The gold standard for diagnosing dermatophytosis is the use of direct microscopic examination together with fungal culture.¹ However, in the last 2 decades, molecular techniques that currently are available worldwide have improved the diagnosis procedure.^2,3 In the practice of dermatology, potassium hydroxide (KOH) testing is a commonly used method for the diagnosis of superficial fungal infections.⁴ The sensitivity and specificity of KOH testing in patients with tinea pedis have been reported as 73.3% and 42.5%, respectively.⁵ Repetition of this test after an initial negative test result is recommended if the clinical picture strongly suggests a fungal infection.^6,7 Alternatively, several repetitions of direct microscopic examinations also have been proposed for detecting other microorganisms. For example, 3 negative sputum smears traditionally are recommended to exclude a diagnosis of pulmonary tuberculosis.⁸ However, after numerous investigations in various regions of the world, the World Health Organization reduced the recommended number of these specimens from 3 to 2 in 2007.⁹

The literature suggests that successive mycological tests, both with direct microscopy and fungal cultures, improve the diagnosis of onychomycosis.^1,10,11 Therefore, if such investigations are increased in number, recommendations for successive mycological tests may be more reliable. In the current study, we aimed to investigate the value of successive KOH testing in the management of patients with clinically suspected tinea pedis.

Methods

Patients and Clinical Evaluation
One hundred thirty-five consecutive patients (63 male; 72 female) with clinical symptoms suggestive of intertriginous, vesiculobullous, and/or moccasin-type tinea pedis were enrolled in this prospective study. The mean age (SD) of patients was 45.9 (14.7) years (range, 11–77 years). Almost exclusively, the clinical symptoms suggestive of tinea pedis were desquamation or maceration in the toe webs, blistering lesions on the soles, and diffuse or patchy scaling or keratosis on the soles. A single dermatologist (B.F.K.) clinically evaluated the patients and found only 1 region showing different patterns suggestive of tinea pedis in 72 patients, 2 regions in 61 patients, and 3 regions in 2 patients. Therefore, 200 lesions from the 135 patients were chosen for the KOH test. The dermatologist recorded her level of suspicion for a fungal infection as low or high for each lesion, depending on the absence or presence of signs (eg, unilateral involvement, a well-defined border). None of the patients had used topical or systemic antifungal therapy for at least 1 month prior to the study.¹²

Clinical Sampling and Direct Microscopic Examination
The dermatologist took 3 samples of skin scrapings from each of the 200 lesions. All 3 samples from a given lesion were obtained from sites with the same clinical symptoms in a single session. Special attention was paid to samples from the active advancing borders of the lesions and the roofs of blisters if they were present.¹³ Upon completion of every 15 samples from every 5 lesions, the dermatologist randomized the order of the samples (https://www.random.org/). She then gave the samples, without the identities of the patients or any clinical information, to an experienced laboratory technician for direct microscopic examination. The technician prepared and examined the samples as described elsewhere^5,7,14 and recorded the results as positive if hyphal elements were present or negative if they were not. The study was reviewed and approved by the Çukurova University Faculty of Medicine Ethics Committee (Adana, Turkey). Informed consent was obtained from each patient or from his/her guardian(s) prior to initiating the study.

Statistical Analysis
Statistical analysis was conducted using the χ² test in the SPSS software version 20.0. McNemar test was used for analysis of the paired data.

Results

Among the 135 patients, lesions were suggestive of the intertriginous type of tinea pedis in 24 patients, moccasin type in 50 patients, and both intertriginous and moccasin type in 58 patients. Among the remaining 3 patients, 1 had lesions suggestive of the vesiculobullous type, and another patient had both the vesiculobullous and intertriginous types; the last patient demonstrated lesions that were inconsistent with any of these 3 subtypes of tinea pedis, and a well-defined eczematous plaque was observed on the dorsal surface of the patient’s left foot.

Among the 200 lesions from which skin scrapings were taken for KOH testing, 83 were in the toe webs, 110 were on the soles, and 7 were on the dorsal surfaces of the feet. Of these 7 dorsal lesions, 6 were extensions from lesions on the toe webs or soles and 1 was inconsistent with the 3 subtypes of tinea pedis. Among the 200 lesions, the main clinical symptom was maceration in 38 lesions, desquamation or scaling in 132 lesions, keratosis in 28 lesions, and blistering in 2 lesions. The dermatologist recorded the level of suspicion for tinea pedis as low in 68 lesions and high in 132.

According to the order in which the dermatologist took the 3 samples from each lesion, the KOH test was positive in 95 of the first set of 200 samples, 94 of the second set, and 86 of the third set; however, from the second set, the incremental yield (ie, the number of lesions in which the first KOH test was negative and the second was positive) was 10. The number of lesions in which the first and the second tests were negative and the third was positive was only 4. Therefore, the number of lesions with a positive KOH test was significantly increased from 95 to 105 by performing the second KOH test (P=.002). This number again increased from 105 to 109 when a third test was performed; however, this increase was not statistically significant (P=.125)(Table 1).

According to an evaluation that was not stratified by the dermatologist’s order of sampling, 72 lesions (36.0%) showed KOH test positivity in all 3 samples, 22 (11.0%) were positive in 2 samples, 15 (7.5%) were positive in only 1 sample, and 91 (45.5%) were positive in none of the samples (Table 2). When the data were subdivided based on the sites of the lesions, the toe web lesions (n=83) showed rates of 41.0%, 9.6%, and 4.8% for 3, 2, and 1 positive KOH tests, respectively. For the sole lesions (n=110), the rates were somewhat different at 31.8%, 11.8%, and 10.0%, respectively, but the difference was not statistically significant (P=.395).

For the subgroups based on the main clinical symptoms, the percentage of lesions having at least 1 positive KOH test from the 3 samples was 35.7% for the keratotic lesions (n=28). This rate was lower than macerated lesions (n=38) and desquamating or scaling lesions (n=132), which were 52.6% and 59.1%, respectively (Table 2). On the other hand, the percentage of lesions that produced only 1 or 2 positive KOH tests from the 3 samples was 25.0% for the keratotic lesions, which was higher than the rates for the macerated lesions and the desquamating or scaling lesions (13.1% and 18.9%, respectively). In particular, the difference between the keratotic lesions and the desquamating or scaling lesions in the distribution of the rates of 0, 1, 2, and 3 positive KOH tests was statistically significant (P=.019). The macerated, desquamating or scaling, keratotic, and blistering lesions are presented in the Figure.

Comment

In the current study, we aimed to investigate if successive KOH tests provide an incremental diagnostic yield in the management of patients with clinically suspected tinea pedis and if these results differ among the subgroups of patients. Both in the evaluation taking into account the order of sampling and in the evaluation disregarding this order, we found that the second sample was necessary for all subgroups, and even the third sample was necessary for patients with keratotic lesions. The main limitation of the study was that we lacked a gold-standard technique (eg, a molecular-based technique); therefore, we are unable to comment on the false-negative and false-positive results of the successive KOH testing.

Summerbell et al¹¹ found in their study that in initial specimens of toenails with apparent lesions taken from 473 patients, the KOH test was 73.8% sensitive for dermatophytes, and this rate was only somewhat higher for cultures (74.6%). Arabatzis et al² investigated 92 skin, nail, and hair specimens from 67 patients with suspected dermatophytosis and found that the KOH test was superior to culture for the detection of dermatophytes (43% vs 33%). Moreover and more importantly, they noted that a real-time polymerase chain reaction (PCR) assay yielded a higher detection rate (51%).² In another study, Wisselink et al³ examined 1437 clinical samples and demonstrated a great increase in the detection of dermatophytes using a real-time PCR assay (48.5%) compared to culture (26.9%). However, PCR may not reflect active disease and could lead to false-positive results.^2,3 Therefore, the aforementioned weakness of our study will be overcome in further studies investigating the benefit of successive KOH testing compared to a molecular-based assay, such as the real-time PCR assay.

In this study, repeating the KOH test provided better results for achieving the diagnosis of tinea pedis in a large number of samples from clinically suspected lesions. Additionally, the distribution of 3, 2, or 1 positive results on the 3 KOH tests was different among the subgroups of lesions. Overall, positivity was less frequent in the keratotic lesions compared to the macerated or desquamating or scaling lesions. Moreover, positivity on all 3 tests also was less frequent in the keratotic lesions. Inversely, the frequency of samples with only 1 or 2 positive results was higher in this subgroup. The necessity for the second, even the third, tests was greater in this subgroup.

Our findings were consistent with the results of the studies performed with successive mycological tests on the nail specimens. Meireles et al¹ repeated 156 mycological nail tests 3 times and found the rate of positivity in the first test to be 19.9%. When the results of the first and second tests were combined, this rate increased to 28.2%, and when the results of all 3 tests were combined, it increased to 37.8%.¹ Gupta¹⁰ demonstrated that even a fourth culture provided an incremental diagnostic yield in the diagnosis of onychomycosis, yet 4 cultures may not be clinically practical. Furthermore, periodic acid–Schiff staining is a more effective measure of positivity in onychomycosis.¹⁵

Although the overall rate of positivity on the 3 tests in our study was unsurprisingly higher in lesions rated highly suspicious for a fungal infection, the rate of only 1 or 2 positive tests was surprisingly somewhat higher in low-suspicion lesions, which suggested that repeating the KOH test would be beneficial, even if the clinical suspicion for tinea pedis was low. The novel contribution of this study includes the finding that mycological information was markedly improved in highly suspicious tinea pedis lesions regardless of the infection site (Table 1) by using 3 successive KOH tests; the percentage of lesions with 1, 2, or 3 positive KOH tests was 5.3%, 12.1%, and 47.0%, respectively (Table 2). A single physician from a single geographical location introduces a limitation to the study for a variety of reasons, including bias in the cases chosen and possible overrepresentation of the causative organism due to region-specific incidence. It is unknown how different causative organisms affect KOH results. The lack of fungal culture results limits the value of this information.

Conclusion

In this study, we investigated the benefit of successive KOH testing in the laboratory diagnosis of tinea pedis and found that the use of second samples in particular provided a substantial increase in diagnostic yield. In other words, the utilization of successive KOH testing remarkably improved the diagnosis of tinea pedis. Therefore, we suggest that at least 2 samples of skin scrapings should be taken for the diagnosis of tinea pedis and that the number of samples should be at least 3 for keratotic lesions. However, further study by using a gold-standard method such as a molecular-based assay as well as taking the samples in daily or weekly intervals is recommended to achieve a more reliable result.

Acknowledgment

The authors would like to thank Gökçen Şahin (Adana, Turkey) for providing technical support in direct microscopic examination.

The gold standard for diagnosing dermatophytosis is the use of direct microscopic examination together with fungal culture.¹ However, in the last 2 decades, molecular techniques that currently are available worldwide have improved the diagnosis procedure.^2,3 In the practice of dermatology, potassium hydroxide (KOH) testing is a commonly used method for the diagnosis of superficial fungal infections.⁴ The sensitivity and specificity of KOH testing in patients with tinea pedis have been reported as 73.3% and 42.5%, respectively.⁵ Repetition of this test after an initial negative test result is recommended if the clinical picture strongly suggests a fungal infection.^6,7 Alternatively, several repetitions of direct microscopic examinations also have been proposed for detecting other microorganisms. For example, 3 negative sputum smears traditionally are recommended to exclude a diagnosis of pulmonary tuberculosis.⁸ However, after numerous investigations in various regions of the world, the World Health Organization reduced the recommended number of these specimens from 3 to 2 in 2007.⁹

The literature suggests that successive mycological tests, both with direct microscopy and fungal cultures, improve the diagnosis of onychomycosis.^1,10,11 Therefore, if such investigations are increased in number, recommendations for successive mycological tests may be more reliable. In the current study, we aimed to investigate the value of successive KOH testing in the management of patients with clinically suspected tinea pedis.

Methods

Patients and Clinical Evaluation
One hundred thirty-five consecutive patients (63 male; 72 female) with clinical symptoms suggestive of intertriginous, vesiculobullous, and/or moccasin-type tinea pedis were enrolled in this prospective study. The mean age (SD) of patients was 45.9 (14.7) years (range, 11–77 years). Almost exclusively, the clinical symptoms suggestive of tinea pedis were desquamation or maceration in the toe webs, blistering lesions on the soles, and diffuse or patchy scaling or keratosis on the soles. A single dermatologist (B.F.K.) clinically evaluated the patients and found only 1 region showing different patterns suggestive of tinea pedis in 72 patients, 2 regions in 61 patients, and 3 regions in 2 patients. Therefore, 200 lesions from the 135 patients were chosen for the KOH test. The dermatologist recorded her level of suspicion for a fungal infection as low or high for each lesion, depending on the absence or presence of signs (eg, unilateral involvement, a well-defined border). None of the patients had used topical or systemic antifungal therapy for at least 1 month prior to the study.¹²

Clinical Sampling and Direct Microscopic Examination
The dermatologist took 3 samples of skin scrapings from each of the 200 lesions. All 3 samples from a given lesion were obtained from sites with the same clinical symptoms in a single session. Special attention was paid to samples from the active advancing borders of the lesions and the roofs of blisters if they were present.¹³ Upon completion of every 15 samples from every 5 lesions, the dermatologist randomized the order of the samples (https://www.random.org/). She then gave the samples, without the identities of the patients or any clinical information, to an experienced laboratory technician for direct microscopic examination. The technician prepared and examined the samples as described elsewhere^5,7,14 and recorded the results as positive if hyphal elements were present or negative if they were not. The study was reviewed and approved by the Çukurova University Faculty of Medicine Ethics Committee (Adana, Turkey). Informed consent was obtained from each patient or from his/her guardian(s) prior to initiating the study.

Statistical Analysis
Statistical analysis was conducted using the χ² test in the SPSS software version 20.0. McNemar test was used for analysis of the paired data.

Results

Among the 135 patients, lesions were suggestive of the intertriginous type of tinea pedis in 24 patients, moccasin type in 50 patients, and both intertriginous and moccasin type in 58 patients. Among the remaining 3 patients, 1 had lesions suggestive of the vesiculobullous type, and another patient had both the vesiculobullous and intertriginous types; the last patient demonstrated lesions that were inconsistent with any of these 3 subtypes of tinea pedis, and a well-defined eczematous plaque was observed on the dorsal surface of the patient’s left foot.

Among the 200 lesions from which skin scrapings were taken for KOH testing, 83 were in the toe webs, 110 were on the soles, and 7 were on the dorsal surfaces of the feet. Of these 7 dorsal lesions, 6 were extensions from lesions on the toe webs or soles and 1 was inconsistent with the 3 subtypes of tinea pedis. Among the 200 lesions, the main clinical symptom was maceration in 38 lesions, desquamation or scaling in 132 lesions, keratosis in 28 lesions, and blistering in 2 lesions. The dermatologist recorded the level of suspicion for tinea pedis as low in 68 lesions and high in 132.

According to the order in which the dermatologist took the 3 samples from each lesion, the KOH test was positive in 95 of the first set of 200 samples, 94 of the second set, and 86 of the third set; however, from the second set, the incremental yield (ie, the number of lesions in which the first KOH test was negative and the second was positive) was 10. The number of lesions in which the first and the second tests were negative and the third was positive was only 4. Therefore, the number of lesions with a positive KOH test was significantly increased from 95 to 105 by performing the second KOH test (P=.002). This number again increased from 105 to 109 when a third test was performed; however, this increase was not statistically significant (P=.125)(Table 1).

According to an evaluation that was not stratified by the dermatologist’s order of sampling, 72 lesions (36.0%) showed KOH test positivity in all 3 samples, 22 (11.0%) were positive in 2 samples, 15 (7.5%) were positive in only 1 sample, and 91 (45.5%) were positive in none of the samples (Table 2). When the data were subdivided based on the sites of the lesions, the toe web lesions (n=83) showed rates of 41.0%, 9.6%, and 4.8% for 3, 2, and 1 positive KOH tests, respectively. For the sole lesions (n=110), the rates were somewhat different at 31.8%, 11.8%, and 10.0%, respectively, but the difference was not statistically significant (P=.395).

For the subgroups based on the main clinical symptoms, the percentage of lesions having at least 1 positive KOH test from the 3 samples was 35.7% for the keratotic lesions (n=28). This rate was lower than macerated lesions (n=38) and desquamating or scaling lesions (n=132), which were 52.6% and 59.1%, respectively (Table 2). On the other hand, the percentage of lesions that produced only 1 or 2 positive KOH tests from the 3 samples was 25.0% for the keratotic lesions, which was higher than the rates for the macerated lesions and the desquamating or scaling lesions (13.1% and 18.9%, respectively). In particular, the difference between the keratotic lesions and the desquamating or scaling lesions in the distribution of the rates of 0, 1, 2, and 3 positive KOH tests was statistically significant (P=.019). The macerated, desquamating or scaling, keratotic, and blistering lesions are presented in the Figure.

Comment

In the current study, we aimed to investigate if successive KOH tests provide an incremental diagnostic yield in the management of patients with clinically suspected tinea pedis and if these results differ among the subgroups of patients. Both in the evaluation taking into account the order of sampling and in the evaluation disregarding this order, we found that the second sample was necessary for all subgroups, and even the third sample was necessary for patients with keratotic lesions. The main limitation of the study was that we lacked a gold-standard technique (eg, a molecular-based technique); therefore, we are unable to comment on the false-negative and false-positive results of the successive KOH testing.

Summerbell et al¹¹ found in their study that in initial specimens of toenails with apparent lesions taken from 473 patients, the KOH test was 73.8% sensitive for dermatophytes, and this rate was only somewhat higher for cultures (74.6%). Arabatzis et al² investigated 92 skin, nail, and hair specimens from 67 patients with suspected dermatophytosis and found that the KOH test was superior to culture for the detection of dermatophytes (43% vs 33%). Moreover and more importantly, they noted that a real-time polymerase chain reaction (PCR) assay yielded a higher detection rate (51%).² In another study, Wisselink et al³ examined 1437 clinical samples and demonstrated a great increase in the detection of dermatophytes using a real-time PCR assay (48.5%) compared to culture (26.9%). However, PCR may not reflect active disease and could lead to false-positive results.^2,3 Therefore, the aforementioned weakness of our study will be overcome in further studies investigating the benefit of successive KOH testing compared to a molecular-based assay, such as the real-time PCR assay.

In this study, repeating the KOH test provided better results for achieving the diagnosis of tinea pedis in a large number of samples from clinically suspected lesions. Additionally, the distribution of 3, 2, or 1 positive results on the 3 KOH tests was different among the subgroups of lesions. Overall, positivity was less frequent in the keratotic lesions compared to the macerated or desquamating or scaling lesions. Moreover, positivity on all 3 tests also was less frequent in the keratotic lesions. Inversely, the frequency of samples with only 1 or 2 positive results was higher in this subgroup. The necessity for the second, even the third, tests was greater in this subgroup.

Our findings were consistent with the results of the studies performed with successive mycological tests on the nail specimens. Meireles et al¹ repeated 156 mycological nail tests 3 times and found the rate of positivity in the first test to be 19.9%. When the results of the first and second tests were combined, this rate increased to 28.2%, and when the results of all 3 tests were combined, it increased to 37.8%.¹ Gupta¹⁰ demonstrated that even a fourth culture provided an incremental diagnostic yield in the diagnosis of onychomycosis, yet 4 cultures may not be clinically practical. Furthermore, periodic acid–Schiff staining is a more effective measure of positivity in onychomycosis.¹⁵

Although the overall rate of positivity on the 3 tests in our study was unsurprisingly higher in lesions rated highly suspicious for a fungal infection, the rate of only 1 or 2 positive tests was surprisingly somewhat higher in low-suspicion lesions, which suggested that repeating the KOH test would be beneficial, even if the clinical suspicion for tinea pedis was low. The novel contribution of this study includes the finding that mycological information was markedly improved in highly suspicious tinea pedis lesions regardless of the infection site (Table 1) by using 3 successive KOH tests; the percentage of lesions with 1, 2, or 3 positive KOH tests was 5.3%, 12.1%, and 47.0%, respectively (Table 2). A single physician from a single geographical location introduces a limitation to the study for a variety of reasons, including bias in the cases chosen and possible overrepresentation of the causative organism due to region-specific incidence. It is unknown how different causative organisms affect KOH results. The lack of fungal culture results limits the value of this information.

Conclusion

In this study, we investigated the benefit of successive KOH testing in the laboratory diagnosis of tinea pedis and found that the use of second samples in particular provided a substantial increase in diagnostic yield. In other words, the utilization of successive KOH testing remarkably improved the diagnosis of tinea pedis. Therefore, we suggest that at least 2 samples of skin scrapings should be taken for the diagnosis of tinea pedis and that the number of samples should be at least 3 for keratotic lesions. However, further study by using a gold-standard method such as a molecular-based assay as well as taking the samples in daily or weekly intervals is recommended to achieve a more reliable result.

Acknowledgment

The authors would like to thank Gökçen Şahin (Adana, Turkey) for providing technical support in direct microscopic examination.

The gold standard for diagnosing dermatophytosis is the use of direct microscopic examination together with fungal culture.¹ However, in the last 2 decades, molecular techniques that currently are available worldwide have improved the diagnosis procedure.^2,3 In the practice of dermatology, potassium hydroxide (KOH) testing is a commonly used method for the diagnosis of superficial fungal infections.⁴ The sensitivity and specificity of KOH testing in patients with tinea pedis have been reported as 73.3% and 42.5%, respectively.⁵ Repetition of this test after an initial negative test result is recommended if the clinical picture strongly suggests a fungal infection.^6,7 Alternatively, several repetitions of direct microscopic examinations also have been proposed for detecting other microorganisms. For example, 3 negative sputum smears traditionally are recommended to exclude a diagnosis of pulmonary tuberculosis.⁸ However, after numerous investigations in various regions of the world, the World Health Organization reduced the recommended number of these specimens from 3 to 2 in 2007.⁹

The literature suggests that successive mycological tests, both with direct microscopy and fungal cultures, improve the diagnosis of onychomycosis.^1,10,11 Therefore, if such investigations are increased in number, recommendations for successive mycological tests may be more reliable. In the current study, we aimed to investigate the value of successive KOH testing in the management of patients with clinically suspected tinea pedis.

Methods

Patients and Clinical Evaluation
One hundred thirty-five consecutive patients (63 male; 72 female) with clinical symptoms suggestive of intertriginous, vesiculobullous, and/or moccasin-type tinea pedis were enrolled in this prospective study. The mean age (SD) of patients was 45.9 (14.7) years (range, 11–77 years). Almost exclusively, the clinical symptoms suggestive of tinea pedis were desquamation or maceration in the toe webs, blistering lesions on the soles, and diffuse or patchy scaling or keratosis on the soles. A single dermatologist (B.F.K.) clinically evaluated the patients and found only 1 region showing different patterns suggestive of tinea pedis in 72 patients, 2 regions in 61 patients, and 3 regions in 2 patients. Therefore, 200 lesions from the 135 patients were chosen for the KOH test. The dermatologist recorded her level of suspicion for a fungal infection as low or high for each lesion, depending on the absence or presence of signs (eg, unilateral involvement, a well-defined border). None of the patients had used topical or systemic antifungal therapy for at least 1 month prior to the study.¹²

Clinical Sampling and Direct Microscopic Examination
The dermatologist took 3 samples of skin scrapings from each of the 200 lesions. All 3 samples from a given lesion were obtained from sites with the same clinical symptoms in a single session. Special attention was paid to samples from the active advancing borders of the lesions and the roofs of blisters if they were present.¹³ Upon completion of every 15 samples from every 5 lesions, the dermatologist randomized the order of the samples (https://www.random.org/). She then gave the samples, without the identities of the patients or any clinical information, to an experienced laboratory technician for direct microscopic examination. The technician prepared and examined the samples as described elsewhere^5,7,14 and recorded the results as positive if hyphal elements were present or negative if they were not. The study was reviewed and approved by the Çukurova University Faculty of Medicine Ethics Committee (Adana, Turkey). Informed consent was obtained from each patient or from his/her guardian(s) prior to initiating the study.

Statistical Analysis
Statistical analysis was conducted using the χ² test in the SPSS software version 20.0. McNemar test was used for analysis of the paired data.

Results

Among the 135 patients, lesions were suggestive of the intertriginous type of tinea pedis in 24 patients, moccasin type in 50 patients, and both intertriginous and moccasin type in 58 patients. Among the remaining 3 patients, 1 had lesions suggestive of the vesiculobullous type, and another patient had both the vesiculobullous and intertriginous types; the last patient demonstrated lesions that were inconsistent with any of these 3 subtypes of tinea pedis, and a well-defined eczematous plaque was observed on the dorsal surface of the patient’s left foot.

Among the 200 lesions from which skin scrapings were taken for KOH testing, 83 were in the toe webs, 110 were on the soles, and 7 were on the dorsal surfaces of the feet. Of these 7 dorsal lesions, 6 were extensions from lesions on the toe webs or soles and 1 was inconsistent with the 3 subtypes of tinea pedis. Among the 200 lesions, the main clinical symptom was maceration in 38 lesions, desquamation or scaling in 132 lesions, keratosis in 28 lesions, and blistering in 2 lesions. The dermatologist recorded the level of suspicion for tinea pedis as low in 68 lesions and high in 132.

According to the order in which the dermatologist took the 3 samples from each lesion, the KOH test was positive in 95 of the first set of 200 samples, 94 of the second set, and 86 of the third set; however, from the second set, the incremental yield (ie, the number of lesions in which the first KOH test was negative and the second was positive) was 10. The number of lesions in which the first and the second tests were negative and the third was positive was only 4. Therefore, the number of lesions with a positive KOH test was significantly increased from 95 to 105 by performing the second KOH test (P=.002). This number again increased from 105 to 109 when a third test was performed; however, this increase was not statistically significant (P=.125)(Table 1).

According to an evaluation that was not stratified by the dermatologist’s order of sampling, 72 lesions (36.0%) showed KOH test positivity in all 3 samples, 22 (11.0%) were positive in 2 samples, 15 (7.5%) were positive in only 1 sample, and 91 (45.5%) were positive in none of the samples (Table 2). When the data were subdivided based on the sites of the lesions, the toe web lesions (n=83) showed rates of 41.0%, 9.6%, and 4.8% for 3, 2, and 1 positive KOH tests, respectively. For the sole lesions (n=110), the rates were somewhat different at 31.8%, 11.8%, and 10.0%, respectively, but the difference was not statistically significant (P=.395).

For the subgroups based on the main clinical symptoms, the percentage of lesions having at least 1 positive KOH test from the 3 samples was 35.7% for the keratotic lesions (n=28). This rate was lower than macerated lesions (n=38) and desquamating or scaling lesions (n=132), which were 52.6% and 59.1%, respectively (Table 2). On the other hand, the percentage of lesions that produced only 1 or 2 positive KOH tests from the 3 samples was 25.0% for the keratotic lesions, which was higher than the rates for the macerated lesions and the desquamating or scaling lesions (13.1% and 18.9%, respectively). In particular, the difference between the keratotic lesions and the desquamating or scaling lesions in the distribution of the rates of 0, 1, 2, and 3 positive KOH tests was statistically significant (P=.019). The macerated, desquamating or scaling, keratotic, and blistering lesions are presented in the Figure.

Comment

In the current study, we aimed to investigate if successive KOH tests provide an incremental diagnostic yield in the management of patients with clinically suspected tinea pedis and if these results differ among the subgroups of patients. Both in the evaluation taking into account the order of sampling and in the evaluation disregarding this order, we found that the second sample was necessary for all subgroups, and even the third sample was necessary for patients with keratotic lesions. The main limitation of the study was that we lacked a gold-standard technique (eg, a molecular-based technique); therefore, we are unable to comment on the false-negative and false-positive results of the successive KOH testing.

Summerbell et al¹¹ found in their study that in initial specimens of toenails with apparent lesions taken from 473 patients, the KOH test was 73.8% sensitive for dermatophytes, and this rate was only somewhat higher for cultures (74.6%). Arabatzis et al² investigated 92 skin, nail, and hair specimens from 67 patients with suspected dermatophytosis and found that the KOH test was superior to culture for the detection of dermatophytes (43% vs 33%). Moreover and more importantly, they noted that a real-time polymerase chain reaction (PCR) assay yielded a higher detection rate (51%).² In another study, Wisselink et al³ examined 1437 clinical samples and demonstrated a great increase in the detection of dermatophytes using a real-time PCR assay (48.5%) compared to culture (26.9%). However, PCR may not reflect active disease and could lead to false-positive results.^2,3 Therefore, the aforementioned weakness of our study will be overcome in further studies investigating the benefit of successive KOH testing compared to a molecular-based assay, such as the real-time PCR assay.

In this study, repeating the KOH test provided better results for achieving the diagnosis of tinea pedis in a large number of samples from clinically suspected lesions. Additionally, the distribution of 3, 2, or 1 positive results on the 3 KOH tests was different among the subgroups of lesions. Overall, positivity was less frequent in the keratotic lesions compared to the macerated or desquamating or scaling lesions. Moreover, positivity on all 3 tests also was less frequent in the keratotic lesions. Inversely, the frequency of samples with only 1 or 2 positive results was higher in this subgroup. The necessity for the second, even the third, tests was greater in this subgroup.

Our findings were consistent with the results of the studies performed with successive mycological tests on the nail specimens. Meireles et al¹ repeated 156 mycological nail tests 3 times and found the rate of positivity in the first test to be 19.9%. When the results of the first and second tests were combined, this rate increased to 28.2%, and when the results of all 3 tests were combined, it increased to 37.8%.¹ Gupta¹⁰ demonstrated that even a fourth culture provided an incremental diagnostic yield in the diagnosis of onychomycosis, yet 4 cultures may not be clinically practical. Furthermore, periodic acid–Schiff staining is a more effective measure of positivity in onychomycosis.¹⁵

Although the overall rate of positivity on the 3 tests in our study was unsurprisingly higher in lesions rated highly suspicious for a fungal infection, the rate of only 1 or 2 positive tests was surprisingly somewhat higher in low-suspicion lesions, which suggested that repeating the KOH test would be beneficial, even if the clinical suspicion for tinea pedis was low. The novel contribution of this study includes the finding that mycological information was markedly improved in highly suspicious tinea pedis lesions regardless of the infection site (Table 1) by using 3 successive KOH tests; the percentage of lesions with 1, 2, or 3 positive KOH tests was 5.3%, 12.1%, and 47.0%, respectively (Table 2). A single physician from a single geographical location introduces a limitation to the study for a variety of reasons, including bias in the cases chosen and possible overrepresentation of the causative organism due to region-specific incidence. It is unknown how different causative organisms affect KOH results. The lack of fungal culture results limits the value of this information.

Conclusion

In this study, we investigated the benefit of successive KOH testing in the laboratory diagnosis of tinea pedis and found that the use of second samples in particular provided a substantial increase in diagnostic yield. In other words, the utilization of successive KOH testing remarkably improved the diagnosis of tinea pedis. Therefore, we suggest that at least 2 samples of skin scrapings should be taken for the diagnosis of tinea pedis and that the number of samples should be at least 3 for keratotic lesions. However, further study by using a gold-standard method such as a molecular-based assay as well as taking the samples in daily or weekly intervals is recommended to achieve a more reliable result.

Acknowledgment

The authors would like to thank Gökçen Şahin (Adana, Turkey) for providing technical support in direct microscopic examination.

We applaud Kimball et al¹ on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.²

The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.³ The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.³ These findings reveal many potential therapeutic targets for the treatment of HS.

PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.¹ By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.¹

Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,⁴ ustekinumab,⁵ anakinra,⁶ secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.

We applaud Kimball et al¹ on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.²

The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.³ The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.³ These findings reveal many potential therapeutic targets for the treatment of HS.

PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.¹ By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.¹

Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,⁴ ustekinumab,⁵ anakinra,⁶ secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.

We applaud Kimball et al¹ on their report that adalimumab demonstrated clinical improvement in patients with hidradenitis suppurativa (HS) versus placebo in 2 phase 3 trials. Hidradenitis suppurativa is a chronic relapsing condition with painful subcutaneous abscesses, malodorous drainage, sinus tract formation, and scarring that typically occurs in the axillae and anogenital region. It impairs the quality of life for these patients, as evidenced by higher Dermatology Life Quality Index scores compared to psoriasis, pimples, hand rash, atopic eczema, or control.²

The exact pathogenesis of HS is unknown but likely involves a complex interaction of genetic, hormonal, immunologic, and environmental factors.³ The levels of inflammatory cytokines are elevated in HS lesions, specifically IL-1β, tumor necrosis factor α, IL-10, and CXCL9, as well as monokines from IFN-γ, IL-11, and IL-17A. Additionally, the dermis of affected regions contains IL-12– and IL-23–containing macrophages along with IL-17–producing T cells.³ These findings reveal many potential therapeutic targets for the treatment of HS.

PIONEER I and PIONEER II are similarly designed 36-week phase 3 trials of 633 patients with HS who were unresponsive to oral antibiotic treatment.¹ By week 12, a significantly greater proportion of patients receiving adalimumab demonstrated clinical improvement (≥50% reduction in total abscess and nodule count) compared to placebo in both trials (PIONEER I: 41.8% vs 26.0%, P=.003; PIONEER II: 58.9% vs 27.6%, P<.001). Secondary end points (inflammatory-nodule count, pain score, and disease severity) were only achieved in PIONEER II. The difference in clinical improvement between the trials is likely due to higher baseline disease severity in the HS patients in PIONEER I versus PIONEER II. No new safety risks were reported and were in accordance with prior adalimumab trials for other diseases. Notably, 10 paradoxical psoriasislike eruptions were reported.¹

Adalimumab is the first and only US Food and Drug Administration–approved therapy for HS. Further understanding of the pathogenesis of HS may result in additional biologic treatments for HS. We encourage the manufacturers of other biologic therapies, such as infliximab,⁴ ustekinumab,⁵ anakinra,⁶ secukinumab, ixekizumab, and brodalumab, to consider conducting further clinical trials in HS to enhance the therapeutic options available for this debilitating disease.

Avène A-OXitive

Pierre Fabre Dermo-Cosmetique introduces Avène A-OXitive Antioxidant Defense Serum and Avène A-OXitive Antioxidant Water-Cream to fight against oxidative stress. Stable forms of time-released vitamin E and vitamin C work synergistically to defend against environmental aggressors without irritation. Both products contain hyaluronic acid to visibly plump and firm the skin and soothing Avène thermal spring water to soften and restore the skin’s balance. To preserve stability, each formula comes in an airless pump bottle. For more information, visit www.aveneusa.com.

Orencia

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Orencia (abatacept) for the treatment of adults with active psoriatic arthritis. Orencia is available in both intravenous and subcutaneous injection formulations. It should not be administered concomitantly with tumor necrosis factor antagonists and is not recommended for use with other biologic rheumatoid arthritis therapy. Orencia also is indicated for the treatment of adult rheumatoid arthritis and juvenile idiopathic arthritis. For more information, visit www.orenciahcp.com.

Tremfya

Janssen Biotech, Inc, announces US Food and Drug Administration approval of Tremfya (guselkumab) for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Tremfya is a biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis. Tremfya is administered as a 100-mg subcutaneous injection every 8 weeks, following 2 starter doses at weeks 0 and 4. Clinical studies documented skin clearance at week 16 and up to week 48. For more information, visit www.tremfyahcp.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Avène A-OXitive

Pierre Fabre Dermo-Cosmetique introduces Avène A-OXitive Antioxidant Defense Serum and Avène A-OXitive Antioxidant Water-Cream to fight against oxidative stress. Stable forms of time-released vitamin E and vitamin C work synergistically to defend against environmental aggressors without irritation. Both products contain hyaluronic acid to visibly plump and firm the skin and soothing Avène thermal spring water to soften and restore the skin’s balance. To preserve stability, each formula comes in an airless pump bottle. For more information, visit www.aveneusa.com.

Orencia

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Orencia (abatacept) for the treatment of adults with active psoriatic arthritis. Orencia is available in both intravenous and subcutaneous injection formulations. It should not be administered concomitantly with tumor necrosis factor antagonists and is not recommended for use with other biologic rheumatoid arthritis therapy. Orencia also is indicated for the treatment of adult rheumatoid arthritis and juvenile idiopathic arthritis. For more information, visit www.orenciahcp.com.

Tremfya

Janssen Biotech, Inc, announces US Food and Drug Administration approval of Tremfya (guselkumab) for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Tremfya is a biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis. Tremfya is administered as a 100-mg subcutaneous injection every 8 weeks, following 2 starter doses at weeks 0 and 4. Clinical studies documented skin clearance at week 16 and up to week 48. For more information, visit www.tremfyahcp.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Avène A-OXitive

Pierre Fabre Dermo-Cosmetique introduces Avène A-OXitive Antioxidant Defense Serum and Avène A-OXitive Antioxidant Water-Cream to fight against oxidative stress. Stable forms of time-released vitamin E and vitamin C work synergistically to defend against environmental aggressors without irritation. Both products contain hyaluronic acid to visibly plump and firm the skin and soothing Avène thermal spring water to soften and restore the skin’s balance. To preserve stability, each formula comes in an airless pump bottle. For more information, visit www.aveneusa.com.

Orencia

Bristol-Myers Squibb Company announces US Food and Drug Administration approval of Orencia (abatacept) for the treatment of adults with active psoriatic arthritis. Orencia is available in both intravenous and subcutaneous injection formulations. It should not be administered concomitantly with tumor necrosis factor antagonists and is not recommended for use with other biologic rheumatoid arthritis therapy. Orencia also is indicated for the treatment of adult rheumatoid arthritis and juvenile idiopathic arthritis. For more information, visit www.orenciahcp.com.

Tremfya

Janssen Biotech, Inc, announces US Food and Drug Administration approval of Tremfya (guselkumab) for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Tremfya is a biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis. Tremfya is administered as a 100-mg subcutaneous injection every 8 weeks, following 2 starter doses at weeks 0 and 4. Clinical studies documented skin clearance at week 16 and up to week 48. For more information, visit www.tremfyahcp.com.

If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].

Clinicians who have attempted to perform an in-office procedure on infants or young children will recognize the difficulties that arise from the developmental inability to cooperate with procedures.¹ Potential problems mentioned in the literature include but are not limited to anxiety, which is identified in all age groups of patients undergoing dermatologic procedures²; limitation of pain control³; and poor outcomes due to movement by the patient.¹ In one author’s experience (N.B.S.), anxious and scared children can potentially cause injury to themselves, parents/guardians, and health care professionals by flailing and kicking; children are flexible and can wriggle out of even fine grips, and some children, especially toddlers, can be strong.

The usage of topical anesthetics can only give superficial anesthesia. They can ostensibly reduce pain and are useful for anesthesia of curettage, but their use is limited in infants and young children by the minimal amount of drug that is safe for application, as risks of absorption include methemoglobinemia and seizure activity, and especially by lack of cooperation by the child.⁴ Infiltrative anesthesia is needed for adequate pain control in addition to a topical anesthetic for many procedures.³

General anesthesia seems to be the best alternative due to associated amnesia of the events occurring including pain; immobilization and ability to produce more accurate biopsy sampling; better immobilization leading to superior cosmetic results; and reduced risk to patients, parents/guardians, and health care professionals from a flailing child. In the field of pediatric dermatology, general anesthesia often is used for excision of larger lesions and cosmetic repairs. Operating room privileges are not always easy to obtain, but many pediatric dermatologists take advantage of outpatient surgical centers associated with their medical center. A retrospective review of 226 children receiving 681 procedures at a single institution documented low rates of complications.¹

If it was that easy, most children would be anesthetized with general anesthesia. However, there are risks associated with general anesthesia. Parents/guardians often will do what they can to avoid risk and may therefore refuse general anesthesia, but it is not completely avoidable in complicated skin disease. Despite the risks, the benefit is present in a major anomaly correction such as a cleft palate in a 6-month-old but may not be there for the treatment of a wart. When procedures are nonessential or may be conducted without anesthesia, avoidance of general anesthesia is reasonable and a combination of topical and local infiltrative anesthesia can help. In the American Academy of Dermatology guidelines on in-office anesthesia, Kouba et al⁵ states: “Topical agents are recommended as a first-line method of anesthesia for the repair of dermal lacerations in children and for other minor dermatologic procedures, including curettage. For skin biopsy, excision, or other cases where topical agents alone are insufficient, adjunctive use of topical anesthesia to lessen the discomfort of infiltrative anesthetic should be considered.”

A new controversy recently has emerged concerning the potential risks of anesthesia on neurocognitive development in infants and young children. These concerns regardingthe labeling changes of anesthetic and sedation drugs by the US Food and Drug Administration (FDA) in December 2016 specifically focused on these risks in children younger than 3 years with prolonged (>3 hours) and repeated exposures; however, this kind of exposure is unlikely with standard pediatric dermatologic procedures.^6-9

There is compelling evidence from animal studies that exposure to all anesthetic agents in clinical use induces neurotoxicity and long-term adverse neurobehavioral deficits; however, whether these findings are applicable in human infants is unknown.^6-9 Most of the studies in humans showing adverse outcomes have been retrospective observational studies subject to multiple sources of bias. Two recent large clinical studies—the GAS (General Anaesthesia compared to Spinal anaesthesia) trial¹⁰ and the PANDA (Pediatric Anesthesia and Neurodevelopment Assessment) study¹¹—have shown no evidence of abnormal neurocognitive effects with a single brief exposure before 3 years of age (PANDA) or during infancy (GAS) in otherwise-healthy children.^10,11

It is important to note that the FDA labeling change warning specifically stated that “[c]onsistent with animal studies, recent human data suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” Moreover, the FDA emphasized that “Surgeries or procedures in children younger than 3 years should not be delayed or avoided when medically necessary.”¹² Taking these points into consideration, we should offer our patients in-office care when possible and postpone elective procedures when advisable but proceed when necessary for our patients’ physical and emotional health.

Clinicians who have attempted to perform an in-office procedure on infants or young children will recognize the difficulties that arise from the developmental inability to cooperate with procedures.¹ Potential problems mentioned in the literature include but are not limited to anxiety, which is identified in all age groups of patients undergoing dermatologic procedures²; limitation of pain control³; and poor outcomes due to movement by the patient.¹ In one author’s experience (N.B.S.), anxious and scared children can potentially cause injury to themselves, parents/guardians, and health care professionals by flailing and kicking; children are flexible and can wriggle out of even fine grips, and some children, especially toddlers, can be strong.

The usage of topical anesthetics can only give superficial anesthesia. They can ostensibly reduce pain and are useful for anesthesia of curettage, but their use is limited in infants and young children by the minimal amount of drug that is safe for application, as risks of absorption include methemoglobinemia and seizure activity, and especially by lack of cooperation by the child.⁴ Infiltrative anesthesia is needed for adequate pain control in addition to a topical anesthetic for many procedures.³

General anesthesia seems to be the best alternative due to associated amnesia of the events occurring including pain; immobilization and ability to produce more accurate biopsy sampling; better immobilization leading to superior cosmetic results; and reduced risk to patients, parents/guardians, and health care professionals from a flailing child. In the field of pediatric dermatology, general anesthesia often is used for excision of larger lesions and cosmetic repairs. Operating room privileges are not always easy to obtain, but many pediatric dermatologists take advantage of outpatient surgical centers associated with their medical center. A retrospective review of 226 children receiving 681 procedures at a single institution documented low rates of complications.¹

If it was that easy, most children would be anesthetized with general anesthesia. However, there are risks associated with general anesthesia. Parents/guardians often will do what they can to avoid risk and may therefore refuse general anesthesia, but it is not completely avoidable in complicated skin disease. Despite the risks, the benefit is present in a major anomaly correction such as a cleft palate in a 6-month-old but may not be there for the treatment of a wart. When procedures are nonessential or may be conducted without anesthesia, avoidance of general anesthesia is reasonable and a combination of topical and local infiltrative anesthesia can help. In the American Academy of Dermatology guidelines on in-office anesthesia, Kouba et al⁵ states: “Topical agents are recommended as a first-line method of anesthesia for the repair of dermal lacerations in children and for other minor dermatologic procedures, including curettage. For skin biopsy, excision, or other cases where topical agents alone are insufficient, adjunctive use of topical anesthesia to lessen the discomfort of infiltrative anesthetic should be considered.”

A new controversy recently has emerged concerning the potential risks of anesthesia on neurocognitive development in infants and young children. These concerns regardingthe labeling changes of anesthetic and sedation drugs by the US Food and Drug Administration (FDA) in December 2016 specifically focused on these risks in children younger than 3 years with prolonged (>3 hours) and repeated exposures; however, this kind of exposure is unlikely with standard pediatric dermatologic procedures.^6-9

There is compelling evidence from animal studies that exposure to all anesthetic agents in clinical use induces neurotoxicity and long-term adverse neurobehavioral deficits; however, whether these findings are applicable in human infants is unknown.^6-9 Most of the studies in humans showing adverse outcomes have been retrospective observational studies subject to multiple sources of bias. Two recent large clinical studies—the GAS (General Anaesthesia compared to Spinal anaesthesia) trial¹⁰ and the PANDA (Pediatric Anesthesia and Neurodevelopment Assessment) study¹¹—have shown no evidence of abnormal neurocognitive effects with a single brief exposure before 3 years of age (PANDA) or during infancy (GAS) in otherwise-healthy children.^10,11

It is important to note that the FDA labeling change warning specifically stated that “[c]onsistent with animal studies, recent human data suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” Moreover, the FDA emphasized that “Surgeries or procedures in children younger than 3 years should not be delayed or avoided when medically necessary.”¹² Taking these points into consideration, we should offer our patients in-office care when possible and postpone elective procedures when advisable but proceed when necessary for our patients’ physical and emotional health.

Clinicians who have attempted to perform an in-office procedure on infants or young children will recognize the difficulties that arise from the developmental inability to cooperate with procedures.¹ Potential problems mentioned in the literature include but are not limited to anxiety, which is identified in all age groups of patients undergoing dermatologic procedures²; limitation of pain control³; and poor outcomes due to movement by the patient.¹ In one author’s experience (N.B.S.), anxious and scared children can potentially cause injury to themselves, parents/guardians, and health care professionals by flailing and kicking; children are flexible and can wriggle out of even fine grips, and some children, especially toddlers, can be strong.

The usage of topical anesthetics can only give superficial anesthesia. They can ostensibly reduce pain and are useful for anesthesia of curettage, but their use is limited in infants and young children by the minimal amount of drug that is safe for application, as risks of absorption include methemoglobinemia and seizure activity, and especially by lack of cooperation by the child.⁴ Infiltrative anesthesia is needed for adequate pain control in addition to a topical anesthetic for many procedures.³

General anesthesia seems to be the best alternative due to associated amnesia of the events occurring including pain; immobilization and ability to produce more accurate biopsy sampling; better immobilization leading to superior cosmetic results; and reduced risk to patients, parents/guardians, and health care professionals from a flailing child. In the field of pediatric dermatology, general anesthesia often is used for excision of larger lesions and cosmetic repairs. Operating room privileges are not always easy to obtain, but many pediatric dermatologists take advantage of outpatient surgical centers associated with their medical center. A retrospective review of 226 children receiving 681 procedures at a single institution documented low rates of complications.¹

If it was that easy, most children would be anesthetized with general anesthesia. However, there are risks associated with general anesthesia. Parents/guardians often will do what they can to avoid risk and may therefore refuse general anesthesia, but it is not completely avoidable in complicated skin disease. Despite the risks, the benefit is present in a major anomaly correction such as a cleft palate in a 6-month-old but may not be there for the treatment of a wart. When procedures are nonessential or may be conducted without anesthesia, avoidance of general anesthesia is reasonable and a combination of topical and local infiltrative anesthesia can help. In the American Academy of Dermatology guidelines on in-office anesthesia, Kouba et al⁵ states: “Topical agents are recommended as a first-line method of anesthesia for the repair of dermal lacerations in children and for other minor dermatologic procedures, including curettage. For skin biopsy, excision, or other cases where topical agents alone are insufficient, adjunctive use of topical anesthesia to lessen the discomfort of infiltrative anesthetic should be considered.”

A new controversy recently has emerged concerning the potential risks of anesthesia on neurocognitive development in infants and young children. These concerns regardingthe labeling changes of anesthetic and sedation drugs by the US Food and Drug Administration (FDA) in December 2016 specifically focused on these risks in children younger than 3 years with prolonged (>3 hours) and repeated exposures; however, this kind of exposure is unlikely with standard pediatric dermatologic procedures.^6-9

There is compelling evidence from animal studies that exposure to all anesthetic agents in clinical use induces neurotoxicity and long-term adverse neurobehavioral deficits; however, whether these findings are applicable in human infants is unknown.^6-9 Most of the studies in humans showing adverse outcomes have been retrospective observational studies subject to multiple sources of bias. Two recent large clinical studies—the GAS (General Anaesthesia compared to Spinal anaesthesia) trial¹⁰ and the PANDA (Pediatric Anesthesia and Neurodevelopment Assessment) study¹¹—have shown no evidence of abnormal neurocognitive effects with a single brief exposure before 3 years of age (PANDA) or during infancy (GAS) in otherwise-healthy children.^10,11

It is important to note that the FDA labeling change warning specifically stated that “[c]onsistent with animal studies, recent human data suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” Moreover, the FDA emphasized that “Surgeries or procedures in children younger than 3 years should not be delayed or avoided when medically necessary.”¹² Taking these points into consideration, we should offer our patients in-office care when possible and postpone elective procedures when advisable but proceed when necessary for our patients’ physical and emotional health.

Adults who were previously employed are twice as likely to report daily or almost-daily pain than are those who are currently employed, according to the Centers for Disease Control and Prevention.

In an ongoing survey, just over 30% of adults aged 18 years and older who were previously employed reported that they experienced pain on “most days or every day” in the past 6 months, compared with 15% of those who were currently employed and 19% of those classified as never employed, investigators from the CDC estimated (MMWR. 2017 Jul 28;66[29]:796).

[email protected]

Adults who were previously employed are twice as likely to report daily or almost-daily pain than are those who are currently employed, according to the Centers for Disease Control and Prevention.

In an ongoing survey, just over 30% of adults aged 18 years and older who were previously employed reported that they experienced pain on “most days or every day” in the past 6 months, compared with 15% of those who were currently employed and 19% of those classified as never employed, investigators from the CDC estimated (MMWR. 2017 Jul 28;66[29]:796).

[email protected]

Adults who were previously employed are twice as likely to report daily or almost-daily pain than are those who are currently employed, according to the Centers for Disease Control and Prevention.

In an ongoing survey, just over 30% of adults aged 18 years and older who were previously employed reported that they experienced pain on “most days or every day” in the past 6 months, compared with 15% of those who were currently employed and 19% of those classified as never employed, investigators from the CDC estimated (MMWR. 2017 Jul 28;66[29]:796).

[email protected]

Table of Contents

• The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA
• Systems Automation for Cancer Surveillance: A Lean Six Sigma Project for Tracking Care of Patients With Head and Neck Cancer
• Open Clinical Trials for Patients With Renal Cell Carcinoma
• Innovations Lead to More Targeted Prostate Cancer Treatments
• Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care
• Acute Leukemia of Ambiguous Lineage in Elderly Patients: A SEER Medicare Database Analysis
• Treatment and Management of Patients With Non-Small Cell Lung Cancer
• Do Erythropoiesis-Stimulating Agents Have a Risk Evaluation and Mitigation Strategy?

Table of Contents

• The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA
• Systems Automation for Cancer Surveillance: A Lean Six Sigma Project for Tracking Care of Patients With Head and Neck Cancer
• Open Clinical Trials for Patients With Renal Cell Carcinoma
• Innovations Lead to More Targeted Prostate Cancer Treatments
• Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care
• Acute Leukemia of Ambiguous Lineage in Elderly Patients: A SEER Medicare Database Analysis
• Treatment and Management of Patients With Non-Small Cell Lung Cancer
• Do Erythropoiesis-Stimulating Agents Have a Risk Evaluation and Mitigation Strategy?

Table of Contents

• The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA
• Systems Automation for Cancer Surveillance: A Lean Six Sigma Project for Tracking Care of Patients With Head and Neck Cancer
• Open Clinical Trials for Patients With Renal Cell Carcinoma
• Innovations Lead to More Targeted Prostate Cancer Treatments
• Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care
• Acute Leukemia of Ambiguous Lineage in Elderly Patients: A SEER Medicare Database Analysis
• Treatment and Management of Patients With Non-Small Cell Lung Cancer
• Do Erythropoiesis-Stimulating Agents Have a Risk Evaluation and Mitigation Strategy?

“Chronic Lyme disease” is sometimes a catchall diagnosis for patients with a wide spectrum of musculoskeletal and neuropsychiatric symptoms, fatigue, and generalized pain. That, in turn, has led to a variety of treatments: courses of antibiotics lasting for months to years, IV infusions of hydrogen peroxide, immunoglobulin therapy, even stem cell transplants. Those treatments, though, may not lead to substantial long-term improvement—in fact, they can be harmful.

Clinicians, health departments, and patients have contacted the CDC reporting life-threatening complications resulting from treatment for chronic Lyme disease, including metastatic bacterial infections, septic shock, Clostridium difficile (C diff) colitis, and abscess. An article in Morbidity and Mortality Weekly Report (MMWR) described 5 cases that “highlight the severity and scope” of adverse effects caused by the use of unproven treatments for chronic Lyme disease.

 One patient with fatigue and joint pain, was diagnosed with chronic Lyme disease, babesiosis, and Bartonella infection. When the symptoms worsened despite multiple courses of oral antibiotics, the patient was switched to IV ceftriaxone and cefotaxime. However, the pain did not lessen; the patient became hypotensive and tachycardic and was placed in intensive care. Her condition continued to worsen, and she died. The patient’s death was attributed to septic shock related to central venous catheter–associated bacteremia.

In another case, a woman was first diagnosed with amyotrophic lateral sclerosis, then as a second opinion, with chronic Lyme disease. After 7 months of intensive antimicrobial treatment, the pain improved but she got weaker. She also developed intractable C diff infection that required prolonged treatment. However, the patient died of complications of amyotrophic lateral sclerosis—an example, the researchers say, of a missed opportunity for appropriate treatment due to misdiagnosis.

Antibiotics and immunoglobulin therapies are effective and necessary treatments for many conditions, MMWR emphasized—“however, unnecessary antibiotic and immunoglobulin use provides no benefit to patients while putting them at risk for adverse events.”

“Chronic Lyme disease” is sometimes a catchall diagnosis for patients with a wide spectrum of musculoskeletal and neuropsychiatric symptoms, fatigue, and generalized pain. That, in turn, has led to a variety of treatments: courses of antibiotics lasting for months to years, IV infusions of hydrogen peroxide, immunoglobulin therapy, even stem cell transplants. Those treatments, though, may not lead to substantial long-term improvement—in fact, they can be harmful.

Clinicians, health departments, and patients have contacted the CDC reporting life-threatening complications resulting from treatment for chronic Lyme disease, including metastatic bacterial infections, septic shock, Clostridium difficile (C diff) colitis, and abscess. An article in Morbidity and Mortality Weekly Report (MMWR) described 5 cases that “highlight the severity and scope” of adverse effects caused by the use of unproven treatments for chronic Lyme disease.

 One patient with fatigue and joint pain, was diagnosed with chronic Lyme disease, babesiosis, and Bartonella infection. When the symptoms worsened despite multiple courses of oral antibiotics, the patient was switched to IV ceftriaxone and cefotaxime. However, the pain did not lessen; the patient became hypotensive and tachycardic and was placed in intensive care. Her condition continued to worsen, and she died. The patient’s death was attributed to septic shock related to central venous catheter–associated bacteremia.

In another case, a woman was first diagnosed with amyotrophic lateral sclerosis, then as a second opinion, with chronic Lyme disease. After 7 months of intensive antimicrobial treatment, the pain improved but she got weaker. She also developed intractable C diff infection that required prolonged treatment. However, the patient died of complications of amyotrophic lateral sclerosis—an example, the researchers say, of a missed opportunity for appropriate treatment due to misdiagnosis.

Antibiotics and immunoglobulin therapies are effective and necessary treatments for many conditions, MMWR emphasized—“however, unnecessary antibiotic and immunoglobulin use provides no benefit to patients while putting them at risk for adverse events.”

“Chronic Lyme disease” is sometimes a catchall diagnosis for patients with a wide spectrum of musculoskeletal and neuropsychiatric symptoms, fatigue, and generalized pain. That, in turn, has led to a variety of treatments: courses of antibiotics lasting for months to years, IV infusions of hydrogen peroxide, immunoglobulin therapy, even stem cell transplants. Those treatments, though, may not lead to substantial long-term improvement—in fact, they can be harmful.

Clinicians, health departments, and patients have contacted the CDC reporting life-threatening complications resulting from treatment for chronic Lyme disease, including metastatic bacterial infections, septic shock, Clostridium difficile (C diff) colitis, and abscess. An article in Morbidity and Mortality Weekly Report (MMWR) described 5 cases that “highlight the severity and scope” of adverse effects caused by the use of unproven treatments for chronic Lyme disease.

 One patient with fatigue and joint pain, was diagnosed with chronic Lyme disease, babesiosis, and Bartonella infection. When the symptoms worsened despite multiple courses of oral antibiotics, the patient was switched to IV ceftriaxone and cefotaxime. However, the pain did not lessen; the patient became hypotensive and tachycardic and was placed in intensive care. Her condition continued to worsen, and she died. The patient’s death was attributed to septic shock related to central venous catheter–associated bacteremia.

In another case, a woman was first diagnosed with amyotrophic lateral sclerosis, then as a second opinion, with chronic Lyme disease. After 7 months of intensive antimicrobial treatment, the pain improved but she got weaker. She also developed intractable C diff infection that required prolonged treatment. However, the patient died of complications of amyotrophic lateral sclerosis—an example, the researchers say, of a missed opportunity for appropriate treatment due to misdiagnosis.

Antibiotics and immunoglobulin therapies are effective and necessary treatments for many conditions, MMWR emphasized—“however, unnecessary antibiotic and immunoglobulin use provides no benefit to patients while putting them at risk for adverse events.”

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).

The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.

Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.

The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.

Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.

Companion diagnostic

Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.

The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.

Enasidenib is licensed from Agios Pharmaceuticals.

Trial results

The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).

Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.

The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.

The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.

The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.

The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).

For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).

Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.

Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.

Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).

The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.

Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.

The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).

The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.

Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.

The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.

Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.

Companion diagnostic

Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.

The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.

Enasidenib is licensed from Agios Pharmaceuticals.

Trial results

The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).

Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.

The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.

The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.

The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.

The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).

For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).

Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.

Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.

Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).

The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.

Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.

The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved marketing of the oral IDH2 inhibitor enasidenib (IDHIFA®).

The drug is now approved to treat adults with relapsed or refractory acute myeloid leukemia (AML) and an IDH2 mutation, as detected by an FDA-approved test.

Enasidenib is available in 50 mg and 100 mg tablets. The recommended dose is 100 mg once daily until disease progression or unacceptable toxicity.

The prescribing information for enasidenib includes a boxed warning that the drug may cause differentiation syndrome, and this adverse event (AE) can be fatal if not treated.

Signs and symptoms of differentiation syndrome may include fever, dyspnea, acute respiratory distress, radiographic pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, and hepatic, renal, or multi-organ dysfunction. At first suspicion of symptoms, doctors should treat patients with corticosteroids and monitor patients closely until symptoms resolve.

Companion diagnostic

Enasidenib was approved concurrently with the Abbott RealTime™ IDH2 companion diagnostic test, which was approved as an aid in identifying AML patients for treatment with enasidenib.

The FDA granted approval of enasidenib to Celgene Corporation and approval of the RealTime IDH2 Assay to Abbott Laboratories.

Enasidenib is licensed from Agios Pharmaceuticals.

Trial results

The FDA’s approval of enasidenib and the companion diagnostic test was based on data from a phase 1/2 trial (Study AG221-C-001, NCT01915498).

Data from this trial were recently presented at the ASCO 2017 Annual Meeting. However, the definitive data are included in the prescribing information for enasidenib.

The prescribing information includes efficacy data for 199 adults with relapsed/refractory AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime™ IDH2 test.

The 199 patients received enasidenib at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects.

The patients’ median age was 68 (range, 19 to 100). They received a median of 2 prior anticancer regimens (range, 1 to 6). More than half (52%) were refractory to previous therapy.

The rate of complete response (CR) or CR with partial hematologic improvement (CRh) was 23% (n=46). The median duration of CR/CRh was 8.2 months (range, 4.3 to 19.4).

For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5), and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2).

Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day period post-baseline.

Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.

Researchers evaluated the safety of enasidenib in 214 patients. The median duration of exposure to enasidenib was 4.3 months (range, 0.3 to 23.6).

The most common AEs of any grade (≥20%) were nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.

Serious AEs were reported in 77.1% of patients. The most frequent serious AEs (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.

The 30-day and 60-day mortality rates were 4.2% (9/214) and 11.7% (25/214), respectively.

Photo courtesy of the CDC

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

Photo courtesy of the CDC

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

Photo courtesy of the CDC

A diagnosis of delirium during a visit to the emergency department (ED) is a poor prognostic factor for patients with advanced cancer, according to research published in The Oncologist.

The study showed that patients with advanced cancer who were diagnosed with delirium during an ED visit were more likely to be admitted to the hospital or intensive care unit (ICU) and more likely to die earlier than patients without delirium.

This shows the importance of accurately diagnosing delirium in advanced cancer patients, said Ahmed Elsayem, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Previous studies have shown that delirium is associated with poor survival in advanced cancer patients being treated in ICUs or receiving palliative care in hospices, but no one had investigated whether the same was true for patients visiting EDs.

“To the best our knowledge, this is the first study to show the poor survival of advanced cancer patients in the emergency department setting,” Dr Elsayem said.

He and his colleagues previously conducted a study in which they assessed the frequency of delirium in advanced cancer patients visiting the ED at MD Anderson. The researchers tested for delirium using 2 questionnaires—the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS).

Questioning 243 patients in total, the team found that 44 patients, or 18%, were suffering with delirium according to at least 1 of the questionnaires.

In the current study, Dr Elsayem and his colleagues determined how many of these cancer patients, with and without delirium, were subsequently admitted to hospital and ICUs, as well as how long the patients lived after their visit to the ED.

Results

The rate of hospitalization was 82% among patients with delirium according to CAM and/or MDAS, 77% among patients with delirium according to MDAS only, and 49% among patients without delirium (P=0.0013). Rates of ICU admission were 18%, 14%, and 2%, respectively (P=0.0004).

The median overall survival was 1.23 months for patients with delirium according to CAM and/or MDAS, 4.70 months for patients with delirium according to MDAS only, and 10.45 months for patients without delirium. The difference between the patients with and without delirium was significant (P<0.0001).

Given the influence delirium appears to have on survival, Dr Elsayem said prompt diagnosis and management in hospital EDs is essential.

He noted that, in many cases, delirium in advanced cancer patients can be resolved by simply stopping or modifying their medication and treating any associated infections.

“Treating the triggers if known—such as stopping medications—is the main treatment for an episode of delirium,” Dr Elsayem said.

He also suggested that further research needs to be done on this topic, including conducting similar studies on delirium in advanced cancer patients in other EDs and with larger groups of patients.

Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.

Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.

Mantle cell lymphoma

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to acalabrutinib, a BTK inhibitor being developed to treat multiple B-cell malignancies.

The breakthrough designation applies to acalabrutinib as a treatment for patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as a rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

The FDA granted acalabrutinib breakthrough designation based on data from the drug’s development program, which includes data from the phase 2 ACE-LY-004 trial in patients with relapsed or refractory MCL.

Data from this trial have not yet been released to the public but are expected to be presented at an upcoming medical meeting.