing compliance with treatment regimen.

Visit 4—Week 8

1. Samples for dermatophyte culture.

2. Exam for clinical criteria as listed above. Pruri- tis of scalp will be verbally reported by subject and parent/guardian.

3. Completion of Study Subject Summary.

4. Adverse events recorded.


We thank Nancy Isham and Dr M. Ghannoum, Director, both of the Center for Medical Mycology, University Hospitals, Cleveland. Thanks to research nurse Roberta Ksenisch, RN, and research coordinator Bonnie Roso- lowski, RRT, CCRC, of the Pediatric Pharmacology Research Unit (PPRU). We acknowledge the support of the PPRU via the Pediatric Pharmacology Research Unit Grant from the National Institute of Child Health and Human Development (HD 31323-12). The project would not have been possible without PPRU support.


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