Relationship of Whole Blood Zinc Levels to Acne Severity
Condition: Acne Vulgaris
MeSH terms: Acne Vulgaris
Study type: Observational

Summary: 
      Acne Vulgaris is one of the most common dermatologic diagnoses in the world. A number of
      studies have been conducted comparing serum zinc levels with acne vulgaris; however, no
      studies have yet been done in the Philippine setting.

      The objective of this study is to determine the relationship between whole blood zinc levels
      and the severity of acne vulgaris in Filipino patients and normal controls who are 18-25
      years old.
    

Detailed description: 
      Acne Vulgaris is a disorder of the pilosebaceous unit characterized by formation of
      comedones, papules, pustules, inflamed nodules, and cysts.1 Most common predilection sites
      are those with hormonally sensitive sebaceous glands such as the face, neck, chest, upper
      back and upper arms. Acne can persist for years and result in disfigurement and permanent
      scarring. It can cause serious adverse effects on psychosocial development, resulting in
      emotional problems, withdrawal from society, and depression. Nearly all adolescents
      experience different severity levels of acne vulgaris, with moderate to severe levels
      affecting around 20% of this population. In the Philippines, high school students were found
      to have a mild impairment of quality of life (QOL) due to acne, regardless of severity.
      Despite the known treatment regimens for acne, people are still suffering from the effects of
      the disease.

      Acne has four main pathogenic contributors: follicular hyperkeratinization, increased sebum
      production, Propionibacterium acnes (P. acnes) within the follicle, and inflammation. Reports
      show that antibiotic resistance is a growing issue in the treatment regimen of acne vulgaris,
      making it less and less suitable for long-term treatment. Other options that can be
      substitutes or adjuncts to treatment may be useful in this condition.

      Zinc is an essential element for normal epithelial differentiation and for normal
      development. It has also been shown to have antioxidant properties. At present, there is
      paucity of data regarding the role of zinc levels in the development or severity of acne
      vulgaris. Also, data on favorable effects of dietary factors such as zinc, omega-3 fatty
      acids, antioxidants, vitamin A, and dietary fiber on acne vulgaris are limited specially in
      the Philippines.

      This study will be conducted to measure the whole blood zinc levels in patients with acne
      vulgaris and compare it with healthy controls. This aims to determine the relationship
      between whole blood zinc levels and disease severity in Filipino patients with acne vulgaris
      in order to bring new insight to guide further studies regarding zinc's role in the
      pathogenesis and possible further treatment of acne vulgaris in the Philippines.

      Significance of the Study:

      While a number of studies have been conducted comparing serum zinc levels with acne vulgaris,
      no previous studies have been done in the Philippine setting that assesses the relationship
      of whole blood zinc levels with the severity of acne. Given that acne vulgaris is one of the
      most common dermatologic diagnoses in the Philippine population, and the increasing
      resistance to antibiotics commonly used to treat acne, studies about other treatment
      modalities for acne vulgaris that do not have resistance factors are timely and significant
      in the country.

      For long-term or maintenance therapy, physicians should consider effectivity, cost, and
      adverse effects. By determining the relationship of whole blood zinc levels to acne severity
      among Filipinos 18-25 years old, this study can be used as evidence for giving zinc
      supplements to Filipino people diagnosed with acne vulgaris if a significant relationship is
      found. Since zinc is more cost-effective and has less adverse effects compared to most
      antibiotics, this may prove helpful for the Filipino patient in terms of safety and economy
      for long-term therapy. Furthermore, this study may also be able to provide more information
      for further studies towards non-antimicrobial treatment regimens for acne vulgaris in the
      Philippines.

      Research Question:

      Is there a relationship between whole blood zinc levels and the severity of acne vulgaris in
      Filipino patients 18-25 years old versus normal controls?

      Null Hypothesis: There is no relationship between whole blood zinc levels and the severity of
      acne vulgaris.

      Alternative Hypothesis: There is a relationship between whole blood zinc levels and the
      severity of acne vulgaris.

      Objectives:

        -  To study the relationship between whole blood zinc levels and the severity of acne
           vulgaris in Filipino patients 18-25 years old and normal controls

        -  To describe the clinical profile of Filipino patients 18-25 years old with acne vulgaris

        -  To determine the whole blood zinc levels of acne patients compared to controls

        -  To determine the relationship of the clinical severity of acne vulgaris to whole blood
           zinc levels

      A cross-sectional comparative study design will be utilized for this study which will be
      conducted from November 2017 to March 2018. The study will be conducted at the Dermatology
      Out-patient Clinic of the East Avenue Medical Center (EAMC).

      STUDY PROCEDURE

        1. The study will be submitted to the Technical Review Board and Institution Ethics and
           Review Board for approval.

        2. In the Dermatology Out-Patient Department of East Avenue Medical Center, patients
           seeking consult for their skin lesions which were diagnosed to be Acne Vulgaris will be
           screened if they meet the inclusion/exclusion criteria.

        3. Informed consent will be obtained for those who are qualified.

        4. Patients will be given proper treatment whether they agree to participate or not. For
           the patients who agree to participate, the investigator will assess the patient's acne
           severity using the Global Acne Grading Scale (GAGS).

        5. Twelve milliliters of blood will be extracted from the patient with proper aseptic
           technique and waste disposal.

        6. Blood sample will be properly stored in three EDTA tubes, labelled, and transported to
           the laboratory for determination of whole blood zinc levels through ashing acid
           digestion- inductively coupled plasma (ICP) using Shimadzu ICPS-7510, an inductively
           coupled plasma emission spectrometer.

             1. Blood samples are viable and stable for 5 days at 15-25 degrees Celsius.

             2. A memorandum of agreement between the principal investigator and Hi-Precision
                Diagnostics, Inc. has been made. Hi-Precision Diagnostics will be providing the
                materials for extraction, picking-up, and transporting the blood sample using a
                special insulated medical specimen bag (Versapak Pathology and Specimen bag) with
                ice packs and thermometer to help maintain the ideal temperature of 15-25 degrees
                Celsius.

             3. Schedule of specimen pick-up is from 8:00 am- 8:00 pm and may be done on an
                as-needed basis. The blood specimens will be stored in the refrigerator immediately
                after extraction.

        7. Results will be obtained by the investigator via the online results portal of the
           laboratory.

        8. Data collected will be tabulated and data analysis will be done.

      PASS 2008 was used for the computation of minimum sample size. Parameters for the computation
      was obtained from previously published studies. For the one-way ANOVA, a minimum of 40
      patients (10 for each acne severity: mild, moderate and severe acne and 10 for controls)
      achieves 95% power to detect differences among the means versus the alternative of equal
      means using an F test with a significance level of 0.05. The size of the variation in the
      means is represented by their standard deviation which is 13.30 mg/dL and the common standard
      deviation within a group is assumed to be 20.00 mg/dL.

      Data will be encoded by the researcher in MS Excel. The excel file will be converted into
      Stata file for further data processing and analysis. Stata SE version 12 will be used for
      both descriptive and inferential statistics. Quantitative variables will be presented as mean
      or median while qualitative variables will be presented as percentages.

      In order to compare the whole blood zinc levels between cases and controls, independent
      T-test will be used. ANOVA will be used to compare the whole blood zinc levels by acne
      severity. Multiple linear regression analysis will then be performed in order to determine
      the association of whole blood zinc levels with acne severity after controlling for the
      effects of significant confounding variables. All p values ≤ 0.05 will be considered as
      significant.

      The correlation of whole blood zinc levels with severity of acne vulgaris in Filipino
      patients may help clinicians recommend more detailed dietary advice and add non-antibiotic
      supplements to their current treatment of acne vulgaris. The results of the study can serve
      as a guide for further studies related to whole blood zinc and its role in the pathogenesis
      of acne vulgaris in Filipino patients.
    

Intervention name(s): Whole blood zinc level
Intervention type(s): Diagnostic Test
Intervention description(s): whole blood zinc levels determined through ashing acid digestion-inductively coupled plasma (ICP) using Shimadzu ICPS-7510, an inductively coupled plasma emission spectrometer.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The subjects of the study included patients clinically diagnosed with acne vulgaris and
        healthy controls, aged 18-25 years of age.
      
Keywords: Acne Vulgaris; Zinc in blood; Global Acne Grading System