Oral Vitamin D Treatment in Patients with Telogen Effluvium: Clinical and Dermoscopic Evaluation

ABSTRACT

Background:

Telogen effluvium (TE) is the most common hair loss. Vitamin D is related to hair and skin diseases due to its immunomodulatory and anti-inflammatory effects.

Objective:

To investigate Vitamin D serum level role in TE pathogenesis.

Patients and Methods:

Forty females with TE were collected and twenty age- and sex-matched healthy individuals as controls. Serum 25(OH) Vitamin D level was estimated prior and 3 months after oral Vitamin D.

Results:

The mean serum 25(OH) Vitamin D levels were significantly lower in TE patients than controls (13.31 ± 5.8 ng/ml vs. 33.61 ± 8.16 ng/ml) respectively, P < 0.001. The mean serum 25(OH) Vitamin D levels before treatment in acute TE was 12.31 ± 6.88 ng/ml, compared to 10.6 ± 3.9 ng/ml in chronic TE without a significant difference, (P = 0.544). The mean serum 25(OH) Vitamin D levels in TE group after 3 months oral Vitamin D therapy were 38.4 ± 15.22 ng/ml with significant increase compared to pretreatment level, (P < 0.001). However, without a significant difference between acute TE (45.4 ± 9.22 ng/ml) and chronic TE (42.1 ± 10.6 ng/ml), (P = 0.711).

Conclusion:

Oral Vitamin D has a promising effect in TE treatment, but the results need to be verified on a larger scale with evidence-based recommendation regarding the exact dose and treatment duration.

INTRODUCTION

Telogen effluvium (TE) is the most common type of acquired, diffuse, nonscarring alopecia that occurs due to an abnormal shift of scalp hair follicles from anagen to telogen, leading to premature shedding of telogen hair.[1]

If hair shedding lasts <6 months so it is acute TE, while if more than 6 months it is considered chronic TE.[2]

Hair follicles are sensitive to hormones, including Vitamin D, which plays a vital role in calcium metabolism, immune system regulation as well as cell growth and differentiation.[3] The active form of Vitamin D, 1,25 dihydroxy Vitamin D3 [1,25(OH)2D3], performs its action by binding to specific Vitamin D receptors (VDRs) in the nuclei of target cells, which function as ligand-inducible transcription factors, regulating Vitamin D-responsive genes.[4]

VDRs are expressed in the outer root sheath, hair follicle bulb, and sebaceous glands in the hair follicle, where they regulate skin biology, as epidermal proliferation, and differentiation. In addition, studies demonstrated that VDRs are important for normal hair cycling, especially anagen initiation.[5,6]

Serum level of Vitamin D is considered a factor in approaching patients with hair loss complaint.[7] It has been suggested that an optimum concentration of Vitamin D3 is essential to delay aging and hair loss.[8,9]

The aim of this work was to investigate the role of serum Vitamin D level in the pathogenesis of TE.

PATIENTS AND METHODS

Patients

This was a case − control study included forty patients with TE who were collected from outpatient clinics of dermatology and venereology, in addition to twenty healthy individuals, age and sex matched served as controls. Ethical Committee approval number (32093/01/18).

Inclusion criteria

Patients presenting with TE based on clinical and dermoscopic findings.

Exclusion criteria

Patients exposed to recent severe hemorrhage, patients who are on calcium modifying drugs or on immunosuppressive drugs, those with thyroid disorders, and drug abusers or patients with other causes of alopecia.

Methods

All patients were subjected to

• Complete history taking including occupation and marital status, onset, course, and duration of the disease. History of chronic diseases, infections, autoimmune diseases, and thyroid disorders. Recent fever, illness, or psychological stress. Family history of female pattern hair loss (FPHL), autoimmune diseases as thyroid disorders. Dietary history and history of drug intake. History of hair care procedures, drug intake. Childbearing history including pregnancy, lactation, and menstruation.

General examination

To rule out any systemic disease, autoimmune disease, thyroid disorders, or signs of hyperandrogenism.

Local examination

Including hair length, color, lusterness, density, diffuse or localized hair loss, and scales. Scalp was examined for signs of inflammation, infection, and scarring; gentle hair pulling test.[10]

Dermoscopic examination

It was performed using polarized-light handheld dermatoscope (Dermalite 2 pro HR; 3Gen LLC, San Juan Capistrano, California, USA) which allows scalp visualization at a 10–fold magnification without an interface solution. Images were obtained using a digital camera (Sony Cybershot DSC–W320/W330, X4 optical zoom, 14.1 megapixels; Sony corporation, Tokyo, Japan) that produced imagery with a magnification of 30-fold through its three-fold optical zoom lens. For every patient, several different images at 10-to-30-fold magnifications were taken and evaluated.

On dermoscopic examination, TE was diagnosed by decreased hair density with the presence of empty follicles, high percentage of follicular units with only one hair, and short re-growing hair. There were no hair shaft diameter variation and peripilar halo excluding androgenic alopecia (AGA).[11]

For both patients and controls

A written informed consent was obtained from all participants in research. Routine investigations including CBC, serum ferritin level, and thyroid functions.

Determination of serum 25(OH) Vitamin D levels

Before treatment

Total 25(OH) Vitamin D was determined according to the enzymatic immunoassay method using a 96 tests Kit obtained from (Calbiotech Inc, Catalog No.: VD220B). The absorbance was measured spectrophotometrically at 450 nm. A standard curve was obtained by plotting the concentration of the standard versus the absorbance. The color intensity would be inversely proportional to serum level of 25 OH Vitamin D [Figure 1].

Figure 1.

Standard curve of 25 OH vitamin D measurement

Treatment of cases

Patients with low Vitamin D3 level received oral treatment in the form of cholecalciferol capsules 5000 IU/day for 3 months.

After treatment: Measurement of serum 25(OH) Vitamin D by the previous method

Evaluation of Vitamin D therapy

1. Clinical assessment:(width of the midline and hair density)

2. Assessment by hair shedding score:[12] The score varies between 1 (minimal shedding) to 6 (copious hair shedding)

3. Assessment by dermoscopy

4. Patients’ satisfaction.

The degree of improvement according to the patient opinion, the patients were asked at the final visit about the overall satisfaction according to whether the patient was slightly, moderately, or highly satisfied.

Statistical analysis

All statistical calculations were done using the computer programs SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 23 for Microsoft Windows.

Descriptive statistics

Qualitative (nonnumerical) data were described in the form of number (frequency) and percentage where quantitative (numerical) data were described in the form of range, median, and standard deviation.

Analytical statistics

Statistical presentation and analysis of the present study were conducted, using the mean, standard deviation, Student t-test, paired t-test, linear correlation coefficient, and analysis of variance tests.

The probability (P) values

• P value > 0.05 nonsignificant

• P value ≤ 0.05 significant

• P value < 0.001 highly significant.

RESULTS

The present study was conducted on forty TE females collected from outpatient clinics of dermatology and venereology department, Tanta University Hospital, in addition to twenty age- and sex-matched healthy individuals served as controls. Serum level of 25(OH) Vitamin D was estimated prior and 3 months after oral Vitamin D supplementation.

Results were as follows

Demographic data of the studied subjects

• The range of age of patients was 1949 years with a mean of 32.3 ± 9.59 years compared to range of 1959 years with a mean of 30.8 ± 7.53 years for controls without significant difference (P = 0.544) Table 1

• The range of duration of TE in patients was 160 months with a mean of 15.73 ± 13.11 months Table 1

• Twelve patients (30%) had acute TE. Twenty-eight patients (70%) suffered from chronic TE Table 2

• The mean age of 25.5 ± 9.32 years in acute TE, the mean age of 36.8 ± 4.88 years in chronic TE with statistically significant difference (P < 0.001) Table 2

• The mean duration of acute TE was 2.5 ± 1.1 months, and the mean duration of chronic TE was 15.33 ± 12.32 months with a statistically significant difference between both groups (P < 0.001) Table 2

• Regarding to family history, thirty patients (75%) had positive family history of disease

• There was significant difference between both patient groups according to the history of the stress, 7 patients (58.3%) with acute TE compared to 20 patients (71.4%) with chronic TE, (P = 0.018).

Table 1.

Demographic data of the studied telogen effluvium patients and controls

Parameters	Groups
	Patients (n=40)	Controls (n=20)	Overall (P)
Age (years)
Mean±SD	32.3±9.59	30.8±7.53	0.544
Range	19-49	19-45
Duration of disease (months)
Mean±SD	15.73±13.11	-	-
Range	1-60	-

Significant – P≤0.05; Nonsignificant – P>0.05. n – Number of cases; SD – Standard deviation

Table 2.

Comparison between acute and chronic telogen effluvium patients as regards age and duration of disease

Parameters	Groups
	Acute TE (n=12)	Chronic TE (n=28)	Overall (P)
Age (years)
Mean±SD	25.5±9.32	36.8±4.88	<0.001***
Range	19-39	32-49
Duration of disease (months)
Mean±SD	2.5±1.1	15.33±12.32	<0.001***
Range	1-6	6-60

***Highly significant – P≤0.001. n – Number of cases; TE – Telogen effluvium; SD – Standard deviation

Regarding to hair shedding score

• The mean score for all TE patients before treatment was 5.50 ± 0.51, after treatment was 1.75 ± 0.84 with statistically significant difference (P = 0.001) Table 3

• The mean score for acute TE patients after treatment was 1.67 ± 0.89 compared to pretreatment score of 5.33 ± 0.49 with statistically significant improvement, (P = 0.001) Table 4

• The mean score for chronic TE patients after treatment was 1.79 ± 0.83 compared to pretreatment score of 5.57 ± 0.50 with statistically significant improvement, (P = 0.001) Table 4.

Table 3.

Hair shedding score for patients before and after 3 months treatment with oral Vitamin D

Hair shedding score	Before treatment	After treatment
Range	5-6	1-3
Mean±SD	5.50±0.51	1.75±0.84
Median	5.5	1.5
z-test	7.901
P	0.001***

***Highly significant – P≤0.001. z – Mann–Whitney test; SD – Standard deviation

Table 4.

Comparison between acute and chronic telogen effluvium patients as regards hair shedding score before and after 3 months treatment with oral Vitamin D

Hair shedding score	Acute TE	Chronic TE	za-test	P
Before treatment
Range	5-6	5-6	0.173	0.247
Mean±SD	5.33±0.49	5.57±0.50
Median	5	6
After treatment
Range	1-3	1-3	0.630	0.673
Mean±SD	1.67±0.89	1.79±0.83
Median	1	2
zb-test	4.304	6.591
P	0.001***	0.001***

***Highly significant – P≤0.001; ^aMann–Whitney test; ^bWilcoxon test. Significant – P≤0.05; Nonsignificant P>0.05. TE – Telogen effluvium; SD – Standard deviation

Regarding to dermoscopic findings

• It was found that among the recruited cases of TE, ten patients (25%) had decreased hair density, empty follicles, high percentage of follicular units with only one hair and short re-growing hair more in the midline, with no signs in other regions. Fifteen patients (37.5%) had these signs more in the temporal region. Fifteen patients (37.5%) had these signs in both regions. There was improvement in these signs after Vitamin D therapy as regard increased hair density, increased number of hairs arising from each follicular unit and decreased number of short re-growing hair Figures 2 and 3.

Figure 2.

Female patient aged 26 years old suffered from telogen effluvium. (a) Before treatment. (b) After 3 months treatment with oral vitamin D. (c) Dermoscopy before treatment, (Dermalite 2 pro HR; 3Gen; polarized mode, ×10). (d) Dermoscopy after 3 months treatment with oral vitamin D, (Dermalite 2 pro HR; 3Gen; polarized mode, ×10)

Figure 3.

Female patient aged 36 years old suffered from telogen effluvium. (a) Before treatment. (b) After 3 months treatment with oral vitamin D. (c) Dermoscopy before treatment, (Dermalite 2 pro HR; 3Gen; polarized mode, ×10). (d) Dermoscopy after 3 months treatment with oral vitamin D, (Dermalite 2 pro HR; 3Gen; polarized mode, ×10)

Regarding the serum level of Vitamin D

• The mean serum level of 25(OH) Vitamin D was significantly lower in TE patients 13.31 ± 5.8 ng/ml compared to controls 33.61 ± 8.16 ng/ml, (P < 0.001), Table 5

• The mean serum level of 25(OH) Vitamin D in all TE patients after 3 months therapy with oral Vitamin D was 38.4 ± 15.22 ng/ml with significant increase in Vitamin D level compared to pretreatment level 13.31 ± 5.8 ng/ml, (P < 0.001) Table 5

• The mean serum level of 25(OH) Vitamin D before treatment in acute TE was 12.31 ± 6.88 ng/ml, compared to 10.6 ± 3.9 ng/ml in chronic TE without a statistically significant difference between both groups (P = 0.544) Table 6

• After treatment, the mean serum level of 25(OH) Vitamin D in acute TE patients was 45.4 ± 9.22 ng/ml, compared to 42.1 ± 10.6 ng/ml in chronic TE patients without a statistically significant difference between both groups, (P = 0.711) Table 6

• The selected cutoff values of serum level of 25(OH) Vitamin D for diagnosing telogen patients from controls was 23 ng/ml with 92.5% sensitivity, 100% specificity, 100% positive predictive value (PPV), 87% negative predictive value (NPV), and 95% accuracy. The area under the curve was 0.994 Figure 4

• As regards correlation between serum level of 25(OH) Vitamin D and other data, Spearman’s correlation test showed negative nonsignificant correlation between serum level of 25(OH) Vitamin D and age, and duration of disease (r= −0.113, P = 0.388, and r=−0.137, P = 0.398, respectively). On the other hand, a significant positive correlation was found between serum level of 25(OH) Vitamin D and family history of disease (r=-0.647, P < 0.001). A significant negative correlation was found between serum level of 25(OH) Vitamin D and stress (r = 0.394, P = 0.002).

Table 5.

Comparison between control and telogen effluvium patients as regards serum level of 25-OH Vitamin D before and after 3 months treatment with oral Vitamin D

Parameters	Groups
	Patients group (n=40)	Control (n=20)	P
Serum level of 25-OH Vitamin D before treatment (ng/ml)
Mean±SD (range)	13.31±5.8 (3.9-25.8)	33.61±8.16 (23.7-51.2)	<0.001***
Serum level of 25-OH Vitamin D after treatment (ng/ml)
Mean±SD (range)	38.4±15.22 (19.1-88)
P	<0.001***

***Highly significant – P≤0.001. n –number of cases; SD – Standard deviation

Table 6.

Comparison between acute and chronic telogen effluvium patients as regards serum level of 25-OH Vitamin D before and after 3 months treatment with oral Vitamin D

Parameters	Groups
	Acute TE (n=12)	Chronic TE (n=28)	P
Serum level of 25-OH Vitamin D before treatment (ng/ml)
Mean±SD (range)	12.31±6.88 (4.55-25.8)	10.6±3.9 (3.9-23.9)	0.544
Serum level of 25-OH Vitamin D after treatment (ng/ml)
Mean±SD (range)	45.4±9.22 (23.5-88)	42.1±10.6 (19.1-76.9)	0.711
P	<0.001***	<0.001***

***Highly significant – P≤0.001. n – Number of cases; TE – Telogen effluvium; SD – Standard deviation

Figure 4.

ROC curve of serum level of 25-OH vitamin D for differentiating patients with telogen effluvium from controls. ROC: Receiver operating characteristic

Regarding to patient satisfaction

• Ten patients (25%) were slightly satisfied, ten patients (25%) were moderately satisfied, and twenty patients (50%) were highly satisfied.

DISCUSSION

Appropriate management of hair loss will not be completed unless different etiologies of hair loss have been identified.[13] Vitamin D is closely related to hair and skin diseases due to its immunomodulatory and anti-inflammatory effects.[14] Vitamin D, through its receptor (VDR), plays a vital role in preserving the hair follicle integrity. While the relevance of VDR has been fully elucidated, the real value of Vitamin D in the hair follicle cycle remains uncertain.[15]

In the current study, the dermoscopic examination of the studied TE patients, showed that 25% of the cases had decreased hair density, empty follicles, and short re-growing hair more in the midline, 37.5% had these signs more in the temporal region and 37.5% had these signs in both regions, with improvement after oral Vitamin D therapy for 3 months.

These findings were in accordance with other literature mentioned that the trichoscopic criteria of TE are short dark re-growing hair, decreased hair density, and presence of empty follicles. It can be easily differentiated from AGA due to absence of hair shaft diameter variation and peripilar halo. It affects the entire scalp unlike AGA.[13,16,17]

As regards the pretreatment 25(OH) Vitamin D serum levels, and effects of therapy, the results of this study showed that the mean serum 25(OH) Vitamin D levels in TE patients were significantly lower than that in controls. P < 0.001, without a statistically significant difference between acute and chronic TE groups, P = 0.544.

Many studies demonstrated that low serum 25 (OH) D is associated with TE,[18] androgenetic FPHL[5,19,20,21] and alopecia areata.[22,23,24]

Naif, 2016[25] detected statistically significant lower mean serum levels of Vitamin D in chronic TE patients compared to control group (7.4 ± 4.9 ng/ml and 18.2 ± 12.4 ng/ml), respectively (P < 0.001).

Moreover, Rasheed et al., 2013[4] observed a significantly lower serum 25 (OH) D levels in TE cases in comparison to control. The lowest level was detected in patients with the most severe hair loss. According to the authors, their results may indicate that Vitamin D participates in TE.

While ÇİFCİ, 2018[14] study results showed nonsignificant lower mean serum levels Vitamin D in chronic TE patients compared to controls (3.42 ± 6.28 ng/ml, 14.62 ± 6.56 ng/ml), respectively, (P = 0.09).

Surit et al.[26] study did not show statistically significant difference in the serum Vitamin D levels between patients of chronic TE (17.41 ± 11.3) and controls (17.63 ± 8.57), (P = 0.455).

It was found that Vitamin D regulates hair follicle cycles, especially anagen initiation. Hence, a shorter life span of hair follicles is associated with its deficiency.[9]

Exposure to UV radiation in the UVB spectrum (290320 nm) converts 7-dehydrocholesterol to Vitamin D3in the skin. Vitamin D is found in healthy hair follicle on the contrary to unhealthy one.[27]

Vitamin D is a precursor to the hair growth cycle.[28] It helps to reduce stress and depression related to hair loss.[29]

Furthermore, extensive studies on animal models showed that VDR plays a key role in the cycle of the hair follicle, especially in the anagen phase. It has been shown that 1.25 (OH) Vitamin D, VDR, and β-catenin are important stimulators for the differentiation of hair follicle.[3,30] Expression of VDRs in keratinocytes is necessary for maintenance of the normal hair cycle in both the late anagen and catagen stages, there is an increase in VDR expression, which is associated with decreased proliferation and increased differentiation of keratinocytes. These changes are thought to promote the progression of the hair cycle.[31]

On the contrary to our results, Mohammad et al., in 2017[32] and Karadağ et al. in 2011[33] published that the levels of serum Vitamin D were significantly higher in patients with TE than in control group. Mohammed et al.[32] explained their results as it may be attributed to small sample size (30 TE cases and 30 controls). While Karadağ et al.[33] explained that the increase in Vitamin D level might not be the cause but a secondary response to TE as the telogen hair follicles do not show melanin synthesis in their undifferentiated melanocytes/melanoblasts, which may increase exposure to ultraviolet light and Vitamin D synthesis in the skin.[34]

According to the authors, the observed increased serum 25(OH) Vitamin D levels in TE might not be the cause, but a compensatory effect to the hair loss.[13] As loss of melanin synthesis in telogen hair follicles may result in increased Vitamin D synthesis in the skin.[35]

Additionally, results of the current study revealed that mean serum 25(OH) Vitamin D levels in TE patient group after 3 months therapy with oral Vitamin D was significantly increased after therapy, P < 0.001 without a statistically significant difference between acute and chronic TE groups, P = 0.711.

Up to now best knowledge, there are no studies evaluating the oral supplementation of Vitamin D in patients with TE.

Regarding the effect of 3 months treatment with oral Vitamin D on the hair shedding score of TE patients included in this study, the mean score was significantly improved after treatment, P = 0.001.

Sattar et al. 2021[36] observed that the use of oral Vitamin D3 200,000 IU fortnightly for 3 months (in total six treatments per woman mostly belongs to low or middle socioeconomic level with a mean age of 32 + 1.5 years in South Punjab, Pakistan, resulted in significant improvement in hair regrowth in the patients of TE.

It was suggested that screening for serum 25(OH) Vitamin D levels might be beneficial in the management of TE; however, data on the effects of Vitamin D supplementation in hair loss is lacking.[35]

Vegesna et al.[37] demonstrated that in nude mice, the application of Vitamin D led to a dramatic stimulation of hair growth, associated with increased expression of several hair keratins.

Limited studies have been done in humans to elaborate the role of Vitamin D in the hair cycle. A potential application for Vitamin D is in chemotherapy-induced alopecia. Topical calcitriol has been shown to protect against chemotherapy-induced alopecia caused by paclitaxel and cyclophosphamide.[38] Of note, the studies in which no effects were observed, were small and may have used doses of Vitamin D that were inadequate to protect against chemotherapy-induced alopecia.[39]

For the patient satisfaction, 25% were slightly satisfied, 25% were moderately satisfied, and 50% were highly satisfied.

As regard correlation between serum 25(OH) Vitamin D levels and other data, nonsignificant correlation between Vitamin D and age, and duration of disease was found. On the other hand, a significant positive correlation was found between serum 25(OH) Vitamin D levels and family history of disease and significant negative correlation was found between serum 25(OH) Vitamin D levels and stress.

In our study, the selected cutoff values for diagnosing telogen patients from controls was 23 mg/dl with 92.5% sensitivity, 100% specificity, 100% PPV, 87% NPV, and 95% accuracy. The AUROC was 0.994, This means that TE could be predicted in hair loss cases if serum Vitamin D is <23 mg/dl.

To our knowledge, no prior studies included ROC curve for Vitamin D in TE to compare with.

From all the above, oral Vitamin D has a promising effect in TE treatment but results need to be verified on larger sample size and there is a need for evidence-based data for the recommendation of Vitamin D supplementation, the exact dose, duration and follow up in hair loss patients especially TE cases.

CONCLUSION

• Lower levels of Vitamin D3 may be linked to TE pathogenesis

• Moreover, oral Vitamin D has a promising effect in TE treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.