Senna Alata Leaf Decoction as a Treatment for Tinea Imbricata
Senna Alata Leaf Decoction as a Treatment for Tinea Imbricata
Background: Tinea imbricata ("tokelau") is a rare form of tinea corporis which is caused by
 Trichophyton concentricum. It is endemic among the T'boli tribe in Sarangani, Philippines .
 Temporary remissions, despite antifungal treatment, can be attributed to factors such as
 genetic susceptibility, widespread poverty, poor hygienic conditions and overcrowding.
 Limited access to commercial antifungal medications makes the treatment of tinea imbricata a
 pressing public health concern.

 Senna alata grows abundantly in the areas where the T'boli tribe resides. Anecdotal reports
 about its efficacy as a treatment for tinea imbricata exist and need to be further validated.

 Objective: This study aims to assess the efficacy and safety of a community-prepared Senna
 alata leaf decoction in the treatment of tinea imbricata.

 Methods: This study is a preliminary open label, before and after clinical trial. Enrolled
 patients were taught how to make Senna alata leaf decoction and were asked to apply it as a
 leave-on body wash once a day for 28+/-3 days. Disease severity, pruritus visual analogue
 scale scores (VAS) and potassium hydroxide smear (KOH) of the skin scrapings were evaluated
 before and after treatment. Two separate assessors evaluated post treatment severity based on
 standard photographs. Diagnostic concordance was determined using Cohen's kappa statistics.
 Wilcoxon paired signed-rank test was used to analyzed before and after clinical parameter
 scores. Adverse drug events were recorded.
Introduction:

 Tinea imbricata is a rare form of tinea corporis caused by Trichophyton concentricum, an
 anthropophilic dermatophyte. Its lesions would present embossed "maze-like" or lace-like
 pattern of embosed concentric rings mainly on the trunk and extensor surfaces of both
 extremities, sparing the palms, soles, hair and nails. Due to the rarity of the disease,
 limited epidemiologic and prevalence studies exist. (Halickova, 2008) Tine imbricata is known
 to be endemic in places such as the Paciﬁc Islands of Oceana, South East Asia, India,
 Sri-Lanka, North, Central and South America. (Halickova, 2008 and Pihet, 2008) The first case
 was discovered in the southern Philippines by William Dampier in 1789. (Fernandez, 1962) In
 2010, cases of tinea imbricata were found to still exist among T'boli tribe who live in the
 mountainous areas of Kiamba in Sarangani through the University of the Philippines-
 Department of Science and Technology (UP-DOST) telemedicine project. (Carpio, 2010) The
 inherited susceptibility of T.concentricum infection may explain why the disease affects only
 specific group of people. The most accepted inheritance pattern is autosomal recessive
 attributing to the inherited defect in cell-mediated immunity, which results to failure of
 the T-lymphocytes to become sensitized to the fungi and mount an immune response. Majority of
 the patients are blood-related individuals and rarely infect unrelated individuals even after
 close contact or cohabitation., Other risk factors are isolated and primitive living
 conditions especially in humid areas, widespread poverty, poor hygienic conditions and
 overcrowding. (Bonifaz, 2003 and Bonifaz, 2004) Antifungals are the mainstay treatment
 against Trichophyton concentricum. Griseofulvin, 500 mg/tab twice daily, and terbinafine, 250
 mg once daily, for at least 4 weeks result to complete resolution. (Wingfield, 2004) However,
 these commercial antifungal preparations are costly and not readily available in the health
 centers of Sarangani. Furthermore, even with systemic antifungal intake, disease remission
 would only last for at least 8 weeks post-treatment. Alternative treatment options that will
 promote clearance of the infection that are accessible, inexpensive and practical to use
 should be explored.

 Antifungals from local plant sources are one of the potential alternatives. Among these,
 Senna alata has validated efficacy on superficial dermatophytic infections and is included in
 the Philippine National Drug Formulary. It is a tropical ornamental shrub, also known as
 candle bush and locally as "Akapulko, which grows throughout the low and medium altitude
 areas of the country including Sarangani.

 Chemical screening of the leaves and roots of S. alata revealed the anthraquinones and its
 derivatives such as aloe, emodin, chrysophanol, and rhein, are the major components
 responsible for its antifungal activity. These are naturally occurring phenolic compounds are
 readily oxidized to form a phenolate ion or quinone, which aids in the scavenging and
 entrapment of microorganisms. Furthermore, phenols impair a variety of enzyme systems that
 are involved in the microorganism's energy production. They also disrupt the integrity of the
 cell membrane and interfere with the synthesis of its structural components. (Hemen and
 Ledwani,2012) There were anecdotal reports on the efficacy of akapulko decoction against
 tinea imbricata. A decoction is the liquid resulting from concentrating the essence of the
 substance by heating or boiling, especially a medicinal preparation made from a plant. Plant
 parts such as leaves can be used in decoctions. The first anecdotal report was published by
 Dofitas and Non last 2010. Senna alata leaf decoction was used as leave-on body wash in a
 T'boli woman resulting in complete clearance of the lesions. In the case series by Carpio et.
 al., S. alata leaf decoction resulted to partial improvement of the skin lesions. (Dofitas
 and Non, 2010 and Caprio, 2010) At present there are no existing clinical trials about the
 use of akapulko as an alternative or complementary treatment to tinea imbricata. The
 favorable results from the anecdotal and case series studies pave the way for the
 consideration of akapulko decoction as a part of an accessible and affordable treatment
 regimen for tinea imbricata.

 II Objectives:

 General objectives: This study aims to assess the efficacy and safety of Senna alata leaf
 decoction applied once daily in the treatment of tinea imbricata.

 Specific objectives:

 1. To determine the treatment response at the end of four weeks (28 days +/-3) as measured
 by disease severity, pruritus visual analogue scale score and potassium hydroxide smear
 conversion of the patients with tinea imbricata treated once daily with Senna alata leaf
 decoction

 2. To document the adverse reactions associated with Senna alata leaf decoction
 application.

 III Methods:

 This study was a preliminary open label, before-and after clinical trial. This study took
 place at Kiamba Municipality, Sarangani Province, Mindanao from November 2014 to January
 2015. The duration of patient involvement was 4 weeks (28+3 days). Figure 1 shows the flow
 chart of the study procedure.

 Recruitment of participants: An outreach skin clinic, manned by dermatology residents and
 consultants of the University of the Philippines- Philippine General Hospital, was conducted
 in the local health center. Patients with any skin disease and suspected tinea imbricata
 cases were invited to consult. Patient recruitment began during the outreach mission and was
 continued even thereafter. A consultant investigator assessed eligibility and disease
 severity of the participants, during and even after the outreach mission. Trained research
 assistants collected skin scrapings from active skin lesions of patients.

 Each participant was assigned code numbers written on the case record forms. The
 participants' names with the corresponding numbers were recorded in a separate registry.

 Securing consent and enrolment of participants: All patients with clinically diagnosed tinea
 imbricata and with microscopically positive KOH smear were invited by the investigators to
 join the study. The purpose, duration, benefits and possible adverse effects were explained
 to all participants and signed consent forms were secured by research assistants who could
 speak T'boli dialect. A thumb mark was obtained in place of a signature for illiterate
 participants. (Appendices A, B, and C)

 Enrolled patients were subjected to the following steps before starting therapy:

 1. Detailed history-taking and physical examination

 2. Collection of skin scrapings and microscopic confirmation of fungal elements in skin
 scrapings using potassium hydroxide mount

 3. Accomplishment of the standard case record forms, which details the severity of the
 disease, pruritus VAS score and adverse drug effects. (Appendix D)

 4. Pre-treatment photographic documentation. A written consent was obtained prior to
 photographic documentation of each patient. Photography was done in a private room.

 Application of Akapulko leaf decoction:

 The participants were instructed to take a bath once a day using a syndet bar and to towel
 dry their skin before applying the akapulko decoction. Fresh decoction was prepared by the
 patients every day. After a bath, the patient applied the fresh cooled decoction by hand on
 the whole body especially on the affected areas and left it to dry. Approximately one
 glassful (350ml) of akapulko decoction should be consumed for one whole body application. The
 total duration of daily application should be 4 weeks (28 days +3) until the next outcome
 assessment.

 The patients were given illustrated, laminated instructional materials and a tabulated
 checklist of instructions on how to prepare and apply the akapulko decoction. This served as
 a monitoring sheet of each patient. (Appendix E) The barangay health workers underwent
 hands-on training by the investigators on the preparation of the akapulko leaf decoction.
 Trained research assistants conducted demonstration of the akapulko preparation to the
 enrolled patients. (Appendix F)

 Clinical Parameters: Each patient was assessed based on disease severity based on erythema,
 scaling and area of involvement. (Tables 1-3) Then, composite scores were combined and graded
 no disease, mild, moderate and severe. (Table 4) Pruritus severity was gauge using 10-cm
 pruritus visual analogue scale score. KOH smear of skin scrapings was also done before and
 after treatment.

 Outcome assessment:

 Clinical response to treatment was assessed after 4 weeks. Standard photographs were taken by
 the research assistants for documentation and sent electronically via email to the
 investigators. A panel of two dermatologists who had prior clinical experience with tinea
 imbricata assessed the treatment response based on the digital photographs taken at the end
 of the treatment period. Post-treatment VAS scores were recorded.

 Mycologic cure was assessed as a negative KOH mount after 1 month of treatment in both
 treatment groups. The research aides or the public health nurse collected skin scrapings for
 KOH on the same site as the pre-treatment KOH source. Samples were placed in clean pieces of
 folded bond paper inside a properly sealed envelope and airmailed to the investigators for
 KOH microscopic examination.

 Data management and analysis A standard case record form was used to collect patient data
 (Appendix A). Accomplished records were checked for accuracy and completeness by the
 investigators in the field. Data gathered were encoded in an electronic spreadsheet,
 Microsoft Excel 2011.

 Descriptive analysis was done, which included epidemiologic characteristics, initial disease
 severity, and clinical outcome per patient. Clearance rates were computed after 4 weeks using
 the formulas below.

 Clearance rate = Number of patients who underwent clearance x 100/ Total number of patients
 enrolled

 Partial clearance rate = Number of patients who underwent partial clearance X 100/Total
 number of patients enrolled

 Failure rate = Number of patients who had no improvement + worsening disease severity
 X100/Total number of patients enrolled

 Each patient was classified as with complete clearance, partial clearance or no clearance.
 Subgroup analysis by disease severity was performed. Diagnostic concordance between the two
 consultants who assessed disease severity was determined using Cohen's kappa statistics.
 Wilcoxon paired signed rank test was used to analyzed before and after clinical parameter
 scores. Adverse drug events, reported by the patients, were recorded as a frequency
 distribution.

 Adverse reactions Presence of any adverse reactions was noted. Subjects were instructed to
 report side effects for proper management. (Table 5) Participants with mild to severe adverse
 drug effects were to be withdrawn from the study and provided appropriate management by the
 investigators.

 Ethical considerations:

 This study was conducted in accordance to the guidelines of the Helsinki declaration. The
 study protocol was formulated in accordance to the guidelines imposed by the National Ethical
 Guideline for Health Research published by the Philippine Health Research Ethics Board and
 was conducted upon the approval of the institution's ethics review board. Since indigenous
 people are involved as subjects, this study was approved the National Commission on
 Indigenous People (NCIP). A research grant was received from the Philippine Dermatological
 Society. There were no conflicts of interest in the conduct of this research.
Inclusion Criteria:

 1. Indigenous T'boli patient aged 18 years old and above, male or female

 2. Patients with clinically diagnosed tinea imbricata with microscopically confirmed skin
 scraping positive for potassium hydroxide (KOH)

 Exclusion Criteria:

 1. Patients who were treated or undergoing treatment with topical anti-fungal for 2 weeks
 or oral anti-fungal 1 month before the study

 2. Patients who were taking other systemic medications such as cytotoxic and
 immunosuppressive drugs

 3. Patients with known liver disease, kidney dysfunction, hematologic problems (e.g.
 anemia)

 4. Patients with or suspected allergy to Senna alata extract

 The participation of the subjects were completely voluntary. Participants were allowed to
 withdraw from the study at anytime and for any reason without prejudice to their subsequent
 medical treatment.