Final Mini-Cat

Mini Cat 2 summer 2019

PICO Search Assignment Worksheet                    Name__Kiran______________

 

 

Clinical Question:

 

20 y/o female with Vitamin D deficiency presents to the office with c/o progressive hair loss over the past several months. Patient is not taking any supplementation currently. Patient wants to know if Vitamin D Deficiency causes alopecia.

 

Search Question:

 

Do patient’s with alopecia have decreased Vitamin D levels, when compared to patients without alopecia?

 

PICO search terms:

 

P I C O
Alopecia Vitamin D No Vitamin D Deficiency Serum Vitamin D levels
Alopecia areata Vitamin D deficiency Normal Vitamin D levels serum 25(OH)D concentration
Hair loss Low serum Vitamin D
Hair thinning

 

 

Search tools and strategy used:

 

Database Terms Filter Articles
PubMed Alopecia, Vitamin D Full text, 5 years, Humans 51
PubMed Alopecia Vitamin D deficiency, Serum Vitamin D levels Full text, 5 years, Humans, Review 2
PubMed Hair thinning, Vitamin D deficiency, Serum Vitamin D levels Full text, 5 years, Humans 10
PubMed Hair thinning, Vitamin D Deficiency, Serum Vitamin D levels Full text, 5 years, Humans, Review 2
Cochrane Alopecia, Vitamin D None 21
Trip Database Alopecia, Vitamin D Review 1

Explain how you narrow your choices to the few selected articles.

Based off of the abstract found in the Cochrane search, none of the articles answered the clinical question, majority of the articles focused on other illnesses other than alopecia, with Vitamin D supplementation. Trip Database did not provide an appropriate review for the topic either, and many of the clinical trials that were included in TRIP was also found on PubMed. My first search on PubMed was for a systemic review, because there were only two returns, I chose the review that best answered my question. Once I removed the review filter, I had many more options to choose from. I read through many of the abstracts and if the abstract answered the clinical question and had a decent population size, I chose it to include in the Mini-Cat.

 

The reason why I chose my first article is because it answers my clinical question directly, comparing the level of Vitamin D in patients with Alopecia Areata to a control group. This article also tries to make an association between Alopecia Areata and Vitamin D deficiency, a question that my patient is particularly interested in. Even though I understood that the population size was underwhelming, because of the other factors in this article, I decided to analyze this study further.

 

The second article focused on a pediatric population, which even though it does not correspond to my patient, it is still valuable information considering that my patient has been Vitamin D Deficient for a few years before she became an adult. The positive aspect of this article is that if there is conclusion that is made by the end of this search topic, and if all conclusions are similar, it could be applied to the general population, as well as the pediatric population, and not just be limited to the adult population.

 

The third article that I chose was a systemic review and a meta-analysis. This article has the highest level of evidence and included 14 studies with a total of 2039 participants. This systemic review was also done a little over a year ago, making this article fairly recent and quite appropriate for my clinical scenario. The conclusion of this article made clear associations between the factors that I was focused on and also gave recommendations of supplementations for those patients that have prevalence of both factors.

 

The fourth article that I decided to included, was interesting because it included a factor that I did not necessary see as relevant, vitiligo. The main purpose of this study, was to compare the vitamin D deficiency prevalence between the patients that have Alopecia Areata to those who have vitiligo. Even though the vitiligo factor was unnecessary, this article still answered my clinical question, making it appropriate to further analyze. Both groups of patients were compared to a control group that did not have any medical complications.

Results found:

 

CITATION Gade, V. K., Mony, A., Munisamy, M., Chandrashekar, L., & Rajappa, M. (2018, June 04). An investigation of vitamin D status in alopecia areata. Retrieved from https://link.springer.com/article/10.1007/s10238-018-0511-8
ABSTRACT Abstract

Alopecia areata (AA) is a type of non-scarring, recurrent patchy loss of hair in hair-bearing areas and is mostly of autoimmune origin. Previous studies have suggested that some autoimmune diseases were found to be associated with vitamin D deficiency. The current study was designed to assess the levels of serum 25-hydroxy vitamin D and C-reactive protein in AA, as compared with controls and to further identify the association between vitamin D levels and disease severity in patients with AA. This cross-sectional study included 45 patients with AA and 45 healthy volunteers. Clinical and anthropometric parameters were recorded, according to a pre-designed proforma. Serum 25-hydroxy vitamin D and high-sensitivity C-reactive protein were estimated using ELISA kits. The severity of AA was determined using Severity of Alopecia Tool (SALT) score. We observed a significant rise in systemic inflammation as seen by elevated high-sensitive C-reactive protein levels and lowered 25-hydroxy vitamin D levels in patients with alopecia areata, compared to controls (p = 0.001). The levels of 25-hydroxy vitamin D showed a significant negative correlation with disease severity, while hs-CRP levels showed a significant positive correlation with disease severity (ρ = − 0.714, p = 0.001 and ρ = 0.818, p = 0.001). Our results suggest significant systemic inflammation and vitamin D deficiency in alopecia areata, more so with increasing disease severity. This gains particular importance in the treatment of alopecia areata in future, as supplementing vitamin D to AA patients would result in reducing the disease severity and inducing remission.

 

LINK/PDF https://link-springer-com.york.ezproxy.cuny.edu/article/10.1007/s10238-018-0511-8

 

 

CITATION Unal, M., & Gonulalan, G. (2017). Serum vitamin D level is related to disease severity in pediatric alopecia areata. Journal of Cosmetic Dermatology,17(1), 101-104. doi:10.1111/jocd.12352
ABSTRACT

Summary

Background

Alopecia areata (AA) is the most common cause of inflammatory hair loss. AA is considered an autoimmune disease and occurs with various autoimmune disorders. Recent studies have revealed connection between autoimmune diseases and vitamin D deficiency.

Objectives

In this study, we investigated vitamin D status in AA and its relationship with disease severity, number of patches, and disease duration.

Methods

This study included 20 pediatric patients with AA and 34 pediatric healthy controls. The serum vitamin D levels were evaluated.

Results

The mean serum 25(OH)D concentration of patients was 15.47±7.66 ng/mL and of control group was 11.09±10.53 ng/mL. There was no statistically significant difference between two groups (P: .084). Vitamin D concentration had significantly and negatively correlated with SALT score (P<.001 and r: −.831), number of patch (P<.001 and r: −.989), and disease duration (P<.001 and r: −.997).

Conclusion

Vitamin D deficiency is not the only etiologic factor in AA pathogenesis, but in the presence of other etiological factors, this deficiency can aggravate AA severity, and thus, vitamin D supplementation may be beneficial in treatment of pediatric AA

 

LINK/PDF https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/10.1111/jocd.12352

 

 

CITATION Lee, S., Kim, B., Lee, C., & Lee, W. (2018). Increased prevalence of vitamin D deficiency in patients with alopecia areata: A systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology,32(7), 1214-1221. doi:10.1111/jdv.14987
ABSTRACT

Abstract

Background

Alopecia areata (AA) is a hair follicle‐specific autoimmune disorder. Vitamin D deficiency has been associated with various autoimmune disorders for its immunomodulatory effects. However, in previous studies, there had been inconsistent association found between AA and vitamin D deficiency.

Objective

To demonstrate the differences of the mean serum 25‐hydroxyvitamin D level and prevalence of vitamin D deficiency between AA patients and non‐AA population.

Methods

A systematic review and meta‐analysis of observational studies on AA and serum vitamin D levels and/or prevalence of vitamin D deficiency was performed searching MEDLINE, Cochrane, Web of Science and Google Scholar databases.

Results

In all, 14 studies including a total of 1255 AA subjects and 784 non‐AA control were analysed. The mean serum 25‐hydroxyvitamin D level was significantly lower in AA subjects (−8.52 ng/dL; 95% confidential interval; −5.50 to −11.53). The AA subjects had higher odds of vitamin D deficiency (odds ratio of 3.89; 2.02 to 7.49, mean prevalence of 73.8%; 59.1 to 84.6%). However, it was difficult to find clear correlation between serum 25‐hydroxyvitamin D level and extent of hair loss in AA subjects.

Conclusion

The AA subjects had lower serum 25‐hydroxyvitamin D level, and vitamin D deficiency was highly prevalent compared to non‐AA controls. Hence, vitamin D deficiency should be assessed in AA patients. Furthermore, nutritional supplementation of vitamin D or topical vitamin D analogues can be considered for AA patients with vitamin D deficiency. The limitation of this study is the highly heterogeneity of the included studies.

 

LINK/PDF https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/10.1111/jdv.14987

 

 

 

CITATION Cerman, A. A., Solak, S. S., & Altunay, I. K. (2014). Vitamin D deficiency in alopecia areata. British Journal of Dermatology,170(6), 1299-1304. doi:10.1111/bjd.12980
ABSTRACT

Summary

Background

Alopecia areata (AA) is a T cell‐mediated autoimmune disease that causes inflammation around anagen‐stage hair follicles. Insufficient levels of vitamin D have been implicated in a variety of autoimmune diseases. Previous reports have described the effects of vitamin D on hair follicles.

Objectives

To evaluate the status of vitamin D in patients with AA, and the relationship between vitamin D levels and disease severity.

Methods

A cross‐sectional study of 86 patients with AA, 44 patients with vitiligo and 58 healthy controls was conducted. The serum vitamin D levels of the study group were determined by liquid chromatography/tandem mass spectrometry.

Results

Serum 25‐hydroxyvitamin D [25(OH)D] levels in patients with AA were significantly lower than those of the patients with vitiligo and the healthy controls (= 0·001 and < 0·001, respectively). The prevalence of 25(OH)D deficiency was significantly higher in patients with AA (91%) compared with patients with vitiligo (71%) and healthy controls (33%) (= 0·003 and < 0·001, respectively). Furthermore, a significant inverse correlation was found between disease severity and serum 25(OH)D level in patients with AA (r = −0·409; < 0·001).

Conclusions

Deficient serum 25(OH)D levels are present in patients with AA and inversely correlate with disease severity. Accordingly, screening patients with AA for vitamin D deficiencies seems to be of value for the possibility of supplementing these patients with vitamin D.

 

LINK/PDF https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/10.1111/bjd.12980

 

 

 

 

 

 

 

 

 

 

Author (Date) Level Of Evidence Sample/ Setting

(# of subjects/ studies, cohort definition etc.)

Outcomes(s) studied Key Findings Limitations and Biases
Gade (2018) Cross-Sectional ·       45 patients with Alopecia areata

·       45 healthy volunteers

·       Study held in South India

·       All subjects were studied during the season of winter to avoid seasonal variations in 25-hydroxy vitamin D concentrations

·       Five milliliters of blood was drawn from each participant

 

Primary outcomes:

·       levels of serum 25- hydroxy vitamin D

·       Levels of   CRP using the ELISA kits.

·       Severity of Alopecia was determined by the SALT score

·       This article points out that this topic is controversial, with many patients without Alopacia having Vitamin D deficiency.

·       This study did not include a one-point case control study, meaning the affects of Vitamin D supplementation was not accessed in these patients

·       Vitamin D and hs-CRP is strongly correlated with disease severity, meaning Vitamin D deficiency is a significant risk factor for alopecia

·       One of the major limitations that the study acknowledged was that they did not study the effect of Vitamine D supplementations to the patients with Alopecia Areata, if this was done, a better causative affect could have been concluded

·       Because this study was conducted in India, due to environmental and cultural differences, nutritional factors might have also affected people invovled in this study

Unal, M., & Gonulalan, G. (2017) Case-Control ·       20 Pediatric Patients with Alopecia Areata, all had multiple patches

·       34 pediatric healthy controls

·       All paitents were studied within a five month period to avoid seasonal variations in Vitamin D levels

·       All participants were from Konya, Turkey and had a BMI of less than 25

Primary outcomes:

·       levels of serum 25- hydroxy vitamin D

·       Severity of Alopecia was determined by the SALT score

·       Data was analyzed by the SPSS 24.0 computer system

·       This study revealed a significant inverse correlation of serum Vitamin D level with SALT score and alopecic patch number, indicating that vitamin D levels are associated with disease severity or extent of hair loss.

·       Serum Vitamin D levels are inversely correlated with disease duration, which may be due to that lower vitamin D levels may prevent spontaneous regression of AA or cause resistance to treatment, resulting in a longer disease duration

·       There may have been the presence of other etiological factors, which may have gone undetected, and Vitamin D deficiency just exacerbated the disease severity

·       Because this is a pediatric population; there is limited about of infromation, as well as participants that are willing delve deeper into this topic, causing association between alopecia areata and vitamin D deficiency not well understood

·       This is also the first study comparing serum vitamin D levels in pediatric patients with Alopecia and healthy controls, meaning there is little to no evidence to compare these results to.

·       Like other studies, this one also recomendes supplementing patients with Vitamin D to see improvement of the Alopecia, however, no clinical trial was conducted to prove these results.

Lee, S., Kim, B., Lee, C., & Lee, W. (2018) Systemic Review ·       Search included Medline, Cochrane, Web of Science and Google Scholar databases

·       A total of 14 studies, all of which were case-control

·       A total of 1255 patients with Alopecia Aretara

·       A total of 784 healthy control

Primary outcome:

·       Serum level of 25-hydrocyvitamin D

·       Prevalence of vitamin D defincency in the Alopecia Areata patients and non-AA controls

Additional outcomes:

·       Any changes in serum 25 (OH) D level according to the severity of AA

·       Vitamin D deficiency was found in 609 of the 1133 subjects in the AA group and in 200 of the 658 subjects in the control group. This result suggests the close association between AA and vitamin D deficiency.

·       The interpretation of an association between Vitamin D deficiency and Alopecia could not be applied universally because one case control study in the pediatric population showed evidence of no difference between the two groups

·       A major limitation of this study is that the study population and settings of the included studies were highly heterogeneous. Because serum 25(OH)D levels can be influenced by various factors including geographic features, season, ethnicity, skin color and lifestyle, care should be taken when interpreting results unifying these conditions.

·       In addition, all the studies included had a cross‐sectional nature and therefore did not show any time‐series relationships and casualty between the severity and course of the disease and serum 25(OH)D levels.

Cerman, A. A., Solak, S. S., & Altunay, I. K. (2014) Cross-Sectional ·       86 patients with Alopecia Araeta, 51 patients had multiple patches; 35 had single patches

·       44 patients with Vitiligo

·       58 healthy controls, much of whom were volunteer staff

·       All patients were in Instanbul, Turkey

·       All patients were studied during a 5 month period to avoid seasonal variations in Vitamin D

Primary Outcome:

·       levels of serum 25- hydroxy vitamin D

·       Severity of Alopecia was determined by the SALT score

·       BMI

 

 

·       The mean serum 25 (OH) D concentration of patients with Alopecia was significantly lower than that of patients with vitiligo and that of the healthy controls

·       A significant negative correlation between SALT score and serum 25(OH)D level was found in the patients with alopecia

·       The mean 25(OH)D levels were found to be significantly lower in women with Alopecia than with men with Alopecia

·       No significant correlations was seen between age and 25(OH)D levels in the study group

·       This is the first study that was done that compared vitamin D levels in patients with Alopecia with healthy controls as well as chronic autoimmune skin disease as a positive control. Because of this, there is limited evidence to compared these findings to

·       There were no patients with severe Alopecia

·       Exposure to sunlight, dietary vitamin D intake and inflammatory cytokine levels were not assessed.

 

 

 

Conclusions:

In the first article, which is a case-control study, it was concluded that even though the exact mechanism is unknown, there is in fact an association between Alopecia Araeta and Vitamin D deficiency. The article states that the probable pathogenesis of Alopecia could be attributed to autoimmunity and inflammation. Earlier studies have shown that vitamin D inhibits expression of pro-inflammatory cytokines. This article also acknowledges that previous studies on this topic have had highly controversial results. As mentioned in the limitations, this study was conducted in South India, were the prevalence of Vitamin D deficiency is high. However, even with all these factors included, the study overall suggest significant systemic inflammation and Vitamin D defiency in Alopecia Araeta. Because of this association, treating patients with Vitamin D supplementation could lead to a decrease in the severity of Alopecia Areta.

The second article, even though addressing the pediatric population, gives valuable information about the association between Vitamin D deficiency and Alopecia Areata. This article addresses that Vitamin D plays a role in inhibiting the section of proinflammatory responses, as mentioned in the first article. It stresses the association between Vitamin D defincecy and other auto immune responses, such as RA, SLE, psoriasis, vitiligo, MS, and IBD. ___ also wanted to point out that previous studies, even though they have shown a decrease in serum Vitamin D levels in patients with Alopecia Areata, there is still no correlations between concentrations of vitamin D and hair loss. Once again, the main finding in this study included that even though there was a decrease serum level of Vitamin D in patients with Alopecia Areata, the differenct was not significant between the two groups.

The third article which was a systemic review/ metanalysis, concluded that patients with alopecia areata had a lower serum level by 8.52 ng/dL when compared to the control groups. Because Vitamin D deficiency was found in 609 of the 1133 participants, with alopecia areata and 200 of the 658 heathy patients, a strong association between alopecia and Vitamin D deficiency was made. This review also mentioned that vitamin D deficiency is closely associated with increase susceptibility to infection, fatigue, bone loss and mood instability. As other studies have also mentioned, Vitamin D deficnecy has been associated with other autoimmune disease, when compared to the healthy population. One of the largest limitations to this systemic review was the heterogenicity of the studies involved, considering that serum Vitamin D levels are dependent on a variety of factors including geographic features, season, ethnicity, skin color and lifestyle.

The fourth article, like the majority of the previous articles, was also a case control. This case control was of the few that not only compared vitamin D levels to the healthy population, but also patients that had vitiligo. This study found that patients with alopecia areata had a lower Vitamin D serum level compared to patients with vitiligo. Patients with vitiligo were also found to have a lower serum vitamin D level when compared to the healthy population, but still higher than the alopecia group. With this result obtained, an association between alopecia areata and Vitamin D deficiency was concluded, however it could not be concluded that vitiligo and vitamin D deficiency have an association.

 

 

 

Clinical Bottom Line:

 

There is an overwhelming amount of evidence that suggest that there is an association between Alopecia Areata and Vitamin D deficiency. This conclusion has been solidified in the adult population, but can not be generalized to the pediatric population, due to previous studies that show no correlation nor association between Vitamin D deficiency and Alopecia Areata, in children under 18 years of age. Because my patient is a young adult, and states that she has had Vitamin D deficiency for the past several years, there is a possibility that her vitamin D deficiency might be exacerbating her alopecia. Because the patient is not on any Vitamin D supplementation, I would recommend this patient to start taking Vitamin D supplementation and see if she see’s a difference in hair loss. I would also re-check her blood work if the vitamin D supplementation does not affect her alopecia, looking for any other auto immune markers, possibly indicating other autoimmune diseases.