The Possible Association of CCCA with Breast Cancer
Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that affects many black women age 35-60 years. A 2021 study from the University of Pennsylvania leads us in a potentially new direction in understanding comorbidities associated with CCCA.
The researchers performed a cross-sectional study of black women aged 18 years or older who presented to the University of Pennsylvania Health System over the 4 year period April 13, 2016, to April 13, 2020. Patients with CCCA were identified in electronic databases based on coding. Patients with breast cancer or colon cancer were also identified by standard coding.
There were over 225,000 black women treated during this four-year period within the University of PennsylvaniaHealth System. There were 742 patients identified with a clinical diagnosis of CCCA. 4.7 % of these women had a diagnosis of breast cancer compared to 1.8 % of controls. This corresponded to an odds ratio of 2.61. 149 of the 742 patients had a biopsy that confirmed the diagnosis of CCCA. 4.4 % of these 149 patients had a diagnosis of breast cancer, corresponding again to an evaluated odds ratio of 2.49.
There was no increased risk of colon cancer among women with CCCA.
Summary and Comment
This is an important study and opens the door for other confirmatory studies. These data suggest that women with CCCA may be at increased risk for breast cancer. I’m eagerly awaiting other studies that refute or confirm these findings.
Reference
Brown-Korsah JB et al. Association of breast and colorectal cancer in patients with central centrifugal cicatricial alopecia: A retrospective, cross-sectional pilot study. Journal of the American Academy of Dermatology 2021 Mar;84(3):859-860.
Eczema, Lupus, Urticaria and Psoriasis Top List of AA Comorbidities in Germany
Authors from Germany set out to evaluate the incidence, prevalence and comorbidities associated with alopecia areata. They used claims data from an insurance company and evaluated data between 2016 and 2020. The database included 2.9 million people
In 2020, AA prevalence was calculated to be 210 cases per 100,000 (0.2%) and incidence 72 cases per 100,000 (0.07%). Women were more likely to have AA than men (0.2 % vs. 0.1%). Compared with persons who did not have alopecia areata, patients with AA were more likely to have several disease comorbidities.
MEDICAL CONDITIONS MORE LIKELY IN AA (by FACTOR OF 2-3 FOLD RR)
atopic dermatitis
pruritus
lupus erythematosus
urticaria
psoriasis
ulcerative colitis
multiple sclerosis
nail disease
chronic fatigue syndrome
MEDICAL CONDITIONS MORE LIKELY IN AA (by FACTOR OF 1-2 FOLD RR)
rheumatoid arthritis,
thyroid disease,
allergic rhinitis,
chronic pancreatitis
osteoporosis
migraine
breast cancer
hypercholesterolemia
MEDICAL CONDITIONS LESS LIKELY IN AA
prostate cancer (RR 0.33, 95% CI 0.21−0.53)
MEDICAL CONDITIONS SHOWING NO DIFFERENCE IN AA
chronic kidney disease, chronic viral hepatitis B, chronic viral hepatitis C, colorectal cancer, fever of other and unknown cause, HIV, leukemia, lung cancer, lymphoma, metabolic disorder (unspecified), myocardial infarction, periodontitis, peripheral arterial occlusive disease of the extremities, renal insufficiency, schizophrenia, ulcer or uveitis.
Comment
This paper captures key epidemiologic information from patients with alopecia areata living in Germany.
The prevalence of AA was estimated at 0.2%, which is lower than the often-quoted statistic of 2%. However, this 2 % statistic seems high when you look at all the studies that have ever been published. It’s interesting that the data comes in at 0.2 %.
Many of the comorbidities identified in this study are consistent with those of other studies. Patients with AA are known to be at risk for atopic dermatitis, lupus, and psoriasis.
Are patients with AA at increased risk for breast cancer?
I was drawn to the data showing that patients in this study had an increased risk of breast cancer.
A 2018 study by Chen et al. also showed an increased risk of breast cancer (as well as lymphoma, kidney and bladder cancer). The Chen et al. study showed that women with alopecia areata under 50 had the highest risk of breast cancer. Not all studies have shown an association between breast cancer and alopecia areata. For example, the 2023 study by George et al. did not.
REFERENCE
Augustin M et al. Epidemiology of alopecia areata and population-wide comorbidities in Germany: analysis of longitudinal claims data. Br J Dermatol . 2024 Feb 16;190(3):374-381. doi: 10.1093/bjd/ljad381.
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.
Chen C-C et al. Cancer risk in patients with alopecia areata: a nationwide population‐based matched cohort study. Cancer Med. 2018 May; 7(5): 2153–2159. Published online 2018 Mar 25. doi: 10.1002/cam4.1448 PMCID: PMC5943418 PMID: 29577672
The “Bidirectional Relationship” Between Alopecia Areata and Thyroid Disease
We’ve discussed the concept of bidirectional relationships in prior articles of the Beyond the Scalp Blog. For review, be sure to check out the prior article, “Bidirectional Relationships in Hair Loss”
Common examples of these so-called “bidirectional relationships” include:
Alopecia Areata and the Risk of Depression
Alopecia Areata and Attention Deficit Hyperactivity Disorder
Alopecia Areata and Migraines
Androgenetic Alopecia and Sleep Disturbances
Frontal Fibrosing Alopecia and Rosacea
The Bidirectional Relationship Between Thyroid Disease and Alopecia Areata
Authors of a new study used a database to evaluate whether patients with alopecia areata or androgenetic alopecia were at increased risk for hypothyroidism and whether patients with hypothyroidism were at increased risk for alopecia areata or androgenetic alopecia. For studies in alopecia areata, 682 cases were compared to 361,140 controls. For studies in AGA, 195 cases were compared to 201,019 controls.
Interestingly, alopecia areata was associated with an increased risk of hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; P = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of alopecia areata (OR, 45.6839; 95% CI, 1.8446-1131.4271, P = 0.0196). However, no causal relationship was found between AGA and hypothyroidism.
Comment
This bidirectional relationship is important and enters into my clinical thinking almost daily. We all know that patients with alopecia areata have a greater chance of having hypothyroidism than an average person might have. What is not always appreciated is that patients with hypothyroidism are at increased risk for alopecia areata.
Another ‘bidirectional relationship’ to add to the list.
As an example, consider the 32-year-old woman with a complex clinical presentation. She has what appears to be diffuse, non-scarring alopecia, but nobody can’t quite figure out what’s going on with her hair loss. After reviewing her chart, you realize she has hypothyroidism. Of course, not everyone with hypothyroidism has alopecia areata but in this sort of a challenging case you must say to yourself… “Oh, I wonder if there’s any chance there is some autoimmune scalp disease going on, given this patient has hypothyroidism. Is it at all possible she has alopecia areata or scarring alopecia? Let me look again with my trichoscope, and if I still can’t solve the diagnosis, then I’ll consider a biopsy.”
The relationship between hypothyroidism and alopecia areata is interesting!
REFERENCES
Yang et al. Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study Front Endocrinol (Lausanne). 2024 Mar 18:15:1356832. doi: 10.3389/fendo.2024.1356832. eCollection 2024.
Is there an association between Narcolepsy and Alopecia Areata?
Narcolepsy is a sleep disorder that is characterized by excessive sleepiness, sleep attacks, sleep paralysis, hallucinations and, for some, the sudden loss of muscle control (cataplexy). The “classic tetrad” of symptoms is excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. The disease affects roughly 1 in every 2,000 people but can go undiagnosed for many years.
Narcolepsy is poorly understood. However, it is now recognized that there are two main forms of narcolepsy depending on whether the patient has cataplexy (which means Ioss of muscle control):
Narcolepsy with Cataplexy ("N+C" or type 1 form)
Narcolepsy without Cataplexy ("N-C" or type 2 form).
The "N+C" form (type 1 form) is now understood to be due to an autoimmune reaction that destroys the brain’s 70,000 hypocretin 1 and hypocretin 2-producing cells. Hypocretin is a chemical (neurotransmitter) in the brain that regulates “wakefulness.” Hypocretins 1 and 2 are also called orexin A and B. The N+C form (type 1) was recently reported to be associated with an increased risk of a variety of autoimmune diseases - including alopecia areata, thyroid disease and rheumatoid arthritis.
Narcolepsy may, therefore, be a true autoimmune disease. The recent discovery of a link between narcolepsy and a gene for a component of the T cell receptor supports this theory. A link to the HLA allele DQB1*0602 has been proposed.
The cause of the "N-C" form (type 2 form) remains poorly understood.
Reports of Narcolepsy in Alopecia areata
Some studies have suggested that sleep quality is similar in patients with alopecia areata compared to the general population. This is based on 2014 studies by Inui and colleagues published in the International Journal of Dermatology. However, these studies were small (105 patients) and could not capture rare associations. One such rare association may be narcolepsy.
Alopecia areata and Narcolepsy
Both type 1 and type 2 narcolepsy have been reported in association with alopecia areata. One of the first reports of an association between alopecia areata and narcolepsy occurred in 1992 in the Spanish language medical literature. This was a report by Dominguez Ortega in which three patients with alopecia areata were also described as having narcolepsy. The diagnosis in these three patients was made with a multiple sleep latency test. In 2010, Lloyd King and colleagues from Vanderbilt University reported two additional cases of narcolepsy seen in association with alopecia areata. Nigam and colleagues reported a male with type 1 narcolepsy.
Final Summary
Patients with narcolepsy may have an increased risk of alopecia areata.
References*
Nigam G, et al. Alopecia areata and narcolepsy: a tale of obscure autoimmunity. BMJ Case Rep. 2016.
Domínguez Ortega L. [Narcolepsy and alopecia areata: a new association?]. An Med Interna. 1992.
King LE Jr, et al. A potential association between alopecia areata and narcolepsy. Arch Dermatol. 2010.
Inui et al. Sleep quality in patients with alopecia areata: questionnaire-based study. Int J Dermatol. 2014.
Martinez-Orozco FJ et al. Long-Term Outcome of a Series of Patients With Narcolepsy Type 1 and Comorbidity With Immunopathological and Autoimmune Diseases. J Clin Med Res . 2022 Aug;14(8):309-314. doi: 10.14740/jocmr4758. Epub 2022 Aug 27.
New Studies Link Alopecia Areata to Eye Diseases
Patients with alopecia areata may have increased risk of several types of eye diseases - including retinal diseases. Three recent studies are important to reflect upon.
Ergin et al, 2015
A 2015 study set out to assess tear function and ocular surface pathologies in patients with alopecia areata. 32 patients with alopecia areata were compared to 20 age- and sex-matched healthy controls.
Dry eye disease (DED) was diagnosed in 27 (84%) of 32 alopecia areata patients and in only 3 (15%) of 20 controls, and there was a significant difference between the groups (P < 0.01).
Ting et al, 2021
A new study from Taiwan set out to examine the relationship between alopecia areata and retinal diseases. By examining information found in the National Health Insurance Research Database in Taiwan, the authors compared 9909 patients with alopecia areata to 99,090 match controls In this study, patients with alopecia areata had an approximately 3 fold greater risk of having any type of retinal disease ( adjusted hazard ratio (aHR) of 3.10 (95% confidence interval [CI] 2.26-4.26)
In terms of specific eye diseases, patients with alopecia areata had a 3.98 fold increased risk of retinal detachment, a 3.24 fold increased risk of retinopathy and a 2.45 fold increased risk of retinal vascular occlusion compared to patients without alopecia areata.
Thatiparthi A et al. 2022
Authors of a 2022 study also set out to evaluate the prevalence of various eye conditions in patients with AA. To do so, the authors analyzed electronic health records at a single academic center over a 10-year (March 2011-March 2021). In this study, there were 435 patients with AA and 35,349 healthy controls. As shown in the diagram below, a variety of eye diseases were found to be more common in patients with alopecia areata compared to controls. This included keratitis, iridocyclitis, scleral diseases, conjunctivitis, lacrimal disorders and disorders of eyelid inflammation.
Comment
These are interesting studies. Of course, we don’t fully understand why these links exist.
The authors point out that genome-wide association studies suggest that immune dysregulation in various inflammatory ocular conditions and alopecia areata likely share a variety of overlapping genetic factors, pathogenic inflammatory changes, and environmental factors.
More study is clearly needed but an important message here is that concerns raised by patients about eye symptoms need to be taken seriously and referral to eye specialists should be considered for patients with persistent and troublesome symptoms.
REFERENCE
Ting HC et al. Association between alopecia areata and retinal diseases: A nationwide population-based cohort study. J Am Acad Dermatol. 2021 Nov 1;S0190-9622(21)02735-3.
Thatiparthi A et al. Inflammatory ocular comorbidities in alopecia areata: a retrospective cohort study of a single academic center. J Am Acad Dermatol. 2022 Jun 16;S0190-9622(22)01009-X.
Ergin C et al. Ocular findings in alopecia areata.Int J Dermatol. 2015 Nov;54(11):1315-8.doi: 10.1111/ijd.12897. Epub 2015 Jul 3.
Hair Loss and Cardiovascular Risk
It’s quite a remarkable thing that patients with many types of hair loss are at increased risk for heart disease. Several good quality studies have emerged in the last 10 years showing us that androgenetic alopecia, alopecia areata, lichen planopilaris and folliculitis decalvans have some degree of increased risk of cardiovascular disease. For many of these conditions, it appears that patients in these groups have increased risks of metabolic syndrome which in turn influences some of this risk.
REFERENCES
Kim SR et al. Association of Primary Cicatricial Alopecia with Subsequent Cardiovascular Disease. J Invest Dermatol. 2023 Nov 19:S
Caro-Chang et al. Androgenetic alopecia and its association with metabolic syndrome: a systematic review and meta-analysis. Acta Medica Philippina 2019; 53: 122–131.
Qui Y et al. Systematic Review and Meta-analysis of the Association Between Metabolic Syndrome and Androgenetic Alopecia. Acta Derm Venereol. 2022 Feb 8;102:adv00645
Wu D-x, Wu L-f, Yang Z-x. [Association between androgenetic alopecia and metabolic syndrome: a meta-analysis]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2014; 43: 597–601 (in Chinese)
Conic RRZ et al. Prevalence of cardiac and metabolic diseases among patients with alopecia areata [published online August 11, 2020]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.16864 -
Joshi et al. Comorbidities associated with lichen planopilaris: a case-control study using the All of Us database. Int J Dermatol. 2022 Oct 2.
Conic et al. Exploring the association between lichen planopilaris, cardiovascular and metabolic disorders. J Eur Acad Dermatol Venereol 2021 Nov;35(11):e826-e828.
Bidirectional Relationships in Hair Loss
I’m fascinated by the epidemiology of hair loss - especially the so called “bidirectional” relationships that existing among various hair disorders.
What is a bidirectional relationship? Well, if patients with disease A are more likely to develop disease B and patients with disease B are also more likely to develop disease A… then you are talking about a bidirectional relationship!
Let’s look at some examples from the world of hair loss.
COMMON EXAMPLES OF BIDIRECTIONAL RELATIONSHIPS IN THE FIELD OF HAIR LOSS
Alopecia Areata and the Risk of Depression
Alopecia Areata and Attention Deficit Hyperactivity Disorder
Alopecia Areata and Migraines
Alopecia Areata and Hypothyroidism
Androgenetic Alopecia and Sleep Disturbances
Frontal Fibrosing Alopecia and Rosacea
It makes some sense that patients with alopecia areata might have higher rates of depression. But who would have thought that patients with depression are more likely to develop alopecia areata!
Yes, a bidirectional relationship!
The same goes for migraines and attention defecit hyperactivity disorder (ADHD). Surprisingly, patients with migraines and ADHD are more likely to develop alopecia areata.
Bidirectional relationships have been studied in androgenetic alopecia too. Males with sleep disorders seem to be at risk for androgenetic alopecia and males with androgenetic alopecia are at risk for developing sleep disorders!
Yes, more fascinating bidirectional relationships!
Finally, the scarring alopecia research world is slowly uncovering many fascinating bidirectional relationships. For example, it’s well known that patients with FFA are more likely to develop the skin disease rosacea. But who would have thought that patients with rosacea would have an increased risk of developing frontal fibrosing alopecia.
Many more of these bidirectional relationships exist. The speak to the complex and overlapping pathogenesis of many of these disorders.
References
Liamsombut et al. Sleep and Breathing. 2022
Müller Ramos P et al. J Am Acad Dermatol. 2021.
Ho HY et al 2021.
Moreno-Arrones OM et al. Clin Exp Derm 2019.
Vallerand et al. JAMA Dermatol. 2019.
FFA and Rosacea: What’s the link?
Rosacea in FFA Patients Linked to Greater Scalp inflammation, Greater Body Mass and Lower progesterone Levels
Several studies to date have suggested an association between the scarring alopecia frontal fibrosing alopecia (FFA) and the common dermatologic condition known as acne rosacea (or simply “rosacea”). How exactly the two are linked is not entirely clear.
Image of a woman with rosacea.
In 2019, Moreno-Arrones and colleagues conducted a multicentre case-control study and recruited 335 individuals with FFA to 329 patients who did not have FFA. Women with FFA were found to have a nearly two fold greater incidence of rosacea compared to women without FFA (OR = 1.91; 95% CI 1.07-3.39).
Porriño-Bustamante and colleagues also performed their own cross sectional study back in 2019 comparing patients with FFA to controls. In that study, the authors compared 99 women with frontal fibrosing alopecia to 40 controls. 62 % of women with FFA had rosacea compares to 30% of women without FFA. Women with more advanced stages of FFA were the most likely to report having rosacea compared with women with less advanced stages.
For women with FFA, three factors were found to be associated with a higher chance of having rosacea. In order of importance, these appeared to be 1) perifollicular erythema on the scalp 2) low serum progesterone levels and 3) higher body mass index. We still don’t know how these are related (and if giving progesterone or lowering weight affects rosacea in women with FFA).
A recently study by Liu et al estimated that women with FFA have a 2.46 fold increased risk of developing rosacea and the pooled prevalence was around 23 %. Muller Ramos found that women with rosacea have a 2 fold increased risk of developing FFA. This reinforces the bidirectional relationship between FFA and rosacea.
COMMENT
Women with FFA are at increased risk to develop rosacea and women with rosacea are at increased risk to develop FFA. We call this a ‘bidirectional’ relationship. However, what needs to be understood is whether “FFA associated rosacea” is precisely the same as rosacea in the general population. It seems to be but I’m not sure we know this in every single cass. Inflammation of the small vellus hairs of the face is known to be a part of FFA but is not so much a feature of typical rosacea in the exact same way. Pindado-Ortega showed in 2018 that most patients who were diagnosed with rosacea (28 of 35) ended up having the so called erythematotelangiectatic subtype of rosacea and 7 of the 35 had the so called papulopustular subtype. For now, rosacea in FFA is viewed as the same as rosacea in the general population. More studies will clarify the precise etiology.
It appears that FFA may be a negative prognostic factor in some ways although more studies are needed. Cid et al in 2020 showed that women with FFA plus rosacea were more likely to require systemic treatment than women without rosacea.
References
Moreno-Arrones OM et al. Risk factors associated with frontal fibrosing alopecia: a multicentre case-control study. Clin Exp Dermatol . 2019 Jun;44(4):404-410. doi: 10.1111/ced.13785. Epub 2018 Sep 26.
Pindado-Ortega C et al. Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship with rosacea. J Am Acad Dermatol . 2018 Mar;78(3):596-597.e1. doi: 10.1016/j.jaad.2017.09.004.
Walker JL, Robinson-Bostom L, Landow S. Four diseases, two associations, one patient: a case of frontal fibrosing alopecia, lichen planus pigmentosus, acne rosacea, and morbihan disease. Skinmed. 2016;14((3)):225–8.
Liu L et al. Association between frontal fibrosing Alopecia and Rosacea: Results from clinical observational studies and gene expression profiles. Front Immunol 2022 Aug 24:13:985081.
Müller Ramos P et al. Risk factors for frontal fibrosing alopecia: A case-control study in a multiracial population. J Am Acad Dermatol. 2021 Mar;84(3):712-718.doi: 10.1016/j.jaad.2020.08.076. Epub 2020 Aug 22.
Male Balding Is Associated with An Increased Risk of Sleep Disturbances
We spend approximately one-third of our life sleeping! Research over the last several decades has shown that poor sleep can affect many health issues including those related to cardiovascular, cerebrovascular, and autoimmune diseases.
Prior studies have sought to examine the relationship between sleep issues and male balding. A study in 2020 by Yi et al showed that males with more severe patterns of balding were more likely to have a range of sleep disturbances.
Today, I’d like to review a fascinating study from 2022 suggesting that a range of sleep disturbances are associated with male balding.
Liamsombut S et al. 2022
Using a case control design, authors set out to determine if sleep abnormalities were more common in males with mild, moderate and severe AGA compared to controls.
Study participants completed a standardized questionnaire that contained self-evaluated sleep measures, including Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and STOP-BANG questionnaire.
The Pittsburgh Sleep Quality Index is 19-item self-rated questionnaire and is used to determine sleep quality. It has 7 components including subjective sleep quality, sleep latency, sleep duration, habitual sleep effciency, sleep disturbances, sleep-promoting medication, and daytime dysfunction. The total PSQI score (called the 'global score’) ranges from 0 to 21. Poor sleep quality is indicated when the score is greater than 5.
The Epworth Sleepiness Scale measures average daytime sleepiness. The total ESS score ranges from 0 to 24 and a score of 11 or more indcicates excessive daytime sleepiness.
The STOP-BANG score is used to evaluate sleep apnea risk. Patients with a STOP-BANG score score of 0 to 2 are considered to be low risk for moderate to severe obstructive sleep apnea. Those with a STOP-Bang score of 5 to 8 are considered to be at high risk for moderate to severe OSA.
Results
There were 446 male participants in the study including 223 (50%) males in the AGA group, and 223 (50%) were in the control group. The mean age of the AGA group was comparable to the controls (54.9±13.9 vs. 53.6±10.5 years; p=0.238).
The rate of high blood pressure was significantly higher in the AGA group than in controls (32% vs. 19%; p=0.002). There were no differences between groups in body mass index, smoking, alcohol consumption or diabetes. There were no differences in the Pittsburgh Sleep Quality Index between groups or the Epworth sleepiness scores between groups. However, STOP BANG scores of 5 or more (high risk) were significantly more common in the AGA group (21% vs. 14%; p=0.044).
Multivariable logistic regression analysis revealed males with AGA were more likely to have high blood pressure (odds ratio [OR] =1.90, 95% confidence interval [CI]=1.16–3.11, p=0.011) and STOP-BANG score≥5 (OR=2.05, 95%CI=1.15–3.66, p=0.015).
The authors evaluated whether there were differences according to severity of AGA. Of 223 patients with AGA, 124 (56%) were mild, 56 (25%) were moderate, and 43 (19%) were severe. When further evaluating data according to severity of AGA, males with severe AGA were more likely to have three sleep abnormalities. These were: total sleep time≤6 h (OR=2.16, 95%CI=1.02–4.57, p=0.044), Pittsburgh Sleep Quality Index >5 (OR=3.72, 95%CI=1.42–9.72, p=0.008), and STOP-BANG score≥5 (OR=3.01, 95%CI=1.11–8.13, p=0.030).
Conclusions
The conclusion of these studies were that males with AGA were more likely to have sleep disturbances especially the risk for obstructive sleep apnea. This was based on the significant association with a STOP-BANG score of 5 or more. Males with AGA were also more likely to have high blood pressure. Patients with severe AGA patients appear to be at greater risk for having poor sleep quality and coexisting OSA.
The reasons for these links is not clear. It is generally proposed that poor sleep and sleep apnea drive metabolic and inflammatory issues that generally affect health and promote follicular microinflammation. However, the links are not clear.
References
Liamsombut S et al. Sleep quality in men with androgenetic alopecia.Sleep and Breathing. 2022 Apr 25.
Yi Y, Qiu J, Jia J et al (2020) Severity of androgenetic alopecia associated with poor sleeping habits and carnivorous eating and junk food consumption-a web-based investigation of male pattern hair loss in China.
Alopecia Areata May be Associated with High Frequency Sensorineural Hearing Loss
Several studies in the past have suggested an association between alopecia areata and hearing loss.
Alopecia areata is an autoimmune disease and follicular melanocytes are thought to be one of the important targets of the activated immune system. Melanocytes have a key role in the auditory (hearing) system, so it’s not surprising that researchers have examined the link between alopecia areata and hearing loss.
Sensorineural hearing loss (SNHL) is the most common type and accounts for the majority of all hearing loss in the general population. SNHL refers to any cause of hearing loss due to a pathology of the cochlea, auditory nerve, or central nervous system. In other words, sensorineural hearing loss results from damage to the hair cells within the inner ear, the vestibulocochlear nerve, or the brain's central processing centers
Lien KH et al 2023
In a new study, authors performed a systematic review using five case-control studies and one cohort study. The meta-analysis showed AA patients had significantly higher mean differences in pure tone hearing thresholds at 4000 Hz and 12000 to 12500 Hz. The meta-analysis also found a three fold increased odds for SNHL among patients with AA (OR 3.18; 95% CI 2.06-4.89).
The hearing loss was most marked at 12000 to 12500 Hz. However, among 250 to 8000 Hz, the range which most sounds of daily conversations occur, only 4000 Hz showed significant difference in the author’s meta-analysis.
All in all, the authors here concluded that alopecia areata is associated with an increase of SNHL, especially at high frequencies. The authors remind us that high frequency hearing loss is often neglected by patients but may present with tinnitus. The authors proposed that consultation with an audiologist or otolaryngologist (ear, nose & throat specialist) may be indicated if patients with alopecia areata present with hearing abnormalities such as hearing loss or tinnitus.
High frequency hearing loss is a common type of hearing loss in the general population.
Humans can hear sounds in the frequency range between about 20 Hz to 20,000 Hz. Difficulties hearing above 2000 Hz (2000 to 8000 Hz) is referred to as high frequency hearing loss. (To see if you can hear 2000 Hz sounds click here). About 1 in 7 people over 65 have sensorineural hearing loss. 90 % of people with hearing loss have the sensorineural hearing loss type.
What’s it like to have high frequency hearing loss?
Affected individuals may have trouble discriminating certain voices (children’s voices and some female voices), birds, animal sounds, beeps from phones and appliances, and sometimes door bells. Individuals with high frequency hearing loss may find it difficult to have conversations when there is a lot of background noise present. They have difficulty with certain letters including “S, H and F …and TH” Affected people have trouble conversing in restaurants and speaking with others at parties. Some patients also have tinnitus, which is often seen in those with sensorineural hearing loss.
Hearing aids can help high frequency hearing loss and are specifically designed for specific patterns of hearing loss.
REFERENCE
Seborrheic Dermatitis and Parkinson’s Disease
Parkinson’s disease is a complex neurodegenerative disorder. In Parkinson's disease, certain nerve cells inside the brain called neurons slowly break down or die. Many of the symptoms of Parkinson's are now known to be due to a loss of neurons that produce a chemical called dopamine. When dopamine levels decrease, the result is irregular brain activity and subsequently problems with movement and other symptoms of Parkinson's disease.
Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. Parkinson’s Disease has a prevalence of approximately 0.5–1% among those aged 65–69 years and prevalence rises to about 1–3% among those aged 80 years of age and older.
The symptoms of Parkinson’s disease generally develop very slowly over many years. Symptoms may differ slightly between people. Symptoms are often classified into two types - one type is referred to a ‘motor’ symptoms and the other type is referred to as non-motor symptoms.
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MOTOR SYMPTOMS OF PARKINSON’S DISEASE
People affected by Parkinson’s disease may experience:
Tremor. This tremor occurs mainly when the person is not moving. One type is of tremor is a tremor in the hands known as a pill rolling tremor.
Slow movements and reduced movement. This is known as bradykinesia (slow movement) and hypokinesia (reduced movement).
Stiffness of the limbs. (rigidity)
Problems with gait and balance. This is referred to as “postural instability.”
NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASE
In addition to these ‘motor’ symptoms that were described above, people with Parkinson’s disease may also have non motor symptoms. These symptoms include depression, anxiety, sleeping problems, loss of smell, apathy, hallucinations, constipation, orthostatic hypotension, and a variety of memory and thinking impairments. Other non-motor symptoms include pain, fatigue, low blood pressure, restless legs, bladder and bowel problems, skin and sweating problems, issues with eating, swallowing, saliva and dental health, issues with speech and communication, eye and foot care.
Diagnosis of Parkinson’s Disease
There is not a specific single test that allows one to diagnose Parkinson’s Disease. The diagnosis comes from a combination of information obtained from the history and physical examination. Features such are tremor, muscle rigidity, slowed movement (bradykinesia), poor balance, speech changes, changes in writing, altered automatic functions (like blinking, smiling and swinging the arms) will help the neurologist properly diagnose Parkinson’s disease. Generally speaking, the diagnosis of Parkinson’s diseaese is based on clinical symptoms with the criteria for a diagnosis requiring the presence of bradykinesia plus either tremor or rigidity to make the diagnosis.
Seborrheic Dermatitis (SD) and Parkinson’s Disease
The prevalence of seborrheic dermatitis is known to be increased in several neurological diseases including Parkinson’s disease. For example, the prevalence of SD in the general population is around 3-5 % whereas the prevalence of SD in patients with PD has been reported to range from 18.6% to 59%.
Seborrheic Dermatitis is Closely Linked to the Severity of Motor Symptoms
In one study in 2022 by Tomic and colleagues, the severity of a patient’s motor symptoms correlated with their likelihood to develop seborrheic dermatitis. In other words, patients with moderate-to-severe motor symptoms were more likely to develop seborrheic dermatitis compared to those with mild motor symptoms.
Reference
Fischer M, Gemende I, Marsch WC, Fischer PA. Skin function and skin disorders in Parkinson’s disease. J Neural Transm (Vienna) 2001; 108:205-213.
Patients with Alopecia Areata are at Risk For Heart Disease
Accumulating data in the past few years is teaching is that patients with several hair loss conditions may be at increased risk for cardiovascular disease. Certainly this seems to be the case for patients with alopecia areata, lichen planopilaris and androgenetic alopecia.
Conic and colleagues 2021 Study
A landmark study in 2021 is really important for us all to know. The study, published in the Journal of the European Academy of Dermatology and Venereology by Conic and colleagues, showed that patients with alopecia areata are at increased risk of certain cardiac and metabolic issues.
The study involved extraction of data from a large electronic database (the Explorys electronic aggregate database), which houses medical records data from more than 50 million patients across the United States. The researchers compared a group of patients with alopecia areata (n=33,130) to a group without AA (n=57,246,350).
Compared with control patients, patients with AA had elevated prevalence rates of several conditions including hypertension, diabetes, hyperlipidemia, coronary artery disease, atrial fibrillation and stroke.
Increased odds for metabolic disorders, coronary artery disease, atrial fibrillation and stroke.
In regression models, patients with AA had significantly increased odds for metabolic disorders, coronary artery disease, atrial fibrillation and stroke. The odds of myocardial infarction (heart attacks) was not significantly elevated in patients compared with control patients (OR, 1.04; 95% CI, 0.97-1.12)
The following table summarizes the magnitude of increased risk in alopecia areata patients compared to controls.
Summary
This is an important study and one of the largest studies to date examining the relationship between alopecia areata and cardiovascular disease. The evidence suggests that patients with alopecia areata are at increased risk for a variety of medical issues including hyperlipidemia, obesity, diabetes, coronary artery disease, atrial fibrillation and stroke.
The study was not designed to allow further investigation into these risks according to subtype of AA or AA severity so we can’t conclude from this particular study if risks are different in alopecia universalis compared to patchy alopecia areata. However, more recent studies have suggested that patients with alopecia totalis and universalis may have higher risks than those with patchy alopecia areata.
Further research may provide insight into how best to reduce this risk in certain patient subgroups.
REFERENCE
Conic RRZ et al. Prevalence of cardiac and metabolic diseases among patients with alopecia areata. JEADV 2021 Feb.
Are patients with Lichen Planopilaris at Risk for Thyroid Disease?
Meta-analysis suggests two fold increased risks of thyroid disease in patients with lichen planopilaris.
Lichen planopilaris (LPP) is a type of immune mediated scarring hair loss condition. Several previous studies have examined whether patients with LPP are at increased risk to develop thyroid disease compared to people who don’t have LPP.
Studies in the past have shown a variety of results. Some studies in the past have suggested that patients with LPP are at increased risk to develop hypothyroidism. Other studies have suggested there is really not much of an increased risk. One study even suggested a trend towards a reduced risk.
Joshi et al 2023
Authors of a new study set out analyze the association between LPP and hypothyroidism by performing a systematic review of all the published medical literature followed by a meta-analysis. This means the authors carefully review all prior studies and didn’t leave any relevant ones out.
The authors searched medical databases (EMBASE and MEDLINE) using the keywords “comorbidities,” “hypothyroidism,” “lichen planopilaris,” and “thyroid.” They included in their study all the case–control studies that examined the prevalence of LPP among cases and controls.
There were 7 studies that the authors uncovered. The authors found 4 studies that reported a positive, statistically significant associations between LPP and hypothyroidism. There were 2 studies showing a positive but statistically insignificant association and one study showed a negative, statistically insignificant association.
Overall, the meta-analysis showed an increased an approximately two fold prevalence of hypothyroidism in LPP patients compared with controls (OR = 1.75, 95% CI: 1.46–2.21, P = 0.001).
Conclusions
Patients with lichen planopilaris seem to be at increased risk to develop hypothroidism. This study reminds us all of the importance of testing thyroid levels in patients with LPP.
The reasons for the association are not clear and the study did not set out to search for a reason. It could be that patients with hypothyroidism and LPP share some sort of dysregulation of T cell or cytokine pathways.
We don’t know if the risk is going to be different in patients with more severe LPP than patients with less severe LPP or whether patients with different subtypes of LPP have different risk. For example, we don’t know if patients with the frontal fibrosing alopecia (FFA) type of LPP have different risk than classic LPP.
Overall, this was a nice study highlighting the increased risk of thyroid disease that is present in patients with LPP.
References
Joshi TP et al. Association of lichen planopilaris with hypothyroidism: a systematic review and meta-analysis. Int J Dermatol. 2023 Jul 10.23 Nov;62(11):e606-e608.
Androgenetic Alopecia: A Closer Look at the Heart Disease that Sometimes Goes Along with it
Evidence Points to an Approximately Three Fold increased Risk of “Metabolic Syndrome” for Patients with Androgenetic Alopecia
“Metabolic syndrome” is a term that refers to the group of abnormalities that increase the risk for cardiovascular disease. When you say that a patient has “metabolic syndrome” you are saying that they have one or more of issues such as high blood sugars, high cholesterol, high blood pressure and central obesity. It’s been clear for many years that patients with androgenetic alopecia are at increased risk for metabolic syndrome.
To date, there have been several studies teaching us that patients with androgenetic alopecia are at risk for metabolic syndrome. In fact, studies go back to 1972 when a landmark study by Cotton and colleagues published in the British Heart Journal showed that males with balding had an increased risk of heart disease. So we’ve realized for some time that hair loss is associated with heart disease!
Are patients with androgenetic alopecia at risk for metabolic syndrome?
Three meta-analyses in the past showed that patients with androgenetic alopecia are at risk for metabolic syndrome. This includes nice studies by Wu and colleagues in 2014, Caro-Chang and colleagues in 2019 and Qui and colleagues in 2022. The study by Wu et al showed that patients with AGA had a 2.70 fold increased risk, and the study by Caro-Chang et al showed the risk was 2.59 fold. A recent study by Qui et al put the risk at 3.46 fold.
Conclusion and Comments
In conclusion, it’s quite clear that our patients with androgenetic alopecia are at risk for heart disease. Studies have showed that risks seem even greater in our female patients who are experiencing androgenetic alopecia than our male patients and greater in specific groups such as early onset AGA and patients with African and Asian ethnicity.
“Metabolic syndrome” is a nice term. But it’s a bit of a “euphemism.” In the English language, a euphemism is a word or term that is used to soften a harsher term. For example, instead of saying someone is sick, we might say he or she is ‘under the weather.’ Instead of saying a care is ‘used’ we say that a car is ‘pre-owned.’
In my opinion, the term metabolic syndrome is sort of like a euphemism. When we learn that AGA is associated with an increased risk of ‘metabolic syndrome’ we don’t tend to do very much about it! If we were to say that our patients with AGA are more likely to die early from heart attacks and strokes, perhaps we’d be more worried.
Overall, these studies are such an important reminder that we need to be talking about risks for metabolic syndrome in our patients with AGA. We need to make sure blood pressure gets measured in all our patients with AGA, screening for diabetes and insulin resistance gets done and that weight is measured often and patients are encouraged to keep weight in a healthy range.
My Own Guidelines for Monitoring the Patient with AGA
We do not yet have screening guidelines in the world for how best to monitor males and females with AGA. We now know with great confidence that males and females with androgenetic alopecia have an increased risk of developing metabolic syndrome and cardiovascular disease later in life. There’s just no doubt! I feel strongly that our medical community has neglected this issue but nevertheless I have guidelines in my clinic that we feel are appropriate first steps. In my clinic, I recommend the following:
1. Encouragement of healthy eating and diets rich in antioxidant rich fruits and vegetables.
2. Encouragement of active lifestyles with 150-300 minutes of moderate physical exercise weekly (or 75-150 minutes of more vigorous aerobic activity).
3. Smoking cessation strategies for all smokers and encouragement to not begin smoking.
4. Blood pressure measurements at baseline and then every 2-3 years by the family physician. Encourage of home monitoring in those with borderline measurements. Treatment of hypertension with lifestyle and pharmacological means as recommended by current evidence based guidelines.
5. Measurement of cholesterol levels at baseline and then every 3-5 years if normal at baseline. Treatment of abnormal cholesterol level according to current evidence based guidelines.
6. Fasting glucose insulin and hemoglobin A1c levels at baseline and every 3-5 years if normal at baseline. Consideration of further tests for insulin resistance as appropriate.
7. Weight and height measurements yearly and evidence based weight reduction strategies if weight is found to be in the overweight or obese ranges.
Are we not ready yet as a medical community to make this the standard of care? We are now approaching 50 years since a link between heart disease and hair loss was first uncovered. It’s about time.
REFERENCES
Caro-Chang et al. Androgenetic alopecia and its association with metabolic syndrome: a systematic review and meta-analysis. Acta Medica Philippina 2019; 53: 122–131.
Qui Y et al. Systematic Review and Meta-analysis of the Association Between Metabolic Syndrome and Androgenetic Alopecia. Acta Derm Venereol. 2022 Feb 8;102:adv00645
Wu D-x, Wu L-f, Yang Z-x. [Association between androgenetic alopecia and metabolic syndrome: a meta-analysis]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2014; 43: 597–601 (in Chinese)
Risk of Cardiovascular Disease in Patients with Scarring Alopecia
Males with Primary Scarring Alopecia are At Particularly Increased Risk of Heart Disease
Men with primary scarring are at a higher risk of developing cardiovascular disease, coronary artery disease or stroke, according to a new study conducted by researchers from Korea. The study involved 406,016 patients, 7,986 of whom had primary scarring, 78,590 who had non-scarring, and 319,440 controls who did not have hair loss. The participants were enrolled from 2013 to 2020 and were tracked until Dec 31 2020. The study included patients with various types of scarring, including pseudopelade of Brocq (PPB), lichen planopilaris/frontal fibrosing alopecia (LPP), folliculitis decalvans (FD), dissecting cellulitis (DC). A category called cicatricial alopecia unspecified (CAU) was also included in this study.
Patients with primary scarring alopecia ranged in age from 36.3 to 65.4 years, with 65.4 percent being male. The patients with PCA had more underlying disease and higher body mass index (BMI) and FSG than those in the control group.
Patients with Scarring Alopecia have increased Risk for Heart Disease
Patients with primary scarring alopecia had a higher risk of cardiovascular disease (aHR 1.18; 95% CI 1.01-1.38) and coronary heart disease (aHR 1.26; 95% CI 1.02-1.55) compared to controls after fully controlling for potential confounders (such as age, sex, household income, smoking, alcohol intake, physical activity, systolic blood pressure, fasting serum glucose, total cholesterol, and Charlson comorbidity index).
Risks for Folliculitis Decalvans Patients
Compared to controls, patients with folliculitis decalvans had a higher risk of stroke (aHR 1.39; 95% CI 1.05-1.84) and cardiovascular disease (aHR 1.29; 95% CI 1.04-1.61).
Risks for Lichen planopilaris/FFA Patients
Patients with lichen planopilaris (aHR 1.93; 95% CI 1.07-3.49) had an increased coronary heart disease risk compared to controls.
Risk by Sex
When sex was taken into consideration, it was discovered that men with primary scarring alopecia were far more likely than women to experience cardiovascular disease coronary heart disease and stroke. In fact, men were primarily at risk.
Conclusion
Overall, the researchers discovered that, in comparison to controls without alopecia, patients with primary scarring alopecia had a higher risk of cardiovascular disease. In particular, among the subtypes of scarring alopecia, FD or LPP was substantially related with a higher risk of cardiovascular disease, coronary heart disease or stroke. Pseudopelade of Brocq and dissecting cellulitis did not seem to have any risk.
The precise cause of increased risk is unknown in patients with scarring alopecia. One possible common link has been suggested to be faulty lipid metabolism. It is well known that lipid metabolism dysregulation may be an important in the pathways that lead to scarring alopecia.
These findings are significant because they imply that we should consider more carefully how to lower the risk of cardiovascular disease in patients wth scarring alopecia. This may be especially important for males who are more vulnerable.
STUDY REFERENCE
Kim SR et al. Association of Primary Cicatricial Alopecia with Subsequent Cardiovascular Disease. J Invest Dermatol. 2023 Nov 19:S
Listening to the Patient
This week in the Evidence Based Hair Fellowship we reviewed 10 key questions that must be asked when evaluating patients. There are a variety of wonderfully powerful questions that can prompt the hair specialist to think of diagnoses and comorbid medical conditions that otherwise would be missed. A simple “yes” do a question about body hair loss can send the hair loss specialist down a completely different path.
WILLIAM OSLER AND THE POWER OF LISTENING
William Osler was a Canadian physician and one of the 4 founding professors of John Hopkins Hospital . He was not only a physician but an educator, philosopher (and apparently a wonderful practical joker too). He is often honoured with the title as the “Father of Modern Medicine.” Hs teachings and words have influenced the practice and careers of countless physicians around the world.
Sir Osler once provided advice about listening to patients:
Sir Osler’s advice is too often forgotten in era of fancy diagnostic tests. The patient’s story still remains a powerful tool when tough diagnoses need to be made. If I practiced hair loss medicine without the chance to speak to the patient, I’d certainly make a great number of errors in diagnosis. That’s even with all the dermatoscopes I own, the array of tests I have at my disposal, and even with the wonderful dermatoapthologists that I’m so lucky to work with.
The patient’s story is important!
Week 1 of the EBHF is Underway!
The Evidence Based Hair Fellowship (EBHF) is officially underway! Congratulations to all our incredible participants!
The first week, the first assignments, the first quizzes and the first logins to the Donovan Hair Academy Website - many “firsts” this week.
Welcome to our EBHF Participants !
Just one week to go until I welcome 100 incredible hair loss specialists for a 20 month journey through the Evidence Based Hair Fellowship (EBHF) training program.
Participants meet weekly online for a challenging but fun program that stimulates the brain to think and problem solve like an expert. The journey starts off with 7 weeks of some of the most important material - the basic principles of hair loss diagnosis and treatment.
We then journey through “blocks” of 1-2 month duration dedicated to subjects such as androgenetic alopecia, telogen effluvium, alopecia areata, scarring alopecia, hair shaft disorders, psychodermatology, traction alopecia, contact dermatitis, cancer, dysesthesias, hair transplantation and pigmentation. We discuss hair loss in children and infants and adults and pregnancy and older age.
We challenge ourselves each week with quizzes and tough cases and assignments. In Aug 2025, we reach the finish line with a new set of skills to last a lifetime !
I am looking forward to meeting this amazing group of EBHF participants!
Just one week to go until I welcome 100 incredible hair loss specialists for a 20 month journey through the Evidence Based Hair Fellowship (EBHF) training program.
Participants meet weekly online for a challenging but fun program that stimulates the brain to think and problem solve like an expert. The journey starts off with 7 weeks of some of the most important material - the basic principles of hair loss diagnosis and treatment.
We then journey through “blocks” of 1-2 month duration dedicated to subjects such as androgenetic alopecia, telogen effluvium, alopecia areata, scarring alopecia, hair shaft disorders, psychodermatology, traction alopecia, contact dermatitis, cancer, dysesthesias, hair transplantation and pigmentation. We discuss hair loss in children and infants and adults and pregnancy and older age.
We challenge ourselves each week with quizzes and tough cases and assignments. In Aug 2025, we reach the finish line with a new set of skills to last a lifetime !
I am looking forward to meeting this amazing group of EBHF participants!
If you have any questions about our courses, webinars or the Evidence Based Hair Fellowship, please contact the academy for more information at info@donovanhairacademy.com
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