The following is a recording from the live webinar held Dec 13 2023. It is an annual webinar that celebrates that top 20 hair research studies of the prior year.
A new study showed that patients with CCCA have a higher prevalence of autoimmune, atopic, metabolic, and psychiatric comorbidities. Prior studies have examined some of the cormorbidites that might exist with CCCA. Some of these studies suggested that CCCA is associated with several comorbidities including diabetes, metabolic dysfunction, bacterial scalp infections and uterine leiomyomas.
Authors of a new study set out to investigate comorbidities that are associated with CCCA. The database used was the National Institute of Health’s All of Us research program database.
There were 201 patients with CCCA. Each patient with CCCA was matched to one age-, race-, ethnicity-, and gender-matched control. CCCA patients, compared to controls, were more likely to have metabolic abnormalities: hyperlipidemia (OR: 5.20, 95% CI: 3.37–8.03), hypertension (OR: 8.62, 95% CI: 5.46–13.59), and type 2 diabetes (OR: 5.66, 95% CI: 3.46–9.25).
CCCA patients were also found to have increased odds of having an autoimmune condition (OR: 4.92, 95% CI: 2.58–9.34).
CCCA patients were more likely to have atopic disease including allergic rhinitis (OR: 6.03, 95% CI: 3.54–10.26), asthma (OR: 3.55, 95% CI: 2.08–6.05), and atopic dermatitis (OR: 4.94, 95% CI: 1.40–17.47).
Regarding psychiatric conditions, there was also an increased prevalence of anxiety (OR: 5.37, 95% CI: 3.39-8.52), and depression (OR: 3.23 95% CI: 2.10-4.98), in CCCA patients, suggesting that CCCA may bear a negative quality of life impact.
Overall, the authors showed that CCCA patients have higher odds of autoimmune, atopic, metabolic, and psychiatric comorbidities. The authors data match other studies showing the significancy increased risk of metabolic dysfunction.
The increased autoimmune conditions may suggest that abnormal T-cell licensing underlies the pathophysiology of CCCA. The increased allergies in CCCA may indicate the role of the T-helper-2 (Th2) cell axis in mediating CCCA.
Some studies suggested CCCA is associated with breast cancer and uterine leiomyomas. These were not studied here but would be valuable to note if this database could evaluate these risks.
Joshi TP et al. Comorbidities in patients with central centrifugal cicatricial alopecia: a case-control study. . Int J Dermatol. 2023 Nov 23.
Workplace bullying is a persistent pattern of mistreatment from others in the workplace that causes either physical or emotional harm.
Authors of a new study set out to better understand the frequency of workplace bullying among patients with alopecia areata and how bullying was addressed.
Authors used a questionnaire known as the Negative Acts Questionnaire-Revised Scale to assess bullying. This is a 22- item validated tool assesses workplace bullying within the last 6 months using a 5-point Likert scale corresponding to frequency of events. Scores range from 22 to 110 and correspond to being never bullied (<40), occasionally bullied (40–56), and severely bullied (>56)
The questionnaire was administered to the National Alopecia Areata Foundation database to evaluate workplace bullying in patients with AA.
There were 673 patients who ultimately met the inclusion criteria completed the survey. Most respondents were female (n = 537, 79.8%) and Caucasian (n = 508, 75.5%) with an average age of 46.8 years. Most patients were employed full-time (n = 427, 63.4%)
21.67% (n = 146) of individuals with AA experience workplace bullying with an average NAQ-R score of 56.1. This corresponds to the cut off for being considered ‘severely bullied’
53.8% of patients with AA reported frequently having their “opinion ignored” and 47.7% reported “being ignored or excluded” and 44 % reported the “spreading of gossips and rumors” by others.
There were several barriers to reporting bullying
43.5 % identified the “stress associated with filing a complaint”
36 % of patients worried that reporting the bullying might have a negative effect on future career aspirations.
Among individuals who self-reported bullying (n = 160), 75.0% (n = 120) chose to address the behavior.
The most common action when bullied is to discuss it with a manager. Some also discussed with family and friends. 25 % of patient did not take any action. Other options include those shown here:
The most common consequences of addressing the bullying behavior were “the behavior continued” (30.8%, n = 37) 28.3 % of patients left their job. Other responses are shown below.
Workplace bullying is an important problem for patients with alopecia areata. About 1 in 5 patients report bullying. It’s not easy to report bullying. Patients report that there are stresses associated with filing a complaint and there are potential effects on future career options. Some bullying was noted to continue even after some individuals addressed the behavior.
There is an important and urgent need to develop strategies to reduce bullying. This may start with helping patients recognize all the aspects of workplace bullying and helping them to understand their options when this occurs. Strategies may also include continued education of the public and workplace.
REFERENCE
Li SJ et al. Experiencing Workplace Bullying in Patients with Alopecia Areata: A Cross-Sectional Survey Study. Skin Appendage Disord. 2023 Aug;9(4):258-261.
Recently published reports from some parts of the world have reported the onset of AA in some individuals who received the COVID-19 vaccination. We’ve been covering this topic for a while now.
A study by Chen and colleagues examined the question “do vaccines increase the risk of developing alopecia areata?”
The authors performed a retrospective cohort study of patients with AA diagnosed at Arrowhead Regional Medical Center (ARMC) in Colton, CA at the demographic levels of age group, sex, and race. All cases of initial diagnosis of AA at ARMC occurred between December 17, 2020, and February 10, 2023. The study period was chosen to include the period from the initial COVID-19 vaccination administration to the time of data acquisition for this study.
Between December 17, 2020, and February 10, 2023, 1,402,255 residents had been either fully or partially vaccinated for COVID-19, while 785,250 had not received a vaccination at all. Over the same period, 73 patients at the medical center received an initial diagnosis of AA. Of those 73 patients, 36 had not received a COVID-19 vaccination before the diagnosis of AA, while 37 had been either partially or fully vaccinated for COVID-19. The incidence of AA calculated with the provided 73 AA patients in a 1,402,255 population is roughly 0.0052%
The probability of acquiring AA was lower in the vaccinated group overall, with an OR of 0.58 (95% CI = 0.35 to 0.94) and a p-value of 0.02. The risk of AA was also lower among the vaccinated females, with an OR of 0.32 (95% CI = 0.16 to 0.62) and a p-value of <0.05.
SOURCE: Chen J et al. The Incidence of Alopecia Areata in a COVID-19- Vaccinated Population: A Single-Center Review. Cureus 2023. Used with creative commons license.
This is an interesting study. It points to the possibility that vaccines don’t increase the overall risk of developing AA – at least in this part of the United states. These types of studies are challenging to conduct and interpret and the authors don’t exclude the possibility there are confounding factors here or limitations to the conclusion. Nevertheless, the study provides helpful information that by evaluating over 2 million patients living in a certain area – the risk of new onset AA did not seem increased.
The study does not evaluated whether vaccines flare existing AA or whether there are groups where the vaccine decrease AA and groups where it might increase AA.
Reference
Chen J et al. The Incidence of Alopecia Areata in a COVID-19- Vaccinated Population: A Single-Center Review. Cureus 2023
Acne keloidalis is a chronic scarring alopecia characterized by the development of papules, nodules, plaques and/or tumorous masses – typically starting in the lower occipital area of the scalp. The cause is not clear although trauma to the scalp is thought to play a role including close shaving, friction, heat and humidity.
Authors of a new study set out to perform a retrospective and multicentre international review of 79 patients with a confirmed diagnosis of AKN. Patients were from Spain, Australia and Italy.
The study included 79 patients (75 men and 4 women) with a median age at diagnosis of 35 years were included. 42% were Caucasian, 8% middle eastern, 20 % African, 12 % African American, 14% south American and 5 % Asian.
In terms of predisposing factors, 38% had straight hair, 25% have wavy hair and 38% had curly hair. In terms of prior triggers, prior use of a razor to the back of the scalp was noted in 41% of patients. 17% previously used a helmet.
18% were obese, 6% had high blood pressure, 13 % had high cholesterol, 5% had diabetes, 9% had acanthosis nigricans. 12% had keloids in other areas of the body (with median number being 3). 20 % had pseudofolliculitis barbae, 12 % hidradenitis, 14% acne conglobate, 1 % pilonidal sinus, 6% dissecting cellulitis, 20 % folliculitis decalvans.
Severity
In terms of severity, 59% of patients had discrete papules and nodules, 18 % had merged papules and nodules, 12 % had plaques and 12 % tumerous mass. In terms of severity according to height of involvement in the occipital region (Umar classification). 41 % were less than 3 cm, 33 % were 3-6.5 cm, 26 % were more than 6.5 cm and none were widespread .
Straight hair was associated with less than 3 cm distribution of the lesions and wavy hair was associated with 3–6.5 cm distribution.
The authors described an incredibly large array of treatments that were used in attempt to treat the AKN. Intralesional steroids was the most performed treatment modality followed by oral retinoids and oral and topical antibiotics.
19% of patients had no improvement with treatment but a high proportion of patients did have improvement. 26% had mild improvement, 18% had moderate improvement and 37% had significant or complete improvement.
Patients with a less than 3 cm distribution of the lesions or with discrete papules and nodules had a greater probability of important or complete improvement after treatment in comparison to the more than 6 cm distribution of the lesions group and the patients with merged papules and nodules.
I liked this study as it draws attention to an scarring alopecia that is still very much a challenge to treat. Its exact pathogenesis is also not clear.
There are limitations to this study. These include lack of a control group and also the lack of matching the grade of improvement with the therapeutic modality.
But what I liked about this study is its focus on the complex disease associations that exist in AKN. It’s clear that features of the metabolic syndrome are very prevalent in AKN. In this study, a high proportion have overweight/obesity (66.7%) and dyslipidemia (13%), hypertension (6%) and diabetes (5%)
This study supports that general notion that metabolic syndrome is increased in AKN and this is therefore an important call to action for the patient.
A large study by Kridin et al in 2020 of 2677 patients with AKN and 13,190 controls also drew attention to the issue of metabolic syndrome. The prevalence of the MS was 3 times greater in patients with AKN than in control subjects (16.1% vs. 6.6). Obesity demonstrated the strongest association with AKN (OR 3.00; 95% CI 2.75-3.28), followed by type 2 diabetes mellitus (OR 2.47; 95% CI 2.20-2.77), hypertension (OR 1.82; 95% CI 1.63-2.05), and dyslipidemia (OR 1.60; 95% CI 1.46-1.75).
A 2017 study by East Innis et al found that the presence of any component disease of the metabolic syndrome (OR = 14, P = 0.008) and specifically hypertension (OR = 6.75, P = 0.036) were significantly associated with the extension of the lesions beyond the nape and occipital scalp.
Other follicular and scarring alopecias as common too. It’s well known that PFB is common in AKN and this study confirmed that 1 in 5 patients with AKN had PFB. But other scarring alopecias are common including folliculitis decalvans (20% and dissecting cellulitis (6%). So we should not be confused if we are diagnosing 2 conditions in our patients.
Components of the follicular occlusion tetrad (hidradenitis, acne conglobata, dissecting cellulitis, pilonidal cysts) are found in a significant proportion of AKN patients. Patients may not always tell us about these as they feel they are not related – so we must ask. These issues can be debilitating.
The study also reminds us that treatments are helpful for some patients with AKN. While It’s true that 1 in 5 patients had no improvement, nearly one third had complete improvement. This information is important as patients often ask me if it’s worth treating or not.
Lobato-Berezo A et al. Acne keloidalis nuchae: An international multicentric review of 79 patients. J Eur Acad Dermatol Venereol. 2023 Nov 1.
Kridin K et al. Acne Keloidalis Nuchae and the Metabolic Syndrome: A Population-Based Study. Am J Clin Dermatol. 2020 Oct;21(5):733-739.
East-Innis ADC et al. Acne keloidalis nuchae: risk factors and associated disorders - a retrospective study. Int J Dermatol. 2017 Aug;56(8):828-832.
I enjoyed the opportunity to join Dr James Del Rosso, esteemed US dermatologist and host of the wonderful “Derms and Conditions” podcast for 2 podcast episodes dedicated to … hair loss!
In part 1, we discuss alopecia areata, JAK inhibitors, trichoscopy and more.
Thanks to Dr Del Rosso and the Derms and Conditions podcast group for this kind invitation.
Listen on any of your favorite podcast platforms.
CLICK HERE TO LISTEN TO THE EPISODE
In keeping with the annual year-end tradition, Dr Donovan announces choices for the top 20 hair research studies of the past year. This year’s public webinar will take place Dec 13 at 5 pm PST (8 pm EST). The 20 studies will be discussed at the webinar.
Registration is required for the webinar and this can be done using the links below:
REGISTER FOR THE TOP 20 HAIR RESEARCH STUDIES of 2023
A recording of the webinar will be made available at a later date on the DonovanMedical youtube channel and broadcast to the Evidence Based Hair Podcast as well.
DERMATOPATHOLOGY
Douglas A et al. Scalp Biopsy Influences Diagnostic Accuracy and Treatment in Black Women with Alopecia: A Retrospective Study. J Am Acad Dermatol. 2023 Jan 31;S0190-9622(23)00157-3.
ANDROGENETIC ALOPECIA
Gupta AK et al. The relative efficacy of monotherapy with 5-alpha reductase inhibitors and minoxidil for female pattern hair loss: A network meta-analysis study. J Cosmet Dermatol. 2023 Jun 29
Jimenez-Cauhe J et al. Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients. Actas Dermosifiliogr. 2023 Aug 29:S0001-7310(23)00679-8.
ALOPECIA AREATA
Gandhi et al. The Association of Alopecia Areata-Related Emotional Symptoms with Work Productivity and Daily Activity Among Patients with Alopecia Areata. Dermatol Ther (Heidelb). 2023 Jan;13(1):285-298.
Li SJ et al. Experiencing Workplace Bullying in Patients with Alopecia Areata: A Cross-Sectional Survey Study. Skin Appendage Disord. 2023 Aug;9(4):258-261
Kazmi A et al. Switching between tofacitinib and baricitinib in alopecia areata: A review of clinical response. J Am Acad Dermatol. 2023 Apr 4;S0190-9622(23)00532-7.
King B et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. Lancet. 2023 May 6;401(10387):1518-1529.
George P et al. Incidence Rates of Infections, Malignancies, Thromboembolism, and Cardiovascular Events in an Alopecia Areata Cohort from a US Claims Database., Dermatol Ther (Heidelb). 2023 Aug; 13(8): 1733–1746.
Wang C-W et al. Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations. Clin Immunol. 2023 Oct:255:109737.
Chen J et al. The Incidence of Alopecia Areata in a COVID-19- Vaccinated Population: A Single-Center Review. Cureus 2023
TELOGEN EFFLUVIUM
Michelini S et al. Telogen Effluvium in SARS-CoV-2 Infection: histological aspects. J Eur Acad Dermatol Venereol. 2023 Mar 8.
TINEA CAPITIS
Gold, JA et al. Inadequate diagnostic testing and systemic antifungal prescribing for tinea capitis in an observational cohort study of 3.9 million children, United States. J Am Acad Dermatol. 2023 Feb 15;S0190-9622(23)00189-5.
COSMETIC DERMATOLOGY
Landau M et al. Nonscarring alopecia after temporal lifting technique with dermal fillers. JAAD Case Rep. 2023 May 12;37:30-34
GENERAL SCARRING ALOPECIA
Kim SR et al. Association of Primary Cicatricial Alopecia with Subsequent Cardiovascular Disease. J Invest Dermatol. 2023 Nov 19:S
LICHEN PLANOPILARIS
Lim SH et al. Prevalence and Incidence of Comorbid Diseases and Mortality Risk Associated with Lichen Planopilaris: A Korean Nationwide Population-Based Study. Clin Exp Dermatol. 2023 Jul 11;llad235
FOLLICULITIS DECALVANS
Matard B et al. Folliculitis decalvans and dystrophic epidermolysis bullosa: a significant association. Br J Dermatol 2022 Dec;187(6):1026-1028.
DISCOID LUPUS
Fredeau L et al. Risk factors of progression from discoid lupus to severe systemic lupus erythematosus: a registry-based cohort study of 164 patients. J Am Acad Dermatol. 2023 Mar;88(3):551-559.
DISSECTING CELLULITIS
Cajas-Garcia MS et al. Distinct presentations of scalp dissecting cellulitis manifesting with furrows and gyri. J Eur Acad Dermatol Venereol. 2023 Feb 3.
CENTRAL CENTRIFUGAL CICATRICIAL ALOPECIA
Joshi TP et al. Comorbidities in patients with central centrifugal cicatricial alopecia: a case-control study. Int J Dermatol. 2023 Nov 23.
ACNE KELOIDALIS NUCHAE
Lobato-Berezo A et al. Acne keloidalis nuchae: An international multicentric review of 79 patients. J Eur Acad Dermatol Venereol. 2023 Nov 1.
The measurement of the length of the second and fourth fingers has been argued by some to provide a crude measurement of exposure to androgens in utero and an estimate of risk of androgen related disorders. Some have proposed that a lower 2D:4D ratio may signify elevated levels of perinatal testosterone, thereby providing a surrogate marker of an increased risk to develop androgenetic alopecia. The 2D:4D ratio has been utilized to predict the risk of hyperandrogenism, increased body mass index and waist-to-hip ratio, and benign prostatic hyperplasia.
To measure the 2D:4D ratio, the lengths of second digit (index finger) and fourth digit (ring fingers) are measured from the fingertip to the midpoint of the basal crease, on the ventral surface of the hand. They are best measured using digital vernier calipers for greater accuracy. More commonly a ruler is done when sophisticated calipers are lacking. The 2D:4D ratio is obtained by dividing these values. Usually, two or more measurements are taken to ensure the greatest reliability. The mean of the multiple measurements are taken for right and/or left hand and divided for the calculation of 2D:4D ratio of the right and left hands separately. Some have argued that the right digit ratio is more differentiated and sensitive to prenatal testosterone exposure. Many researchers report an “averaged” 2D:4D ratio across both hands
A nice review by Almashali M et al. summarizes what we know about the 2D to 4D ratio in AGA. The authors show us that 4 studies have been published that address this issue. Three studies suggest a role for the 2D:4D ratio to predict AGA and one large study suggests there’s really not much evidence at all (except maybe in individuals over 40 years of age).
A study by Chen et al from 2022 showed that individuals with a right-hand 2D:4D less than 0.947 may have a more severe form of AGA (P = 0.036). The authors found that the marker really becomes even more reliable as one ages. In other words, older individuals with a low 2D:4D were more likely to have androgenetic alopecia.
The largest study on the subject was a 2016 study from Iran by Feily A and colleagues. The authors studied 1200 males with AGA and found no link between AGA and 2D:4D ratio. However, the authors did find that when data was stratified according to age, there was a positive correlation between a low 2D:4D and the risk of AGA in those older than 40 years of age. Taken together, the authors proposed that the the 2D:4D may not be used to determine a patient’s likelihood of developing AGA without also considering the patient’s age. it’s much more useful of a test in older adult males.
Table from
Almashali M et al. The Use of 2D:4D Digit Ratio as a Predictor of Androgenetic Alopecia: A Review. Dermatol Pract Concept. 2023 Oct 1;13(4):e2023237.
Chen WC, Hsu WL, Chen JY, Shih NH, Wu CY. Second-to-fourth digit ratio and age predicting the severity of androgenetic alopecia: a cross-sectional study. Aging Male. 2022;25(1):242–248.
Feily A, Hosseinpoor M, Bakhti A, et al. Digit-Length Ratios (2D:4D) as a Phenotypic Indicator of in Utero Androgen Exposure is Not Prognostic for Androgenic Alopecia: a Descriptive-Analytic Study of 1200 Iranian Men. Dermatol Reports. 2016;8(1):6386.
Unal M. Digit ratio 2D:4D is a possible indicator for androgenetic alopecia in males. J Cosmet Dermatol. 2018;17(3):545–548.
Bilgic Ö, Altınyazar HC, Eryılmaz D, Tuğrul ZA. Are 2D:4D finger-length ratios an indicator of androgenetic alopecia in males? An Bras Dermatol. 2016;91(2):156–159.
Authors of a new study set out to evaluate whether patients with AGA are at risk for macular degeneration and whether simple blood tests for microinflammation could asses the risk.
To do so, the authors performed a case control study with 40 patients with AGA aged 40 years or more of both sexes and 40 control subjects. Patients underwent examinations of the skin and eyes. Blood tests were performed for a variety of tests including the monocyte to HDL ratio (MHR) which authors felt was a good marker of ‘microinflammation.’
The authors found that the mean MHR was significantly higher in AGA patients (6.98 ± 2.21) than in controls (3.82 ± 0.68) (P < 0.001). Surprisingly the authors found that 80 % of AGA patients were diagnosed with age related macular degeneration compared to just 20% of control subjects. Male patients with more severe AGA were more likely to have macular degeneration. Interestingly, the mHR was significantly higher in AGA patients found to have AMD (9.37 ± 1.1 and 7.01 ± 1.42 in the wet and dry type respectively) compared to patients without AMD (P < 0.001).
This is an unexpected report. The authors suggest that macular degeneration may develop more frequently in those with androgenetic alopecia. Moreoever the authors propose that the MHR might serve as a potential biomarker for predicting AMD in AGA patients.
For those not aware, I’d like to spend a moment talking about monocytes and HDL and how these all factor in when it comes to inflammation. Inflammatory cells known as monocytes are known to be major source of “proinflammatory” species during atherogenesis. In atherosclerosis, modified low-density lipoproteins (LDLs) are removed by macrophages; these are recruited in the vessel wall, inducing the release of inflammatory cytokines in inflamed tissue. Hence, inflammatory cholesterol ester-loaded plaque is generated.
High-density lipoprotein-cholesterol (HDL-C) exhibits “anti-atherosclerotic” effects by neutralizing the pro-inflammatory and pro-oxidant effects of monocytes. HDL does this by inhibiting the migration of macrophages and LDL oxidation in addition to the efflux of cholesterol from these cells. Furthermore, HDL plays a role in blocking the activation of monocytes and proliferation-differentiation of monocyte progenitor cells.
Taken together it has been proposed that the accumulation of monocytes and reduction of HDL-C may participate in atherosclerosis and cardiovascular disease.
MHR has been found to increase with age and with a variety of inflammatory diseases including fatty liver, insulin resistance, post stroke depression, resistance blood pressure problems, sleep apnea, pulmonary hypertension. In psoriasis, MHR is closely linked to the PASI (severity) score. These are only a short list of inflammatory conditions linked to MHR
Shams GM et al. Age-Related Macular Degeneration in Patients with Androgenetic Alopecia: Could the Monocyte/HDL Ratio Be the Link? Dermatol Pract Concept. 2023 Oct 1;13(4). doi: 10.5826/dpc.1304a285.
Ganjali S et alMonocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol . 2018 Dec;233(12):9237-9246.
Authors of a new study set out to re-examine the complete data from the BRAVE AA1 and BRAVE AA2 baricitinib trials to see if eyebrow and eyelash regrowth could still occur to significant levels even if scalp hair regrowth was not occurring. The authors examined eyebrow and eyelash regrowth patterns in patients with AA who had a poor response to scalp regrowth (SALT ≤ 20 response), intermediate response to scalp regrowth (achieved a 30% improvement from baseline (SALT30) without a SALT score ≤ 20), or non-responders (never achieved SALT30).
After 52 weeks of treatment with baricitinib 4 mg treatment, 70 % of scalp responders have complete or near complete regrowth of eyebrows and eyelashes. In contrast, complete or nearly complete regrowth of eyelashes and eyebrows occurred in 50% of patients with intermediate response and 20% of non-responders.
All in all, the authors found that clinically meaningful regrowth in eyebrow and eyelash hair can occur with baricitinib treatment even if scalp hair regrowth does not occur .
Senna MM et al. Clinical Benefits of Baricitinib Therapy According to Scalp Hair Regrowth in Patients with Severe Alopecia Areata. Dermatol Ther (Heidelb). 2023 Nov 22. doi: 10.1007/s13555-023-01063-2. Online ahead of print.
The side effects of minoxidil do not typically include anything to do with the lungs. Typical side effects of topical minoxidil include shedding, irritation, palpitations, hypertrichosis. Rare side effects include chest pain, facial swelling, parasethesias. Oral minoxidil side effects include fluid retention in the feet and rarely the body as well as hypertrichosis, dizziness, palpitations and headaches.
Earlier this year, we reviewed an interesting study of hypersensitivity pneumonitis from oral minoxidil. I have included a link to that study here:
Authors of a new study report a patient with drug induced lung disease from topical minoxidil. The patient’s lung function and chest x ray was observed to worsen with minoxidil use and then improved when minoxidil was stopped. Thoracoscopic lung biopsy samples showed interstitial pneumonia and granulomas.
This is an interesting report which reminds us of the need for open mindedness when considering side effects of our hair loss drugs. Minoxidil is a generally safe medication with infrequent side effects. However, side effects can occur.
Ishiguro T et al. Drug-induced lung disease due to topical minoxidil. Respir Med Case Rep. 2023; 46: 101940.
Prior studies have suggested that oral minoxidil is not always better than topical. For example, in 2020, Dr Ramos and colleagues showed that 1 mg oral minoxidil was similar in effectiveness to 5 % minoxidil in women.
A new study from Iran shows similar findings to the Ramos study. Authors in this study randomized 65 patients (male and female) to either 1 mg oral minoxidil or 5% topical minoxidil (1 cc twice daily for men and 1cc once daily for women) for 6 months and looked at outcomes 6 months later. Hair improvements were similar in the two group and one group was not superior to the other. There were more patients in the oral minoxidil group who had low blood pressure and excessive hair growth but overall treatments were well tolerated in both groups.
All in all, this study lends support the concept that 5 % minoxidil and 1 mg oral minoxidil are likely to be similarly effective for treating androgenetic alopecia. The study is small and complicated by including both male and female patients and by including topical minoxidil and different doses (twice daily in men and once daily in women). Nevertheless, it lends support to the notion that topical minoxidil is not likely to be inferior to 1 mg oral minoxidil.
REFERENCE
Asilian A et al. Clinical efficacy and safety of low-dose oral minoxidil versus topical solution in the improvement of androgenetic alopecia: A randomized controlled trial. J Cosmet Dermatol. 2023 Nov 29.
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Deuruxolitinib is a Janus kinase (JAK) 1 and JAK2 inhibitor. It has been studied in the THRIVE-AA1 and THRIVE-AA2 clinical trials. In these studies, adult patients with AA were randomized to 8 mg BID and 12 mg BID doses vs placebo. At 24 weeks, about 30 % of patients using deuruxolitinib 8 mg twice daily achieved good regrowth. In other words, they met the typical AA study endpoint that denotes good regrowth (ie SALT score less than 20).
Concerns were raised in 2023 with deuruxolitinib at the 12 mg twice daily dose. Blood clots in patients receiving these doses caused the FDA to pause clinical trials of deuruxolitinib. We’ve discussed these issues in the past and a link to prior articles is here:
New data that was presented at a recent meeting of the European Academy of Dermatology and Venereology showed that an even greater number of patients achieve the SALT 20 endpoint by week 52 compared to week 24. Dr King presented week 52 data as part of the company’s open label study. Here, patients received either 8 mg BID or 12 mg BID oral deuruxolitinib. After 52 weeks of cumulative dosing, 63.6% of patients in the 8 mg BID group achieved a SALT score less than 20. This was similar (62.1%) in the 12 mg BID group.
This is exciting data. It would appear that deuruxolitinib is effective in treating advanced AA. It’s a bit surprising that the 12 mg BID dosing and 8 mg BID dosing produce similar clinical outcomes. That’s not a dose response we typically see with our other JAK inhibitors. In other words, for most other JAK inhibitors, higher doses of the drug bring better results.
The time draws near that various regulatory bodies around the world will need to consider approving deuruxolitinib. I’d be surprised if any dose other than the 8 mg dose goes up for consideration. Personally, what’s left for me as a hair specialist is:
1) to closely follow over time if the safety of deuruxolitinib is the same as other JAKs,
2) to follow if deuruxolotinib is truly more effective than other JAKs or just as effective at 8 mg BID dosing over 2, 3 and 5 years of observation
and
3) what will be the final cost of this drug.
The graph below shows the proportion of patients using baricitinib and ritlecitinib that achieve reasonably good regrowth (SALT <20) and includes data up to 1 year. It shows the proportion of patient who achieve 80 % regrowth (ie SALT less than 20). If 60 % of those treated with 8 mg BID deuroxolitinib achieve a SALT less than 20 that would put deuruxolitinib as a top performing JAK inhibitor - at least at week 52. I hope to review all the data at some point - everything on the table. Long term studies of safety as well as effectiveness are key for all JAK inhibitors but especially JAKs that have already been issued warnings in their trials. Similar to all JAK inhibitors, we’ll need to follow deuruxolitinib long term data on blood clots, cancer, heart disease and infections.
REFERENCE
ABSTRACT 6743 - https://eadv.org/wp-content/uploads/scientific-abstracts/EADV-congress-2023/Hair-and-nail-disorders.pdf
As a hair doctor, I test the health of my patients’ livers quite often. AST and ALT are the typical blood tests that I order. Most often, I’m testing it before we start certain types of oral medications that could affect the liver. Methotrexate, JAK inhibitors, hydroxychlorqouine, mycophenolate are good examples of drugs that have the potential to affect the liver and therefore need baseline blood tests before starting.
Sometimes, liver enzyme levels come back elevated before we start a new drug and the question arises - what’s causing this?
A variety of possibilities exist including metabolic syndrome, alcohol use, medications the patient uses, autoimmune liver disease, fatty liver disease, hepatitis, obesity, cancer and more. This list is potentially quite long.
It has been estimated that there are about 80,000 herbal and dietary supplements on the market. It is increasingly appreciated that some are associated with a chance of liver injury.
A new study reminds us that liver injury from turmeric could be increasing in the United States. authors identified 10 cases of turmeric-associated liver injury in a database of liver injury patients between 2011 and 2017. 8 patients were women and 8 were white. Median age was 56 years. Liver disease started 1-4 months after starting the drug. 5 were hospitalized and 1 died. HLA typing demonstrated that 7 patients carried HLA-B*35:01 indicating that there could be a genetic prediposition to liver injury.
REFERENCE
Halegoua-DeMarzio D et al. Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN] Am J Med. 2023 Feb;136(2):200-206
Navarro VJ et al. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363. Epub 2016 Nov 17.
I’ve selected a new submission for this week’s question of the week.
SPIRONOLACTONE VS FINASTERIDE: WHICH IS MORE LIKELY TO CAUSE WEIGHT GAIN? CONCERNS ABOUT LOW ALP?
To submit a question for consideration, visit our Question of the Week
Telogen effluvium occurs via a number of mechanisms but often occurs 2-3 months after a trigger. Common triggers of telogen effluvium include stess, low iron levels, thyroid problems, medications, weight loss and infection.
Studies have shown that COVID shedding can sometimes occur sooner than the typical 2-3 months. A new study from Thailand interviewed 43 patients with hair loss after COVID. Shedding occurred on average around 1 month after infection. Females had more severe shedding than males.
For other articles related to COVID related shedding, click on the link:
REFERENCE
Triwongwaranat D et al. Characteristics of hair loss in COVID-19 patients in Thailand. Medicine (Baltimore). 2023 Dec 8;102(49):e36539. doi: 10.1097/MD.0000000000036539.
I’ll be speaking at the Scarring Alopecia Foundation “Scarring Alopecia Summit” on Saturday. This is a free conference for patients with scarring alopecia. I’ve been asked to speak about several scarring alopecias including the ones shown here.
Follow the link here to sign up or to contact SAF for more information.
https://scarringalopecia.org/scarringalopeciasummit2023/
Pfizer announced today the Health Canada approval of ritlecitinib (LITFULO) for treatment of severe alopecia areata in patients 12 and over. The drug belongs to the group of JAK inhibitors which are well known to be effective in treatment alopecia areata. Ritlecitinib is now the first formally approved JAK inhibitor in Canada although other JAK inhibitors have been used off label for many years in treating alopecia in Canada and continue to be used off label including tofacitinib, baricitinib, upadacitinib and others.
The formal approval is important as it marks a commitment from the company and Health Canada to formally study the long term effects of this medication. It is also important as it may lead to the drug being approved by insurance companies in Canada. The hope is that this drug will prove safe and effective in the long term as patients with severe alopecia areata will generally need to take this drug forever. Patients with more mild forms of AA (50-75% loss) might be able to eventually reduce the dose if they have been stable for a long time.
This drug does not help everyone with alopecia but helps a significant proportion. After about 1 year of use, the drug helps about 30 % of patients with severe alopecia areata achieve outstanding results (known as SALT SCORE less than 10) and about about 45% achieve pretty good results (SALT SCORE less than 20). Patients with severe alopecia areata respond slightly less well compared to patients with less severe AA.
Long term side effects are unknown but continue to be studied.
I have discussed this drug in a public webinar several months ago. A recording is found here. All in all, this is an important milestone for Canadians with alopecia areata.
6 years ago, I sat down at my desk at the end of a busy clinic and scribbled on a piece of paper an outline to what would eventually become an outline to the future Evidence Based Hair Fellowship (EBHF) training program. At that time, I had just finished hosting a visiting dermatologist in my clinic for the week. We spent the week together reviewing patients together and discussing some really tough cases. The visiting dermatologist was bright and enthusiastic and as we often say as an expression - the dermatologist was a “sponge” for new information.
At the very end of the week, we said our final goodbyes and my dermatology guest left my office. I returned to my desk, sat down and picked up a pen and started writing.
It was clear to me that evening that what this dermatologist really needed now was not another visit to another clinic. What this dermatologist needed now was a challenging and stimulating training program that could help him even further develop the kinds of skills that will be needed for a lifelong practice in hair loss medicine. It was clear to me that what this dermatologist needed now was the opportunity to read more about hair loss and be guided to do so, the opportunity to be challenged, an opportunity to fully commit to answering questions and solving diverse problems about hair loss in children and adults.
That evening was the source of many of the ideas that would serve as foundations for the Evidence Based Hair Fellowship Training Program.
That was 2017.
Thinking carefully about the needs of trainees was something I thought alot about even before 2017. Training doctors about hair loss was something that I did often. I had many training opportunities for doctors in my clinic. In fact, I hosted dermatologists for an intensive week long training program in Toronto, Canada for several years. The “International Hair Course” was great intense and fun and we learned alot of new information and new skills in just a short week!
But the new training program I had in mind would be different. It would require an entirely new foundation. And so in 2017, I set out to lay the foundation that I felt was needed.
My first goal was to help a wider audience of learners realize the joys that come with studying hair loss. I hired a videographer and video editor and invited him to come with me to my lectures. We recorded the lectures and put these up on our website and youtube. My goal was to help learners appreciate the thinking process and problem solving that comes with treating patients with hair loss. At that time, there were few such educational videos and I wanted to fill a void. My hope was that learners from around the world could have access to knowledge.
My second goal was to help learners appreciate the value of hair loss research and how it shapes clinical practice. I also wanted learners to understand that not all hair loss research is good research and not all findings and conclusions published in medical journals are true, valid, applicable or justified. I knew this was a delicate matter but I knew this needed to be discussed. I wanted to develop a new venue for discussion of ideas and encourage others. In Dec 2020, I launched the “Top 20 Hair Research Studies of 2020” as a way to draw attention to good hair loss research - research that really changes what goes on the clinic. I also hoped that the discussion would stimulate further interest in a variety of areas of hair loss medicine.
Every December now, we celebrate the top 20 studies of the past year. It’s our tradition. This year, the Top 20 studies of 2023 is planned for December 13 2023. Join us!
My third goal was to help learners appreciate the incredible and fast paced evolution that was taking place in the field of hair loss medicine. There is a misperception that hair loss research does not occur and that nothing is happening in this field. This of course is not true - there is nothing stagnate about the field of hair loss medicine. The way we do things in 2018 is not necessarily the way we do things in 2022! My worry was that continued perpetuation of such a view would detract good people from getting involved in various aspects of the hair loss field. I launched the Evidence Based Hair podcast in 2022 as a means to capture some aspects of this exciting evolution of our field.
Finally on August 1 2023, I felt we were finally ready to announce the Evidence Based Hair Fellowship training program to the public. The program had goals to achieve what it came to achieve - to help practitioners develop new knowledge, new problem solving skills and new levels of skill in managing both straight forward and tough cases of hair loss. The program would welcome practitioners from across the world. It would provide a safe and stimulating environment for learners of all different levels. The ultimate judge of the EBHF program’s success would be the patients that are helped in the future by those who complete the rigorous EBHF program.
Dec 1, 2023 marks the final deadline for receipt of EBHF applications. It also marks the end of an important step for all of us here at the Donovan Hair Academy - finalizing the 2024-2025 EBHF training group. In the end, I’m so happy that we’ll be able to welcome approximately 100 EBHF fellows in Jan 2024 who will set out to learn about hair loss with an intensity and depth that will equip them extremely well to be our leaders of tomorrow.
It’s becoming clear that COVID VACCINES and COVID INFECTION can both potentially TRIGGER alopecia areata. Add to this one more finding - COVID VACCINES in some cases can PREVENT alopecia areata.
Wow, what complexity!
It's becoming increasingly clear that a variety of mechanisms need to enter the mind when seeing a patient with alopecia areata. Alopecia areata was a fairly common autoimmune condition before the pandemic so clearly patients are still developing alopecia areata for the same reasons they always developed alopecia areata.
We know that genetic factors and environmental factors play a key role in the development of alopecia areata. In fact, about 70 % of alopecia areata is explained by genetic factors and 30 % is probably due to the environment that the person lives in. Stress, infections, smoking, obesity and a wide variety of other factors are thought to be potential trigger alopecia areata.
But we now need to add COVID infection and COVID vaccines to the list of triggers. The list of contributing factors is growing pretty long and clearly all the factors aren't worked out.
There are a group of people out there in the world that are going to develop alopecia areata if they get COVID infection and there are a group of people out there in the world that are probably going to develop alopecia areata from getting COVID vaccines and there are a group of people out there in the world that are going to reduce their chance of developing alopecia areata by getting a COVID vaccine.
We don't yet know which is which and what recommendations to make! Recommending a vaccine to some will help reduce their chances of developing alopecia areata! Recommending a vaccine to others will increase their chances of developing alopecia areata!
Universal recommendations and universal templates rarely work well in the field of medicine as we have spoken about many times before. Clearly vaccines are needed. The decision on getting or not getting a vaccine is far more complex than the risk of developing alopecia areata and other factors need to be discussed on a case by case basis with one's doctor. Here, we are talking specifically about the risk of alopecia areata.
The story of hair loss is never quite as simple as one would think !
References
Wang C-W et al. Clinical characteristics and immune profiles of patients with immune-mediated alopecia associated with COVID-19 vaccinations. Clin Immunol. 2023 Oct:255:109737.
Pastukhova E et al. Alopecia Areata as a Sequela of COVID-19 Vaccination: A Systematic Review J Cutan Med Surg. 2023 Jan-Feb;27(1):64-65.
Genco L et al. Alopecia Areata after COVID-19 Vaccines. Skin Appendage Disord. 2023 Mar;9(2):141-143.
