INTRODUCTION: Pyoderma gangrenosum is a rare neutrophilic dermatoses in children of unknown etiology. Its occurrence may be associated with a systemic condition. In most cases, diagnosis is late and treatment is sometimes refractory to conventional therapies especially if the underlying disorder is undetected. CASE REPORT: A 3-year-old Filipino male presented with a one-year history of extensive ulcers over the nape, chest, back and lower extremities which started as a solitary painful pustule over the right gluteal area. Central healing was observed with cribriform scarring. Patient was previously treated as a case of skin infection without success. Significant laboratory findings showed severe anemia, neutrophilia, increased ferritin and increased ESR. Initial hemoglobin electrophoresis showed normal profile with mild microcytic anemia. Bacterial culture and ANA (anti-nuclear antigen) were negative. A course of oral prednisone (1-2mkd) and dapsone (2mkd) were given for a month with no improvement of the lesions. Folic acid alone was started at 5mg per day for anemia. After 2 weeks, lesions significantly improved. Three years later, upon repeat hemoglobin electrophoresis test, patient was diagnosed with alpha-thalassemia trait. Folic acid was given as mainstay therapy. Lesions healed with characteristic cribriform scarring. CONCLUSION: This is a rare case of a Filipino child who initially manifested with pyoderma gangrenosum and eventually diagnosed with alpha-thalassemia trait. Due to serious cosmetic sequelae of pyoderma gangrenosum, it is important to find and treat the underlying systemic disorder to stop progression of this debilitating and disfiguring dermatosis
Pyoderma Gangrenosum ; alpha-Thalassemia ; Ulcer ; beta-Thalassemia ; Family

Background: Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. Objectives: To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review. Methods: We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www. isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. Results: We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. Conclusion It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.
Azoles ; Tinea Versicolor

BACKGROUND AMSTAR 2 enables a more detailed assessment of systematic reviews and includes non-randomised studies of healthcare interventions, compared to its earlier version, AMSTAR. We validated AMSTAR 2 in a group of systematic reviews in dermatology in the Philippines. METHODS We used a cohort of systematic reviews (SRs) in dermatology from the Philippine that were previously described in Part 1 of this 2-part series. The SRs included clinical trials on any intervention for the treatment or prevention of a dermatologic disease or for maintenance of healthy skin, hair or nails. Two reviewers independently extracted data and used AMSTAR 2 to appraise the methodological quality of each included SR. We determined construct validity by comparing the number of critical flaws between a set of non-Cochrane and matched Cochrane reviews, using Wilcoxon rank sum test. We tested for interrater reliability of the AMSTAR 2 tool using Gwet’s AC1 statistic. RESULTS: We included 20 non-Cochrane systematic reviews in dermatology by Philippine-based authors, and a set of 20 reviews from the Cochrane skin group, matched by year and randomly chosen. Construct validity testing showed a significantly greater number of AMSTAR 2 critical flaws (median 4.5 vs 0.0; z=3.64; P=0.000) and non-critical weaknesses (5 vs 2.0; z-score=3.10; P-value=0.001) by non-Cochrane reviews compared to a matched set of Cochrane skin group reviews. There was good interrater reliability (average Gwet’s AC1 statistic = 0.87) with the lowest agreement (0.62) for discussion of heterogeneity (item 14), and the highest agreement (0.97) for study selection criteria (item 3). CONCLUSION The AMSTAR 2 was a valid and reliable tool for assessing systematic reviews using a cohort of reviews by dermatology reviews, both non-Cochrane and Cochrane. Further validation of the AMSTAR 2 is needed to determine if it can be applied to a wide variety of systematic reviews.

BACKGROUND: Quality systematic reviews (SRs) are essential in the practice of evidence-based dermatology. We assessed the methodologic quality of SRs in dermatology from the Philippines. METHODS: We searched databases (MEDLINE, CDSR, PROSPERO, HERDIN; from inception until June 30, 2019), and secondary sources. We included SRs, authored by Filipino primary authors, which included clinical trials on any intervention for the treatment or prevention of a dermatologic disease or for maintenance of healthy skin, hair or nails. Two reviewers independently extracted data and appraised the methodological quality of each included SR using the AMSTAR 2. The 16-item AMSTAR 2 has 7 critical items and 9 non-critical items. The number of critical items mainly determine the overall confidence in the results of the review. Descriptive analysis using means and standard deviation for continuous data, and frequency and percentage distribution for categorical data were employed. RESULTS: Twenty SRs were included in this review, and were mostly published in the 2010s. Majority of SRs had three authors, who belonged to a single institution, with at least one dermatologist. The most common topic was infections and both oral and topical interventions were used. Majority had 5 included studies in the SRs, with a median number of 425 participants. The median number of critical flaws in the included SRs was 4.5, and non-critical flaws, 5. Overall confidence was critically low in majority (19/20 ) of included reviews, with only one review rated as low. CONCLUSION: The methodologic quality of the dermatology SRs from the Philippines based on the AMSTAR 2 tool was poor with a rating of critically low in majority. There is a need to improve quality of conduct and reporting through dissemination of the reporting guidelines such as the PRISMA
Humans ; Nails ; Philippines ; Dermatologists ; Dermatology ; Data Management ; Data Collection ; Publications ; Maintenance ; Reference Standards

Chromoblastomycosis is an endemic mycoses which has been misdiagnosed or underdiagnosed in the past. This may be due to the clinicopathologic characteristics that it shares with other neglected tropical diseases such as leprosy and cutaneous tuberculosis. Correlating clinical findings with histopathologic cues will lead clinicians to correct diagnosis and subsequent treatment success.
Chromoblastomycosis ; Invasive Fungal Infections ; Itraconazole

Background: Herbal medicine is a growing and innovative field in Philippine dermatology. There is a need to assess the quality of reporting of published herbal randomized controlled trials (RCTs) in dermatology since these will serve to guide rational development and use of medicinal plants in the Philippines. Objective: The study aimed to assess the quality of reporting of published herbal RCTs in dermatology from the Philippines based on the hCONSORT checklist. Methods: We searched MEDLINE, CENTRAL, HERDIN (from inception to 20 September 2018), and other secondary sources for published randomized controlled trials that used any herbal preparation as intervention for the treatment or prevention of a dermatologic disease or for maintenance of healthy skin, hair, or nails. We determined the percentage of reported items based from the hCONSORT checklist. Results: We included 41 trials, majority of which were on infections, infestations, and bites (66%). The three most common families of herbs used were Fabaceae/Leguminosae (22%) (Gliricidia sepium (Jacq.) Walp. [kakawati]; Senna alata (L.) Roxb. / Cassia alata (L.) [akapulko]); Arecaceae (12%) (Cocos nucifera L. [coconut]); and Myrtaceae (12%) (Eucalyptus sp [eucalyptus], Psidium guajava L.[guava], and Melaleuca alternifolia (Maiden & Betche) Cheel [tea tree]). Most of the trials (27/41, 66%) were conducted in accredited dermatology training programs of the Philippine Dermatological Society. Only 11 trials (27%) were published in PubMED-indexed journals. More than half of articles were published after the CONSORT publication in 2006 (59%). The mean percentage of reported hCONSORT checklist items in included studies was 39.6% (SD 9.9), with only seven studies reporting more than 50% of the hCONSORT checklist items. Conclusion Published herbal RCTs in dermatology from the Philippines are poorly reported based on the hCONSORT checklist. There is a need for dissemination of the hCONSORT to local researchers and journal editors to ensure thorough and quality reporting.
Herbal

Background: Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by Malassezia furfur, a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking. Objectives: To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review. Methods: We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www. isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes. Results: We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I2=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment. Conclusion It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.
Azoles ; Tinea Versicolor

Background and Objective: Scabies is the second most common cause of disability due to skin disease in the Philippines. However, there were no cited studies in Global Burden of Disease 2019 and the disability-adjusted life years (DALY) computations were most likely based on statistical modelling. The Philippine Department of Health has embarked on a program to estimate the disease burden of priority diseases in the country, which include scabies. The last nationwide prevalence survey was 23 years ago. This systematic review aimed to estimate the prevalence or incidence of scabies in the Philippines. Methods: We searched PubMed, Scopus, Herdin, and Philippine Health Research Registry (search date October 2022) for studies on prevalence/incidence (including systematic reviews, cross-sectional studies, cohort studies, case series, registry or census studies) of patients diagnosed with scabies in the Philippines. We excluded narrative reviews, commentaries, and conference proceedings or abstracts. Two reviewers independently screened titles and abstracts, assessed full text reports for eligibility, appraised the quality of included studies, and collected data using a pretested data extraction form. We did not pool studies due to clinical heterogeneity but plotted the individual studies in a forest plot with prevalence estimates and confidence intervals. We reported the median and interquartile range for entire group or relevant subgroups (age, setting) of studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence. Results: We included nine studies (N=79,065). Most were clinic-based prevalence studies, retrospective chart reviews, conducted in dermatology outpatient clinics, Metro Manila area, and on pediatric populations. Prevalence of scabies was moderate (i.e., between 2 and 10%), ranging from 2.75% (national prevalence survey) to 6.8% (communitybased review), to high (> 10%) among pediatric patients in clinic-based retrospective chart reviews (29 to 36%) and institution-based surveys (39.0% to 45%), and a tertiary government university training hospital dermatology clinic (22.9%). The most affected age group was from 0 to 14 y/o, while males tended to have a higher prevalence than females. The cooler month of January had higher prevalence than the hotter month of June in one study. Conclusion Scabies is common in the Philippines, especially among children and elderly in institutional settings, and during the month of January. There is a need to do a national prevalence survey to identify high-risk areas and to monitor the prevalence of scabies, especially in crowded settings and vulnerable populations. This information can be used for estimating the burden of disease for scabies and guide appropriate health resource allocation.
Scabies ; Philippines ; Epidemiology ; Prevalence ; Incidence

INTRODUCTION: Oral ivermectin is an approved first-line option to topical permethrin in Europe and Japan for the treatment of classic scabies, while combination oral ivermectin and topical permethrin is used in clinical practice for extensive or recurrent cases. There is unclear evidence on comparative efficacy and safety.

OBJECTIVES: To review the evidence on efficacy and safety of oral ivermectin versus topical permethrin or its combination in the treatment of classic scabies.

METHODS: We searched PubMed from January 1, 2016 up to August 7, 2021 for systematic reviews that included RCTs comparing oral ivermectin versus topical permethrin or its combination in the clinical treatment of scabies. We described the characteristics of included studies, assessed reporting quality, and summarized results and conclusion.

RESULTS: We included five systematic reviews. Permethrin did not differ from oral ivermectin in cure rate at the 3 to 6-week time point but had an earlier cure at 1-2 weeks. Adverse effects did not significantly diff er and were few, mild, and transient with both treatments. The evidence ranged widely from low to high certainty and mainly came from three moderate-to-high quality systematic reviews. Combination oral ivermectin and topical permethrin was ranked higher in efficacy but lower in safety compared to either drug alone in one moderate validity network meta-analysis.

CONCLUSION: There is varying certainty of evidence suggesting comparable efficacy and safety of oral ivermectin versus topical permethrin. Limited evidence suggest higher efficacy and lower safety of combination oral ivermectin and topical permethrin compared to either drug alone. An updated systematic review and network meta-analysis is warranted.

KEYWORDS: scabies, ivermectin, permethrin, effectiveness, efficacy, safety

Background and Objective: Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies. Methods: We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty. Results: Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve. Conclusion Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.
Scabies ; Ivermectin ; Permethrin ; Cost-Benefit Analysis