Diagnosis & Treatment Scarring Alopecia

Thank you very much for the introduction, and it's my pleasure to join you today to talk about one of my favorite subjects, and that's the diagnosis and treatment of scarring alopecia. We are learning a lot over the last several years about how these conditions present, and how they present in different people, but more importantly, what are the optimal treatments for these challenging conditions.

And so today, I'd like to help you understand what are the features that we draw from a patient's history, as well as their examination, which leads us to the diagnosis of scarring alopecia, and how do we do this quickly. I'd also like to review trichoscopy or dermoscopy, and how we use a handheld dermatoscope to actually diagnose scarring alopecia and to evaluate their activity. And then, of course, I'd like to review a few treatments. What are some of the topical treatments, injection-based treatments, as well as systemic treatments for scarring alopecia? I don't have any conflicts of interest about anything I'm going to speak to you about today.

As you all know, one of the challenges of diagnosing scarring alopecia, and diagnosing hair loss in general, is the perceived time that it takes to evaluate hair loss properly. The reality is that one can generally very quickly identify a patient with a potential scarring alopecia based on a limited number of questions, and I'd like to review some of these today with you all. Six of these women in this photograph have central hair loss, but only one of them has scarring alopecia. And so, what are some of the features that we can identify on history that really allow us to have a raised suspicion for scarring alopecia? We're going to talk about that today, because I think this is one of the most important points of today's lecture. Is that patients that present with hair loss associated with itching, burning, and pain, or hair loss in particular regions of the scalp, these patients need to be considered to have a high index of suspicion for scarring alopecia.

By way of review, let's review what's meant by primary scarring alopecia and secondary scarring alopecia. Most of what we see in clinic are the primary scarring alopecias, like in lichen planopilaris, frontal fibrosing alopecia, CCCA, folliculitis decalvans. These are primary scarring alopecias. And by primary scarring alopecia, what we mean is that the immune system is targeting the hair follicle. And as you can see in this diagram, this is a diagram of the skin with a hair follicle in the middle, and there's some black dots right in the middle of the hair follicle. This is indicating that the immune system is targeting the hair follicle. The immune system somehow recognizes antigens in the hair follicle, and this is what it's attacking. In secondary scarring alopecia, the hair follicle is an innocent bystander. There's something in the skin, a generalized process, whether it's an infection or a burn, that's destroying everything in its path, and this leads to loss of the hair follicle as well. So, when primary scarring alopecia, the hair follicle is the primary target of the immune system. Where some secondary scarring alopecia, the hair follicle is an innocent bystander.

Here's some secondary scarring alopecia. We don't see these all that commonly in the clinic, but we do see them, of course. The patient on the left has herpes zoster. She had an infection with shingles at one point on the scalp, led her to develop hair loss, and led her to develop permanent hair loss in this area, accompanied by pain. And this is an example of herpes zoster. The photograph on the right is something you may or may not have seen, but we're seeing it much more commonly, and that's a secondary scarring alopecia from hair highlighting. This is a particular interest in the clinic. From a research perspective, I'm not sure why this is increasing worldwide, but I do believe that it is. The typical scenario of a secondary scarring alopecia from hair highlighting is a story that goes somewhat like this. A patient enters a hair salon. She or he is about to have their hair highlighted. The hair highlighting agent is put on the scalp. Within several seconds to minutes, the patient complains that there's burning on the scalp. She complains that something is not right. "Get it off! Get it off!" The agent is removed, and a few days later, the patient develops hair loss in this area, accompanied by pain, burning, itching, and then develops permanent hair loss in the area. That's a secondary scarring alopecia from hair highlighting.

So, both primary and secondary scarring alopecias lead to permanent hair loss. They have different mechanisms, but when you look up close at the level of the scalp, both primary and secondary scarring alopecias are associated with loss of the follicular opening, or loss of the follicular ostia. So, on the left, we have a photograph of alopecia areata. This is an up-close dermoscopic image of the scalp in alopecia areata. Alopecia areata, as you all know, is a non-scarring alopecia. And when you look at this photograph, you see that the follicular openings are present. You see all of these little yellow dots. We can see some exclamation mark hairs here as well. In the photograph on the right, we see a scarring alopecia. This is a typical example of pseudopelade of Brocq, but it could be any scarring alopecia. We do not see the follicular openings. They are absent, and this is very typical of what we see in scarring alopecia. It's this loss of the follicular opening.

Here's a patient with lichen planopilaris. Again, the scalp looks a little bit different than the previous photograph, but the dermoscopic image shows scale around these hairs, a whitish scale, which we call perifollicular scale, or follicular hyperkeratosis, which we'll see in just a few minutes. But we do not see these follicular openings or these pores.

The hair follicle contains many components. This is a schematic diagram which shows a hair follicle with its sebaceous gland at the top, and just beneath the sebaceous gland is the so-called bulge region. And at the very bottom, we have the germinal matrix, which gives rise to new hair follicles. And it was really George Cotsarelis, who is the chair at Penn, who many years ago, in 1990, discovered where hair follicle stem cells lived. And this data showed that hair follicles reside in the bulge. This is a very key region where the hair follicles and the hair follicle stem cells reside. And a lot of technology nowadays, and a lot of the understanding of hair follicle biology, resides in understanding these so-called hair follicle stem cells. And as we'll see in just a few minutes, it is the immune system's attack on this region of the hair follicle, in the bulge and the sebaceous gland, that is a primary component of how scarring alopecia is developed.

So, with scarring alopecia, we actually see in many of these that the inflammation is located in the upper region of the hair follicle, in this so-called hair follicle bulge region, of the isthmus and the infundibulum. The infundibulum is the upper region of the hair follicle from the skin surface to the opening of the sebaceous gland. And then from the opening of the sebaceous gland to where the erector pili muscle inserts, that is the isthmus. It's in this region of the isthmus and the infundibulum where the inflammation is present in scarring alopecia. The inflammation in this region attacks and destroys hair follicle stem cells, and this limits the ability of the hair follicle to regenerate.

When we look at alopecia areata, which, as I mentioned, is a non-scarring alopecia, we see that the inflammation is located deep down in the bulge region of the hair follicle. The hair follicle stem cells are not affected. And therefore, if we can get rid of this inflammation in the bulge region, we can give rise to new hair follicles, because these stem cells can then give rise to new hair follicles. And so, a key understanding of the difference between scarring alopecias and non-scarring alopecia comes down to this understanding of the location of the inflammatory infiltrate, or the inflammation. Inflammation is in the isthmus in scarring alopecia. And many of these non-scarring alopecias, the isthmus does not contain inflammation.

The other thing I want to point out, which is a very important concept to understand for all of us here today, is that next to the hair follicle bulge is the sebaceous gland. And in diagrams like this that we show for the hair follicle, we often show the sebaceous gland flapping at the side, far away from the sebaceous gland. The reality is that the sebaceous gland and the bulge region are very closely located. And the inflammation in these scarring alopecias that targets the bulge region also targets the sebaceous gland. And in fact, it's thought that inflammation in the sebaceous gland is one of the earliest steps in a scarring alopecia. And so, sebaceous glands are a key target in scarring alopecia. And I'll explain now why this is such an important point for us to understand.

You know, we often see a lot of cases that are challenging, difficult diagnostic cases. Patients have hair loss accompanied by itching and burning and pain. Some patients have biopsies showing perifollicular fibrosis or scarring, and they're referred in to me with the question, "Is this a scarring alopecia?" And a surprising number of these patients, despite having scarring on biopsy, and even inflammation when biopsied, don't end up having a final diagnosis of scarring alopecia. And one of the things that we ask in patients with these challenging clinical presentations is the following: It would be great to be able to ask, "Are the same number of stem cells present in that hair follicle biopsy as well?" Originally, because clearly, if there was a reduction in hair follicle stem cells, this would be an indication that, "Hey, maybe this is a scarring alopecia." We don't know how to do that in the present day and age. We don't know how to assay hair follicle stem cells and determine if it's any different than it used to be. But what we can do is we can look at the density of sebaceous glands. And we can ask the pathologist, in these challenging cases, to comment on the density of sebaceous glands. And in situations where there's no reduction in sebaceous glands over an extended period of observation, one must consider the possibility that this may not be a scarring alopecia, because one of the features that we see in scarring alopecia, maybe not early on, but especially in moderately advanced stages, is a reduction in sebaceous glands.

So, consider this patient, at the age of 55 years, who presents to me with hair loss. He has itching and burning in his scalp. He has a red scalp. When you look up close, this is a trichoscopic image of his scalp. You can see scale around the hair follicles. The scalp is red. He's had several biopsies. In fact, he's had multiple biopsies. They have shown fibrosis around the hair follicles, so an evidence of a scarring type pattern. There are lymphocytes in the isthmus, so there's inflammation in the upper region of the hair follicle. And in fact, all of his biopsies show the same finding: inflammation and perifollicular fibrosis. One of the questions that I have in this case, because something did not seem right in his clinical presentation, is, "Is the inflammatory infiltrate attacking the hair follicle, causing necrosis or a so-called lichenoid change around the hair follicle in the outer root sheath?" which many of us here in the room know to be a key feature of lichen planopilaris. But the other thing that I ask in these challenging cases is, I ask the pathologist to comment on the density of sebaceous glands. And what we see in these challenging cases, when we go back, is that in many of these cases, the sebaceous glands are not altered. Sebaceous glands are preserved. No loss. Biopsy two: sebaceous glands are preserved. No loss. Biopsy number three: sebaceous glands are preserved. No loss.

So, when a patient who has been followed for several years with multiple biopsies showing inflammation and scarring, but no lichenoid change in any biopsy, and no loss of sebaceous gland in any biopsy, is this likely to be a scarring alopecia? It's possible, but not likely. My diagnosis in this patient was androgenetic alopecia along with seborrheic dermatitis, along with a scalp dysesthesia. Scalp dysesthesia are these clinical phenomena where patients develop symptoms of itching and burning and pain and tenderness. They may have hair loss from other reasons, but we have to be careful in patients with scalp symptoms to immediately cause them to have a diagnosis of a scalp dysesthesia.

So, in this patient with genetic hair loss and seborrheic dermatitis and a scalp dysesthesia, what is my approach? Well, my approach is to treat his androgenetic alopecia. In this case, we decided on treatment with finasteride. To treat his seborrheic dermatitis, and there are many options for that, of course, including anti-fungals. And I treated scalp dysesthesia with gabapentin in this case. And this treatment protocol for him led to a resolution of his symptoms and an improvement in his hair density. And over a period of extended observation, there's been no further hair loss, and his scalp symptoms have abated. And so, this would be very unusual in a scarring alopecia for this particular treatment protocol to actually stop his hair loss and regrow it. And so, this is further confidence that in this patient, the correct diagnosis is not a scarring alopecia.

So, how do we classify these so-called primary scarring alopecias? Well, this is very important for us to understand this particular table. And in 2001, a number of physicians, mostly dermatologists, got together at Duke University in an attempt to better classify these scarring alopecias. There are many, many scarring alopecias, but in the present day and age, we classify them in a fairly simple way. We classify them according to the predominant inflammatory infiltrate on biopsy. So, if there's a lot of lymphocytes on biopsy, we call it a lymphocyte-associated scarring alopecia. If there's a lot of neutrophils, we call it a neutrophil-predominant scarring alopecia. And if there's a mixed bag of neutrophils, plasma cells, lymphocytes, we'll call it a mixed infiltrate. Things like lichen planopilaris, frontal fibrosing alopecia, CCCA, these are our classic lymphocyte-associated scarring alopecias. Folliculitis decalvans and dissecting cellulitis are our neutrophil-associated scarring alopecias. And acne keloidalis nuchae, erosive pustular dermatosis, this is our mixed scarring alopecia.

And we're going to talk about this. One of the things that I want to point out to you before we dive deeper into looking at these various scarring alopecias is a very important study by Paradi Mirmirani, who many of you know is in California and spends time at UCSF. And this study by the UCSF group is a very important study. And what this study showed is that it's very challenging for a pathologist to differentiate between some of these lymphocyte-associated scarring alopecias, and then to differentiate among some of these neutrophil scarring alopecias. And what I mean by this is, if you give world-class pathologists, like we have in this study, Tim Mikkalmon, John Heading, if you give these world-class pathologists biopsies of lichen planopilaris and frontal fibrosing alopecia, and you ask them, "Is this lichen planopilaris or frontal fibrosing alopecia?" they may not be able to tell them apart. There may be features, of course, where in lichen planopilaris, we have more inflammation, and in frontal fibrosing alopecia, FFA, we often have more apoptosis than in lichen planopilaris. But the reality is, many of these lymphocyte-associated scarring alopecias, we can't tell apart. Similarly, in some cases of folliculitis decalvans and dissecting cellulitis, it can be challenging to tell apart. If the inflammation is deep, we might say it may be consistent with dissecting cellulitis. If the inflammation is higher, folliculitis decalvans. But we are still limited in the present day in understanding how to fully identify conditions. And so, if I have a patient with frontal fibrosing alopecia, and I send in the biopsy, and I don't give any information to the pathologist, he or she may write back, "This is a lymphocyte-associated scarring alopecia, consistent with lichen planopilaris." If I say to the pathologist, "Dear pathologist, I think this is frontal fibrosing alopecia," the pathologist may then write, "Lymphocyte-associated scarring alopecia, consistent with the clinical assumption of frontal fibrosing alopecia." So, the information we give as clinicians is essential to the pathologist rendering their opinion about specific diagnoses.

So, how do we approach scarring alopecia? Well, everything is potentially important. And the one thing I enjoy about hair loss is pulling all that information that can be relevant to a patient's hair loss. The medications they're on, the stresses they experience, the foods they eat, the surgeries they've had. All of these are potentially relevant. But there are four particular things that I want to know about with every patient, because these four pieces of information are absolutely essential in terms of rendering my index of suspicion for scarring alopecia. I want to know about the scalp symptoms. Is there any itching, burning, and pain? I want to know about hair loss and shedding. Is the patient shedding more than normal? I want to know about the speed of their hair loss, and I want to know about where on the scalp their hair loss is occurring. And I refer to these as the four S's. And when I've worked with residents in clinic and fellows in clinic, and they come out of a room after seeing a patient, there's endless amount of information that they could potentially share with me. I want to know these four S's, because these are the things that help me to decide what diagnosis could be present.

A 48-year-old male with moderately fast hair loss with burning in the scalp, who may or may not have shedding, but whose crown is involved as the site, and who has blood on his pillow when he wakes up in the morning. This person has folliculitis decalvans until proven otherwise. A 39-year-old woman with afro-textured hair, who has pins and needles in the center of the scalp, maybe a little bit of shedding, and who's losing hair fairly rapidly. She has CCCA until proven otherwise. These four S's are extremely valuable. And at first glance, they seem a little bit too easy. But over time, I've come to realize that these are extremely valuable in terms of deciding who gets a biopsy and where a biopsy is unlikely to render useful information.

Consider these two patients. The patient on the left presents with central hair loss. The patient on the right presents with central hair loss. The patient on the left doesn't really have much in the way of symptoms. The patient on the right has itching and burning. She has shedding. She's uncomfortable. And when you look up close, you see redness around some of the hairs in the patient on the right. And a biopsy shows she has lichen planopilaris. Clinically very similar, but it's the scalp symptoms, her information, and of course, her trichoscopy that prompt us to consider a biopsy.

This is a very simple sketch. It's a very skillful sketch, simple sketch that I often draw on the hallway when working with physicians. And it's simple, but it's very valuable. It shows some of the anatomic regions that we need to be thinking about when we're diagnosing scarring alopecia. A 62-year-old woman who presents with hair loss along the front of her scalp, and it's receding back, back, back, back, back. She may tell you that her father had the same pattern of hair loss with recession. But this is frontal fibrosing alopecia. In a high percentage of cases of marked frontal hair loss, LPP, lichen planopilaris, pseudopelade, CCCA, these affect the central scalp. Of course, lichen planopilaris can affect other areas, but the central scalp is often affected in these areas. Folliculitis decalvans often affects the crown. It can affect the frontal scalp, it can affect other areas, but it commonly affects the crown. And other scarring alopecias like acne keloidalis, nuchal, affect the back of the scalp. And so, keeping these anatomic locations in mind is very helpful as we approach a patient.

And so, when I see a patient, I want to think about these four S's. But they don't want to know where the hair loss is. And I want to know what's happening to the hairs. I need to see the scalp, and I need to see what's happening around the hairs. And there's no better way to do that than with the dermatoscope. And I've come to realize over the last few years that a dermatoscope is extremely valuable to my clinic. And on days where I have left my dermatoscope somewhere else, or I've not charged my dermatoscope, I feel at a loss. The dermatoscope is absolutely essential to the proper evaluation of hair loss. And over time, one can become quite proficient at trichoscopy. And so, we'll review some of these key trichoscopic features today. And there's no need to fear trichoscopy.

The pull test is important. And so, when I see a patient with hair loss, I may pull hairs gently from the scalp. The thing that's important about the pull test is that if one extracts hairs from the scalp that are anagen hairs, meaning you remove it from the scalp and you see that there's an external root sheath around these hairs, as you can see on this far right picture, this is abnormal. The only time that we remove anagen hairs that look like this from the scalp is in a scarring alopecia. And one of the comments that we often have, I often have, is what about loose anagen syndrome? The hair that's removed in a patient with loose anagen syndrome, which is a condition common in children, doesn't look like this. The root sheath has pushed down like a crumpled sock, as you may recall, and it doesn't look like a relatively normal appearing hair. And for the most part, the only time that you see true anagen hair extracted is in a scarring alopecia. You can have telogen hairs that have crust around them. You can have telogen hairs with scale around them, and they can fool you into thinking it's an anagen hair. And so, it's helpful to look under a microscope. It doesn't take a lot of time. Even your dermatoscope can be helpful, but you can simply put a hair between two glass slides. You don't have to put any mounting media on it, and you can look under the microscope and you can determine if it's a true anagen hair.

The other important thing to comment on is the biopsy. It's really important. And it may be obvious, but we need to have a hair in a biopsy if we're going to perform a scalp biopsy. And the key question is, where am I going to biopsy? Well, if using your dermatoscope, you see an area with what you believe is the key morphologic feature, you see scale around the hair and redness around the hair, and you think it's lichen planopilaris, that's a great place to biopsy. If you think your patient has folliculitis decalvans, and you see an area with crusting or pustules, that's a great place to biopsy. But if you're not sure, another great place is where the patient has symptoms. So, I often ask patients, "Where do you have the most itching or burning?" "Right here, doc." That's a great place to biopsy. If you're not sure where high-yield locations are, the biopsy should be four millimeters. Why? Well, this is an adequate size to assess histopathology, but also there's some very standard measurements that your pathologist, if they're familiar with hair pathology, is looking for, including certain hair counts, the number of hairs per cross-sectional area. So, they're expecting a four-millimeter, a four-millimeter punch.

The biopsy should be deep. And so, you can see that this particular biopsy extends deep to the fat. The reason this is important is certainly in some challenging conditions, you really want to see what's happening in the subcutaneous fat and deeper. In challenging cases, you really want to see what's going on deep down. Dissecting cellulitis would be a good example. Some of the panniculitis. You really want to see what's happening deep down. So, biopsy in the biopsy.

So, let's talk a little bit about these scarring alopecias. So, we're going to start with the so-called lymphocyte-associated scarring alopecias. These are the most common by far. It's much more common to see a patient in clinic with lichen planopilaris or CCCA or FFA than folliculitis decalvans or dissecting cellulitis.

Here's a patient. She's 69. She's quickly losing her hair. She has scalp itching. Her scalp is tender. It hurts when she moves her hair around. When you look up close, you see this. You see definite areas of scarring. There's no follicular openings present. In the middle of this photograph, you see scale around some of the hairs. You see redness around some of the hairs. When you look at other areas, you see a large number of hairs with just single hairs, one hair strand coming out of these pores, and you see scale around some of these hairs. This blue circle is my pen mark. I'm about to do a biopsy. This is a very typical trichoscopic image of lichen planopilaris with single hairs and perifollicular scale and perifollicular erythema. We do a biopsy. We see a feature like this. And that is your eye immediately catches that there is inflammation around these hairs. There's a dark blueness surrounding these hair follicles. That is a reminder to us all that these are primary scarring alopecias. The immune system is targeting these hair follicles. The immune system is not randomly in this biopsy site. The immune system is accumulating around hair follicles. There's also inflammation in the skin. There's lichen planus happening at the level of the epidermis. And even at a low-power magnification, an expert pathologist would be very suspicious of lichen planopilaris. We often see this separation or this clefting between the outer root sheath and the dermis. We see this perifollicular fibrosis surrounding the hair follicles. And in the outer root sheath of the hair follicle, we see necrosis. We see apoptosis. We see this lichenoid change. This lymphocyte-predominant scarring alopecia is present. And this is a very classic photograph of lichen planopilaris.

Lichen planopilaris is a condition of middle age. It typically presents between 40 and 60. These are averages. You could have lichen planopilaris at 20. You can have lichen planopilaris at 68. There are many cases of lichen planopilaris that we see in children. And in many of these cases, we have to actually consider a number of genetic conditions rather than true lichen planopilaris. So, I'm always a little suspicious when we've diagnosed lichen planopilaris in a 7 or 8-year-old. It can't occur, but we have to think about some of these genetic entities. LPP appears to be more common in females. Certainly, females present to clinic more often and are diagnosed with LPP. And lichen planus can be present in other regions of the skin in about 50% of cases. And this may be lichen planus of the nail, lichen planus of the gingiva, of the vaginal mucosa. We have to be aware of this. This is a patient with lichen planopilaris, and when we look up close at the beard, we see that there is lichen planopilaris of the beard hair follicles as well. A patient with typical lichen planus of the nail with this vertical ridging and this V-shaped separation at the end. We have to remember to look at the nails. Commonly, we don't, but nail disease may be frequently present. We have to remember also with a full history to ask about vaginal symptoms. Dyspareunia, vaginal lichen planus may be present more commonly than we're often aware.

So, patients with LPP may be asymptomatic, but very often they present with symptoms. They present with itching and burning. Their scalp feels tender. Sometimes it feels on fire. And very often, it's the central scalp that's located that is the location of the scarring alopecia. It's important to understand that there's an overlap between the regions of the scalp where female androgenetic alopecia presents and regions of the scalp where lichen planopilaris presents. This photograph shows sort of a top-down, bird's-eye view of the scalp in three women with lichen planopilaris, and what you can see here is that the central scalp is affected. Do these patients probably have androgenetic alopecia as well? They probably do. There's a common overlap between these two conditions. But remember, androgenetic alopecia affects 40% of women. And so, there's going to be a lot of patients that have lichen planopilaris and androgenetic alopecia. Again, the location of the central scalp raises our suspicion, but things like trichoscopy help us to take that from a suspicion to a much greater likelihood that this is lichen planopilaris. That was one example of the perifollicular scale. Here's another example of the perifollicular scale in lichen planopilaris, where we see this whitish scale around hair follicles. It's important to remember that not all patients have scale. If your patients have washed their hair before they come in, if they've been using certain treatments, they may not have scale.

Another patient with lichen planopilaris with not a lot of scale. The thing that's important to remember about lichen planopilaris, which is not pathognomonic of the condition, but is very much a feature of the condition, is what I call the "sea of singles," where we see a large number of single hair follicles. Normally, hairs come out of the scalp in groups of one, two, or three hairs. That's normal. So, we should be seeing follicular openings with one hair coming out, some with two, some with three. When we see a large number of hair follicles with just one hair coming out, we have to recognize this is abnormal, and we have to at least be suspicious about a number of conditions like lichen planopilaris. We do see this as well in some cases of androgenetic alopecia. We could see this in frontal fibrosing alopecia as well. But we have to be aware of this pattern. Another patient with a large number of single-haired follicles. She has itching. She has burning. She has tenderness of the scalp. This is lichen planopilaris.

So, how do we treat lichen planopilaris? Well, the goals of treatment are to help the patient feel better, to reduce their symptoms, to reduce their shedding. But of course, what we want to do is we want to stop their hair loss. And we have to keep both in mind. We want our patient's itching, burning, and pain to stop, but fundamentally, we want their hair loss to stop as well. But we want to ask about all of these things and follow all of these things.

So, how do we treat LPP? Well, I generally believe that in these scarring alopecias, it's important to think about treating them aggressively. Meaning, I would much rather a patient consider treating their scarring alopecia with systemic therapy to stop it, rather than following them with creams and lotions and injections for a long period of time and finding out that they're not helping and then moving on to systemic treatment. By that time, they've lost hair, and it's too late. It's, of course, a clinical judgment, and that factors into this to a great deal. But one needs to always remember that moving on to systemic treatment may be an important consideration.

For localized areas of LPP, where there's a small area that's affected only, certainly steroid injections can be very helpful. Five milligrams per milliliter every six to eight weeks is generally what I do in the clinic. Steroid injections can be extremely helpful for patients with lichen planopilaris. They take time. You need the openings in the clinic to be able to facilitate patients for steroid injections. But for some patients, steroid injections can be extremely valuable. Not for everyone. And there are some patients which will give histories that steroid injections may have even worsened their LPP. It's hard to decipher what's going on in some of these stories. But for many patients, steroid injections can be extremely valuable.

What about topical treatments? Well, topical steroids, especially class one steroids, can be very helpful. And clobetasol propionate is a go-to agent, either as a lotion or as a cream or as a shampoo. I may use fluocinolone oil to help remove scales. It's very soothing. It helps patients deal with the dryness. Some patients will tolerate tacrolimus ointment. Some patients will find this far too greasy. In which case, we'll compound tacrolimus instead of a lotion. And this is a treatment that I learned from Vere Price many years ago. And some pharmacies are good at compounding tacrolimus instead of a lotion. And the consistency of these products varies greatly. And so, it's important to ask your patient what their product looks like. If it's too gunky or gooey or thick, one may need to consider that this may not have been compounded in an ideal manner.

So, with steroid injections, of course, many of you are aware of this. We use a 30-gauge needle, and we inject small amounts, 0.05 mL, 0.1 mL, in these areas around the perimeter of the active area. So, here's a patient with lichen planopilaris, and the injections here would be performed at the perimeter. If there were no side effects with steroid injections, and if one could inject as much as they wanted, one could consider injecting in the center. Could there be some hair follicles that could regrow? It's unlikely, but it's possible. But really, to stop the disease, and because we're limited in the amount of corticosteroids we can use, it's the perimeter that we want to inject to stop the disease in its tracks. As we'll see in a minute, this is very different than discoid lupus, where we inject often in the center of the scalp. If a patient has burning and symptoms in the center of the scalp, that is one consideration where steroid injections in the center could be a good idea.

So, how do we treat more extensive disease? Well, I have a low threshold for moving on to systemic therapy in lichen planopilaris. There's no formal proven option on what a starting systemic treatment will be. There are some colleagues, colleagues in France, colleagues in Europe, that value the role of cyclosporine in treating lichen planopilaris. But generally speaking, doxycycline and hydroxychloroquine are my starting agents for the treatment of lichen planopilaris. And I developed this as sort of my go-to protocol from Dr. Vere Price many years ago, and it seems to be a reasonable approach. And one of the benefits of doxycycline, tetracycline, and the tetracycline families is they're fairly well tolerated for most people, and they don't require bloodwork monitoring. And the side-effect profile tends to be a little bit better than hydroxychloroquine. And so, often, if there's minimal infiltrates on biopsy, or I'm looking for a starting option as empirical therapy, I may start doxycycline 100 milligrams daily, or twice a day. Doxycycline can cause GI upset. It needs to be taken with food. It can cause increased sensitivity to the sun. It could cause headaches. It could cause vaginal yeast infections. It can cause weight gain in some patients. So, one needs to be aware of the side effects and the long-term side effects of doxycycline. You know, many of these systemic agents, when we start them, we think about using them for six to nine months before we determine how well they're working. For doxycycline, I often use them for three, four, five, six months before determining if they're working. But we need to look at what are the implications on the gastrointestinal system if a person's on doxycycline for two years, three years, four years. So, we need to keep this in mind.

If a patient has more inflammation on biopsy, or has failed doxycycline, hydroxychloroquine is often my go-to agent. And it's important to remember the dosing. That hydroxychloroquine, the dosing that is agreed upon now for safety is five milligrams per kilogram. This slide five years ago may have said six milligrams per kilogram, but we've realized that by using the patient's weight, their actual weight, not their ideal weight, if we use a number, five milligrams per kilogram, we have a better safety margin. Hydroxychloroquine requires monitoring of CBC. Hydroxychloroquine requires monitoring of the liver enzymes. And of course, requires a baseline eye exam for the possibility of retinopathy. And we know that the chance of retinopathy is about 1% after five years. It rises to about 2% after about ten years. But after about 20 years, it rises to close to 20%. And so, the risks for retinopathy really increase as time goes on, especially after seven, eight, nine years. But there's a low risk in the early stages. And so, it's important to understand the risks of retinopathy and refer your patients to baseline eye checks within the first six months of even hydroxychloroquine. The guidelines are changing, but often the new guidelines would suggest that in low-risk patients, if they've had a baseline eye exam, that they can then be seen quite a number of years later, not necessarily every six months to a year.

And so, these are the systemic agents that I'll often use. I'll continue steroid injections, and we'll use topical steroids as well. Doxycycline, often used for three to six months to determine if it's working. Hydroxychloroquine, I like to extend a little bit longer before determining if it's working, because it takes longer. They even take six, seven, eight, nine months before I'm absolutely convinced that hydroxychloroquine is working or not. And my personal view is it's important not to give up too early with hydroxychloroquine.

There are other agents. There's mycophenolate mofetil, which studies have shown it can reduce some of the symptoms of lichen planopilaris. Cyclosporine can be used. Methotrexate can be used. Where these fit in a hierarchical category is controversial. There are limited studies which suggest that in some patients, methotrexate is superior to hydroxychloroquine in the treatment of lichen planopilaris. And so, we've still got a long way to go in terms of understanding which of these immunosuppressants is superior. But by understanding the side effects of these agents, you can speak to our patients about how these should be used. Sometimes we use prednisone as a bridge therapy. Pioglitazone, the PPAR-gamma agonist, could sometimes be used. We have to be aware of its side effects. We have to be aware of some of the warnings around the increased risk of bladder cancer. Retinoids are very effective in lichen planus. They're not so effective in lichen planopilaris of the classic sense, but maybe in frontal fibrosing alopecia. And remember finasteride as well. There are a certain number of patients with lichen planopilaris that respond well to finasteride. And so, there may be more of a hormonal basis to a proportion of women presenting with lichen planopilaris than we're often aware. And so, finasteride is definitely on the list as a potential option, especially in postmenopausal women. And Jerry Shapiro had a very nice study recently looking at a small number of patients who responded to low-dose naltrexone. And low-dose naltrexone may also be on the list of potential options. It's a relatively inexpensive treatment with a good side effect profile. And three to four and a half milligrams nightly before a patient goes to bed can provide some patients with benefit.

So, these were studies dating back a number of years ago, in 2010, showing that hydroxychloroquine and mycophenolate can reduce the signs and symptoms of the disease, the so-called lichen planopilaris activity index. But remember, if a patient's responding well, we want to think about, "Do we need to continue this treatment?" For some patients, we do. We need to continue them on this treatment for many years. And so, when patients ask me at early appointments, "How long am I going to need to be on this?" the answer is, "It's not clear for you, but it could be many years." But we try to have them on the lowest dose for the shortest period of time. If a patient is not improving, if they're continuing to lose hair, then clearly we need to change treatment.

And what about hair transplantation? Well, hair transplantation is a very important topic, and one of my favorite topics in the hair transplant field. And that is, when can we transplant, and which scarring alopecias can we transplant? Scarring alopecias can be successfully transplanted, but provided the disease is quiet, and ideally, a patient is off treatment. So, if a patient's disease is quiet for two years, meaning we take a picture today, the patient is off treatment, we take a picture two years later, and we compare these pictures. If the patient's pictures look identical, and they have no symptoms, and they're not on treatment, this patient's condition would be deemed inactive, and they're probably a good candidate for surgery. That does not mean their surgery will be a success, but it means the chances of their surgery being successful are much higher. And certain conditions like lichen planopilaris are often more successful than other conditions like pseudopelade or folliculitis decalvans. And so, there's a lot that we have to learn with the hair restoration field and treating scarring alopecia.

Now, back to this patient who was started on hydroxychloroquine. She has steroid injections. She's asked to return three months later. Is it working? Well, photographs are extremely valuable. And one of the key things that I'd like to leave you with today, one of the take-home points, is to please consider taking photographs if you're going to monitor patients with scarring alopecia. And if you're not able to take pictures, make sure that they take pictures. Photographs are extremely valuable in the management of scarring alopecia.

This patient returns to clinic. Her photographs show that she's doing worse. And so, when I monitor patients with scarring alopecia, I look at the photographs. I look at their symptoms. I look at their signs. I look at the sites of their hair loss. And I look at the trichoscopic signs. These are the so-called four S's. I look at their symptoms. If the patient's itching and burning is getting better, I'm pleased. It just means we're making headway in terms of improving their disease. I ask them about their shedding. Is their shedding reduced? I look at the specific sites. Are these specific sites where the disease is active? Is it expanding? Is there less scale in that area? Is there less redness in that area? And if so, it would indicate that their disease is improving. And so, in this particular patient, in this table, she comes back to see me three months later. Her symptoms are worse. Her shedding has not changed. The scalp sites show that they're still expanding hair loss. It's worse. And when we look at these target areas by trichoscopy, there's no change. So, clearly, she's worse. Photographs are absolutely essential in monitoring scarring alopecia.

This is a patient who has scarring alopecia, comes back to see me six months later, and what we can clearly see is that the area of hair loss is worse. And what is surprising in many of these patients is that they will tell you that they feel their hair loss is the same. And with old photographs, it is extremely difficult to accurately monitor scarring alopecia in these patients. And so, what are the top three pearls with LPP? Well, LPP is probably more common than we realize. We need to be on the lookout for these patients, especially patients who present with burning and tenderness and pain. We need to consider treating these patients for at least three, four, five, six months before we're confident that our systemic agent is working. Some agents like cyclosporine work quickly. Agents like doxycycline work relatively quickly. Hydroxychloroquine may be a little bit more, maybe slower in its onset of action. And you can't tell lichen planopilaris is active or quiet easily based on the first visit. You certainly can't tell LPP is quiet based on the first visit. If your patient does not have any symptoms, and you look at the scalp and it appears quiet, your tendency is to feel that their disease is quiet. If you look at a photograph six months later, and they've lost hair, then their lichen planopilaris is active. And so, the tendency is to look at the patient at visit one and say, "Your LPP is quiet. You're ready for surgery." Or, "Your LPP is quiet. You don't need any other treatment." You cannot tell lichen planopilaris is quiet at a first visit. Now, often, of course, you can tell LPP is active at a first visit, but there are exceptions. There are some patients with persistent redness in the scalp from long-term corticosteroid use or steroid injections that doesn't necessarily mean that their LPP is active. But a photograph six months later, or a year later, or two years later, will be the ultimate judge if their LPP is active. And I prefer photographs over repeat biopsy. Repeat biopsies, of course, an option, but there are many patients with quiet LPP where they have no hair loss over an extended period of time, but a repeat biopsy will show a few lymphocytes in that biopsy.

It's a patient with the next scarring alopecia, which is frontal fibrosing alopecia. This is the second lymphocyte-associated scarring alopecia that we're going to talk about. This patient presents with hair loss along her frontal hairline. And this is thought to be a variant of lichen planopilaris. FFA is increasing. We don't know why, but many of

You in the room today are probably seeing a lot more patients with FFA. It was first introduced in the literature in 1994 by Dr. Koh Surd. It's a disease of postmenopausal women, but of course, younger women are affected as well. And you can see FFA in women in their 30s and in their 40s, but the majority of patients are postmenopausal women.

The eyebrows are lost in many of these women, and they may be a first sight of disease in many women as well. And one of the points I'd like you to remember is that any 50-year-old woman, or 60-year-old woman, or 70-year-old woman who presents to you with eyebrow loss, significant eyebrow loss, frontal fibrosing alopecia, needs to be at the top of your list. This is how women with FFA present. It's a much more common for these women to have FFA than alopecia areata.

If you inject these eyebrows thinking that, "Let's see if they grow hair back when I inject them," remember, some women with FFA will grow back eyebrow hair with steroid injections. It's called frontal fibrosing alopecia. But women lose hair on the arms. They may lose hair at the ocular scalp, and we're learning more and more about this condition over time, and it's a very interesting condition.

There's clearly a hormonal base to FFA, and some studies have suggested an association between early menopause. The reason I want you to be aware of this is that if you see a patient with FFA and she's 38, 41, 32, and she's interested in having a family and has not yet had a family, one needs to keep the concept in mind that FFA is associated with early menopause, and one may consider a number of tests to evaluate further for the menopausal status of that young woman affected by FFA.

When we look at the scalp of patients with FFA, you look for this border between the sun-damaged skin and the very smooth, scarred scalp of FFA. And these arrows here show that delineation. There may be atrophy, so you may see the scalp veins much more clearly in women with FFA, and it's very important to be aware of that atrophy. And it's very important to take photographs at the first visit. That atrophy, many women with FFA present with visible veins and atrophy.

Over time, the use of topical steroids may lead some patients to believe that the topical steroids or steroid injections led to worsening atrophy. In the vast, vast majority of cases, my belief is that the atrophy is coming from the FFA, and the aggressive treatment with corticosteroids in most cases actually helps stop the disease, or at least helps the disease rather than further contributes to worsening atrophy. Of course, there are exceptions, and steroids can worsen atrophy, but having photographic documentation at the first visit is very valuable.

The thing to remember is that the hairline is affected in frontal fibrosing alopecia in many patients, not all. It may be just eyebrows that are lost. It may be sudden loss of body hair that is their clinical presentation initially, but you want to look at the frontal hairline. And you can see in these photographs on the left, these two women with androgenetic alopecia have preservation of their frontal hairline. The very frontal hairline contains hairs. These two women on the right side have loss of their frontal hairline. It's moved back. They have regression of this area. There's no hair in this area. And of course, you look for this border when you look up close at the scalp of patients with FFA.

It's important to know what you're looking for. You're looking for evidence of hair loss. You're looking for redness around the hairs. You're looking for hairs, what we call lonely hairs, meaning isolated hairs quite a distance in front of the existing hairline. You may see highly torti, meaning some of the hairs are twisted. That's a very common finding in many patients with FFA. And you may see these visible veins.

Here's another picture up close showing the visible redness around the hair follicles, a so-called perifollicular redness. In this particular photograph, we don't see that much visible vein, so there's not a significant degree of atrophy. There may be a small amount, but we see the redness and we see some of these lonely hairs. We see some of these hair follicles just sitting out quite a distance away from the main hairline.

And Dr. Tosti in 2011 in the Archives reported the so-called lonely hairs of frontal fibrosing alopecia. And of course, there were a number of rebuttal letters saying that lonely hairs are not pathognomonic of frontal fibrosing alopecia. They're seen in many hair loss conditions, and of course, that's true. The comments in the original article was never that lonely hairs are pathognomonic about FFA, but that they're a feature of FFA that we should all be looking for.

The condition is called frontal fibrosing alopecia, but remember that the hair loss can go around the sides and to the back of the scalp. It could affect the eyebrows, the eyelashes. It can affect body hair. And so the term "frontal" is only part of the scalp involvement. The back of the scalp is commonly involved in women with FFA, and we need to look especially in these corners just behind the ears. That's a common area where FFA presents well ahead of any involvement of the main mid-scalp, or mid-mid-back occipital area. Some patients have a bit of edging in that area.

And when you look up close, you may see definite areas of scarring, like we see here. When we look at the scalp by trichoscopy, we look for the redness around the hair follicles, the perifollicular redness. And FFA is very important because it may indicate activity. Patients with FFA who have perifollicular redness are more likely to go on to lose hair than patients that don't have that perifollicular erythema.

We need to look for these visible veins. These visible veins, as I mentioned, are from atrophy, and we need to follow it. The other thing that's become increasingly apparent in the last few years is the so-called facial papules. As humans, we have countless number of hair follicles on our face, and it's come to be understood that these tiny hair follicles can be the target of inflammation in FFA. And when inflammatory infiltrates attack hair follicles on the face, the result is facial papules. And many patients present with these flesh-colored bumps along the face, along the temples, that they may not be aware are related to their FFA. But when you look up close, you could appreciate that they're there.

And Dr. Dina D'Alene did some very, very nice work early on looking at the origin of these facial papules and coming to understand that any of them involve inflammation within vellus hairs of the face. But the other thing that I want to mention is sideburn loss, because any patient that presents with symmetrical sideburn loss, one should have a high index of suspicion for FFA. This is especially true in men that present with symmetrical sideburn loss, but it's also present in women. And so the sideburns are important to examine. And very rarely, this is the first area where the hair is lost. Of course, if the sideburn is lost here and no other area is lost, one needs to consider other entities. But symmetrical sideburn loss, one needs to have a high index of suspicion for frontal fibrosing alopecia.

So, what causes FFA? We don't know, but there's thought to be an environmental factor that's contributing to the development of FFA. When you think about FFA, it wasn't reported in the dermatological literature until 1994. But after 1994, cases started to appear with Dr. Car's first report. This was a study looking at the possibility that sunscreens contribute to some patients with FFA. This was a study from the UK by Dr. Messenger's group. It got a lot of attention. They gave questionnaires to patients with FFA. They gave questionnaires to patients without FFA. And these questionnaires ask a lot of questions, including how often do you use sunscreens. And what this study showed is that a greater proportion of women with FFA reported using sunscreens more than twice a week compared to women without FFA.

Of course, there are limitations to any study. There are limitations to questionnaire studies. There are limitations to retrospective studies. But this was one of the first studies which tried to look at some environmental factors which could be involved in FFA. This study questionnaire was replicated in with FFA by Dr. Messenger's group as well. And that particular study showed that men with FFA reported a higher proportion of men were using sunscreens than men without FFA. Again, a second study, at least pointing to a potential relationship with sunscreens.

There's a lot of controversy around this study. There's a lot of naysayers and who have targeted this study. But the study is valuable because it points to a way of thinking about some of these environmental factors. There's thought to be an environmental factor that's responsible for FFA in a large proportion of patients. Some patients clearly have a genetic background as well, because you can get FFA in sisters and relatives and and parents, mother and daughter. But the search is on for an environmental factor which could be contributing to this disease.

How do we treat FFA? Well, largely, we treat FFA the same way we treat lichen planopilaris with some exceptions. And it's the exceptions that are important to understand. FFA is a lymphocytic-associated scarring alopecia. So anything that chases away a lymphocyte is probably going to do something for FFA. How well it works is a different story. And so treatments like hydroxychloroquine, doxycycline, topical steroids, steroid injections, methotrexate are probably going to help frontal fibrosing alopecia, and there's evidence that they do.

However, two treatments are quickly rising to the top of the list as perhaps the most valuable treatments in FFA, and that is the 5-alpha reductase inhibitors, dutasteride and finasteride, and the retinoids. It's still controversial in how well each of these work, but there's been some very good studies, especially studies from Spain, looking at the role of dutasteride and finasteride in large numbers of women with FFA, showing that these can stop the disease in a significant proportion of women and actually regrow hair in a significant number of women as well. And today, these 5-alpha reductase inhibitors are the only treatment that has the potential to regrow hair in FFA. Of course, it doesn't regrow hair in all women with FFA, but there's no evidence that we can get significant hair regrowth with hydroxychloroquine, doxycycline, steroid injections, calcineurin inhibitors. So it's exciting.

And studies from Poland have now suggested that perhaps retinoids are at the top of the list as well for our management of frontal fibrosing alopecia. And if, as I mentioned before, we started the lecture, copies of these references have been handed out as well. So here's a patient with frontal fibrosing alopecia who has been started on oral finasteride at 2.5 milligrams, and what we can see here is regrowth. There's a reduction in atrophy. There's a reduction in visible veins, and there's a regrowth. Now, we don't see this in all patients, but this is something that we're seeing increasingly and not all that uncommon. And so the 5-alpha reductase inhibitors certainly are exciting, presenting patients with an option for managing FFA.

Do we still use steroid injections, topical steroids, calcineurin inhibitors? Yes. In postmenopausal women, the option of using 5-alpha reductase inhibitors is much easier. In premenopausal women, the 5-alpha reductase inhibitors, of course, one needs to be aware of concerns surrounding pregnancy. These drugs are category X. They're not approved by the FDA or Health Canada or most regulatory agencies for use in women. They are off-label uses. And so we need to explain this to patients. We need to explain this to pharmacists. I frequently get calls from pharmacists about the prescription of 5-alpha reductase inhibitors. The reality is that when prescribed appropriately to the right patient with the appropriate counseling, that these are appropriate off-label uses of these 5-alpha reductase inhibitors for many women, but of course, not all women.

Steroid injections remain an important treatment option for the eyebrows. This is a study that I did with Dr. Price in 2010 looking at steroid injections in FFA. And one of the surprises of this study, which was published in the BJD, was that many women with FFA improve their eyebrow density with steroid injections. And the key take-home message of using steroid injections in FFA is that when you inject the eyebrows, if you see hair growth three months later, it's appropriate to continue. If you don't see eyebrow hair growth three months later, it is unlikely that steroid injections are going to help. And so I do not repeat steroid injections again if I'm not seeing hair regrowth. And remember, photographs are essential, just like in lichen planopilaris. Photographs are essential. Photographs are absolutely essential in FFA.

FFA is much more asymptomatic than lichen planopilaris. There are patients who come back to clinic, they say that everything is going well, they're very happy on the current treatment. When you compare their photographs side to side, what you see is they have significant hair loss over the interval period of monitoring. Treatment of FFA is challenging. 5-alpha reductase inhibitors, as well as retinoids, are probably at the top of the list. Hydroxychloroquine can be used. Doxycycline can be used. Topical steroids and steroid injections can be used. Take photographs. These photographs will be extremely valuable for understanding the disease activity in the patient.

Next patient is a 34-year-old female with afro-textured hair who's losing hair slowly. She has no symptoms. Many of these patients come in to see us with a previous diagnosis of androgenetic alopecia, which some of them may have. But the key point I'd like you to recognize immediately in this patient is that all black women with central hair loss who are between 33 and 49 have CCCA until proven otherwise. You may be proven wrong, but I assure you, you'll be proven right much greater proportions of the time.

CCCA can be symptomatic. These patients can present with itching, burning, tingling, but they can be asymptomatic, especially when you see them. They may be symptomatic with tingling when their disease first develops, but they're often asymptomatic by the time they see you. When you look up close, they may have scale, and you may be apt to say that this is seborrheic or tinea. Many of these women don't shampoo their hair often. But one of the trichoscopic findings of CCCA, which is challenging sometimes to identify, is this so-called perifollicular gray halo. There's a little bit of this discoloration around the hair follicles. This is CCCA.

Central centrifugal cicatricial alopecia is challenging, but what's not challenging is realizing that any black woman with central hair loss who's between 33 and 49 could have CCCA until proven otherwise. That's what makes diagnosing these conditions much easier. These patients often start with hair loss on the central scalp, but it spreads out over time in a centrifugal fashion. That's where that name comes from. So it starts centrally, spreads centrifugally, it causes scarring that's cicatricial, and it causes hair loss that's alopecia. That's how we get central centrifugal cicatricial alopecia.

We don't know what causes CCCA. It's one of the most common causes of scarring alopecia in black women, and it's much, much, much more common than we realize. And so if you have an index of suspicion for CCCA, you're going to identify it a lot more often. It begins in middle age. There are reports of CCCA in very young children. These studies are challenging not to say that there's not CCCA in younger individuals, but one needs to look carefully at the study design of some of these studies. But CCCA often presents a little bit older. It can be challenging sometimes to differentiate from traction alopecia. It can be challenging to solely identify CCCA based on histopathology, which is a topic for another lecture. But certainly, there are pathognomonic features with histopathology of CCCA, and one can identify CCCA based on biopsy. But one has to keep in mind in some of these studies that one of the studies which needs to be done is the evaluation of scalp biopsies in asymptomatic women with afro-textured hair who do not report hair loss. What you'll actually see in these studies is that many women have features of CCCA. These are asymptomatic women with who are not reporting features of hair loss, who are between 35 and 70. And so we have a long way to go in terms of understanding CCCA, what is its presentation, what is its true histopathologic features, and what causes women with CCCA histopathologically to develop hair loss.

But CCCA often is asymptomatic. Patients may present with itching, burning, tingling, but most often it's just pins and needles or no symptoms at all. But many of these women report hair breakage in the earliest stages. These were studies by Dr. Sperling and colleagues where women who presented with hair breakage underwent scalp biopsy. And what these studies showed is that many of these women, this was a small study of nine patients, but many of these women were diagnosed with CCCA. So we have to be aware of our patients who present with hair breakage that this may be one of the earliest, earliest signs of CCCA.

When you look up close on the scalp, it may be smooth, shiny surface. You may not see inflammation, and you may see islands of hair and areas of no hair and islands of hair. Remember, when you look up close on the scalp, you may not see inflammation. And so the tendency in evaluating a patient with CCCA is to look at the scalp and to say, "It looks non-inflammatory to me. I don't think it's active. I don't think you need treatment." This is where we often go wrong because many of these patients come back to you six months later and they say, "I'm losing more hair." Clearly, their condition is active. The lack of inflammation on clinical exam does not mean their condition is inactive.

Many of these scarring alopecias are thought to proceed along their course if untreated and eventually burn out. We do not know in the present day that all scarring alopecia burns out, but certainly a number of scarring alopecias may burn out over time and become inactive. And in the end, these scarring alopecias in their end-stage, burnt-out stage, look very similar to all scarring alopecia. There's scar tissue, there's lots of sebaceous glands, and there's loss of hair follicles.

What causes CCCA? We don't know. Is it genetic? Is it metabolic? Is it due to follicular trauma? The best guess is that there's probably some susceptibility that causes these women to develop a scarring inflammatory response to some sort of scalp trauma. And whether this trauma is hair styling practices, we don't know. That's controversial. But we know that there is probably this genetic susceptibility. CCCA is one of the scarring alopecias where, at least in some women based on studies in South Africa, there's a genetic basis. We do not have that same confidence about a genetic basis for scarring alopecia for many of the other scarring alopecias. But CCCA may be one of the first scarring alopecias.

And what we have come to understand is that in studies in JAMA Dermatology recently, is that there's an increased risk of uterine fibroids, in fact, a fivefold risk in women with CCCA. So there may be this inherent tendency to develop a scarring response in certain tissues in the body.

Do hair care practices cause CCCA? Well, it's a great subject of debate. Do relaxers cause hair loss? What about braids, weaves, cornrows? We don't know. Some studies have suggested yes, some studies have suggested no. But interestingly, some studies have suggested that wearing the hair natural before the age of 20 makes it much more unlikely to develop CCCA later in life. And so there may be this trauma, chronic trauma to hair follicles that develops that then leads to this CCCA-like inflammatory response.

How do we treat CCCA? A lot of that is based on clinical judgment. It's clear that reducing inflammation is valuable. And so we use anti-inflammatories that chase away lymphocytes, just like we do in the other lymphocytic scarring alopecias. It's not, we're not confident that reducing hair care practices has a huge impact on CCCA, but certainly there may be some discussion whether reducing heat or relaxers or traction could have some benefit. And for some women, wearing hair natural for periods of time may be beneficial. Clearly not for all women. This may, may not be practical for all women. If women are relaxing their hair, certainly relaxing, spacing out the relaxing as far as possible may be valuable. And certainly, if there's going to be trauma to the scalp, whether heat or chemical or coloring, that these should be spaced out as far as possible to limit trauma to the scalp.

The treatment of CCCA is not agreed upon. But certainly, my approach is generally using a topical corticosteroid with steroid injections periodically with the use of a systemic anti-inflammatory agent like doxycycline. We have to think about the possibility of pigment changes with the use of corticosteroid injections. So I typically use 2.5 to 5 milligrams, injecting every four to six weeks, and monitoring these changes in pigmentation. Corticosteroid injections in CCCA can be very, very helpful for many women. And I am of the belief that the use of a systemic anti-inflammatory agent like doxycycline, if tolerated, can be very helpful for many of these women, especially for a period of three to six months. We often use fluocinolone oil. Many women with afro-textured hair use various oils on the scalp, and fluocinolone oil is very well tolerated. Minoxidil can be used. I think we're coming to understand, especially from some of the great work at the Cleveland Clinic, is that there may be more overlap between CCCA and genetic hair loss than we appreciate. But certainly, minoxidil can be used in these patients and may be beneficial to many of these patients. But we have to think about vitamin D deficiency. We have to think about iron deficiency. We have to think about other deficiencies and treat them. Many women with CCCA are vitamin D deficient. A proportion are iron deficient, and we need to correct these deficiencies as well.

We don't know appropriate second-line systemic agents. In fact, hydroxychloroquine, CellCept, which is mycophenolate mofetil, which is commonly used in LPP, is largely ineffective in many patients in our clinic with CCCA. If the disease is quiet, hair restoration surgery, hair transplants can be very helpful for CCCA, but the condition has to be quiet, which again is no change in hair loss over a period of one or ideally two years, no ongoing symptoms, and ideally off treatment. Early treatment of CCCA can lead to regrowth, especially with what I would consider more aggressive treatment, which would be steroid injections every so often, four to six weeks, corticosteroids used topically, and the use of an oral systemic agent like doxycycline. Remember the power of recognizing the anatomic location that CCCA presents centrally. And so black women presenting with central hair loss, one should be on, on have their radar out for the possibility that this is, in fact, CCCA.

Let's talk about some other scarring alopecias, just briefly. This is a patient who presents with hyperpigmentation, hypopigmentation, and hair loss. This is discoid lupus. Discoid lupus is one of the scarring alopecias which presents with these pigmentation changes, and it's important to recognize because a proportion of these patients may develop systemic lupus, and they may develop discoid lesions elsewhere on the body, such as the face, which can be scarring and can be disfiguring.

In early discoid lupus, it can look very similar to lichen planopilaris. You can see this perifollicular scale. You see this whitish scale. Sometimes you can appreciate this follicular plugging as well. You can see these dilated blood vessels, sometimes telangiectasias, and this pigmentation change. But it can look strikingly similar to lichen planopilaris. Late lesions, which we of course want to identify ideally before it gets to a late lesion, presents with this more classic hyperpigmentation, these white, structureless areas, these telangiectasias, and this follicular plugging that is more classic of discoid lupus. So anytime you see this pigmentation change in the scalp with scale, especially if there's telangiectasias, sort of dyschromia, we have to be thinking about discoid lupus.

And the thing I want to mention before moving on is this entity of discoid lupus presenting as frontal fibrosing alopecia. There are some patients that present with classic FFA whose biopsies show features of discoid lupus. And so one needs to be aware of this variant. And so if you have a patient with FFA and you perform a biopsy and the pathologist reads discoid lupus, we need to be aware that this may not be an error. So far in the literature, these patients with the discoid lupus presenting with FFA don't appear to be having systemic lupus. We of course need to be aware of this possibility, but this appears to be a very unique clinical presentation of FFA.

Discoid lupus presents with hair loss in the center of the plaque. And so when you inject corticosteroids into discoid lupus, it's important to inject into the middle of the area of hair loss. In lichen planopilaris, we inject on the outside of the area of hair loss. Discoid lupus and dissecting cellulitis are the two scarring alopecias which, if treated early and aggressively, they have the potential to regrow. We're now considering whether FFA is added to that list. But certainly, in many cases of discoid lupus, our regrowth is able to some degree with the early and aggressive treatment. And so one can consider topical steroids, topical calcineurin inhibitors, the use of retinoids, and one should consider the use of sunscreens in this group. Steroid injections can be very helpful in discoid lupus of the scalp, and one should consider systemic agents such as hydroxychloroquine, which can be one of the number one agents to consider as systemic agents along with methotrexate in the management of discoid lupus. Of course, any anti-lymphocytic agent potentially helps discoid lupus. And early regrowth is possible.

So remember when you see patients with discoid lupus that you want to screen for lupus and you want to follow for lupus. If their ANA is negative, you may, I always tell my patients that they need to be aware of this possibility. So five or ten years down the road, if they're living across the world in another country, another city, we have to be aware that if they present with unusual symptoms, sudden onset of hypertension, joint pain, headaches, that we have to have these patients cued that they say to their doctors, "I was told that my scalp symptoms may be indicative." We need to be on the lookout for systemic lupus at any point in our life. It's not common, but I plant that seed in the minds of our patients because they may not be following up with us forever.

Here's a patient who presents with central hair loss. It occurs midline. And this is a patient who, when we look up close, the scalp doesn't look very red. There's no scale around the hair follicles. We see some of the hairs around the perimeter of these scarred areas undergoing twisting. That's what we call pityriasis. When you look in the center of those areas of hair loss, you don't see the follicular ostia. Again, as proof this is a scarring alopecia. This is pseudopelade.

Pseudopelade is a scarring alopecia which can present with burning or itching. You don't generally have the same amount of scale and redness that you have in lichen planopilaris. It can often mimic alopecia areata. And in fact, pseudopelade, of course, means like alopecia. Palade being the French word for alopecia. And so it's not uncommon for some patients with pseudopelade to be misdiagnosed as alopecia areata. It can present with these tiny pinpoint-like areas of hair loss. When you inject these, of course, they don't grow as you would expect them in alopecia areata.

One of the key features of pseudopelade of Brocq is this atrophy. And so when you run your hand, your fingers on the scalp in these areas of hair loss, you see atrophy. You see these so-called footprints in the snow, where your finger dips down in these regions of hair loss. Pseudopelade can affect many areas of the scalp, but it often affects the central scalp. This patient on the left has androgenetic alopecia with a widened part width. The woman on the right has pseudopelade, and what you can appreciate here, even from this view, is these so-called footprints in the snow, this atrophy, these areas of hair loss that are extending out from the central scalp.

This is a patient with scarring alopecia whose hair loss hasn't been active for many years. She had LPP, lichen planopilaris, diagnosed at one point. Now it's quiet. Now it's burnt out. In North America, we would use the term pseudopelade, not pseudopelade of Brocq, but the generic term pseudopelade to describe any burnt-out scarring alopecia. The use of this term differs around the world how you use the term pseudopelade. But it's a different term than pseudopelade of Brocq. Pseudopelade of Brocq refers to the condition I explained previously with this scarring alopecia presenting with burning, presenting with scarring alopecia and atrophy, and the so-called footprints in the snow. When you use the term pseudopelade, we're referring to a burnt-out scarring alopecia of any ideology. In order not to confuse these terms, my recommendation is to avoid using the term pseudopelade. This patient is better described as a patient with lichen planopilaris who now has end-stage, burnt-out disease, and her condition is not active. But when you have a patient with pseudopelade, we follow the patient the same way we follow their symptoms, we follow their signs, we follow how they're shedding, and we use a camera to follow their hair loss.

Now let's talk about the neutrophilic scarring alopecias for a few minutes, and we'll begin with folliculitis decalvans and then we'll talk about dissecting cellulitis. Folliculitis decalvans is a scarring alopecia that is thought to have some role of bacteria. It's often Staphylococcus aureus that contributes to this condition, but it doesn't have to be. There could be many bacteria that somehow cause the immune system to be on alert. And it's frequently Staphylococcus aureus. And it's not the entire immune system, it's the local scalp immune system that is on alert to destroy bacteria. And why this is, isn't clear, but it's thought that there could perhaps be some sort of biofilm or some sort of a glue that sticks bacteria in the scalp differently in patients with folliculitis decalvans than patients without folliculitis decalvans.

Patients with folliculitis decalvans can be male, can be female. The classic patient is a male who presents with pimples, presents with itching and burning, especially in the crown. Initially, there's bumps, there's pustules, there's a folliculitis, and then these bumps break down. Instead of these bumps healing like they do in a folliculitis, they don't go away, they leave a scar. And some of these bumps have pus that come out of them, and then these bumps expand over time in the areas of hair loss, expand over time.

Folliculitis decalvans can affect the mid-scalp, it can affect the frontal scalp. But this area of so-called fronto-crown folliculitis decalvans is a very common clinical presentation for you to recognize. And so any male patient who presents with burning of the crown, with pustules, of redness, of bumps, should be thought to have folliculitis decalvans, especially if there's evidence of scarring. There are some cases of lichen planopilaris which can mimic folliculitis decalvans that are challenging to tell apart. But again, the crown is a very common area for folliculitis decalvans. And one of the helpful questions for delineating or differentiating folliculitis from folliculitis decalvans is, "Do you wake up with blood on your pillow?" Patients with folliculitis decalvans often will say, not always, but they'll often say, "Yes, in fact, I do wake up with blood on my pillow."

When you look up close with trichoscopy, it's easy to understand why they get this bleeding. Here's a classical image of folliculitis decalvans with redness and scarring. There are these dilated blood vessels in areas. This particular patient has tufting, or the presence of compound hair follicles, where in this case, there's 12, 13, 14 hair follicles that are fused together from a single follicular ostium. That's very typical. And so this tufting is very common in folliculitis decalvans. It doesn't have to be, but this so-called tufting is frequently present. There's often purulent material. So when you push on some of these bumps or papules, there's pus that comes out. And tufting, or this grouping of follicles, it's very common in neutrophilic dermal scarring alopecia.

So normally, there's one hair that comes out of a pore, or two hairs, or three hairs. That's normal on the scalp. When you look at the normal scalp in lichen planopilaris, the most common thing to see is one hair coming out of a single pore. But on conditions where you see more than six coming out, this is what we call a compound hair follicle. And compound hair follicles are very common in these neutrophilic scarring alopecias. This neutrophilic inflammatory response creates almost like a neutrophilic soup that causes these hair follicles to fuse together. The photograph on the upper left is folliculitis decalvans. The bottom right is lichen planopilaris.

How do we work up folliculitis decalvans? Well, we culture anything we can find. We culture these pustules, we culture scale, we even take hairs and we put them in a culture container. We try to identify what bacteria is on the scalp, what bacteria is in these pustules. It's often Staphylococcus aureus, but it doesn't need to be. And the lab will tell us what bacteria is present and what antibiotic will work. I recommend culturing the nose to determine if they're a Staphylococcus aureus carrier and to perform a skin biopsy.

How do we treat folliculitis decalvans? Well, we treat according to what the lab tells us the culture and sensitivity is. So if they identify a particular bacteria and they tell me it's only sensitive to Septra, trimethoprim-sulfamethoxazole, that's the agent that I will certainly consider using. But frequently, it's Staphylococcus aureus, and frequently it's sensitive to some agent. And if I can't find a bacteria, which sometimes happens, then we need to think about what empiric therapy will we start. Certainly, topical steroids can be helpful in some patients to reduce inflammation. But an antibiotic like topical mupirocin can be helpful. Topical clindamycin can be helpful. Oral doxycycline can be very helpful in folliculitis decalvans. Sometimes we will consider clindamycin with rifampin. And there's a lot of evidence to support these two antibiotics at 300 milligrams twice a day for ten weeks, and then repeating it again, 300 milligrams twice a day for ten weeks. And if the disease is still present, completing a third cycle. Early studies have suggested that clindamycin or rifampin can help many patients with folliculitis decalvans. Of course, the prolonged use of clindamycin does increase the risk of GI side effects and serious diarrhea. And so we need to be aware of that and consider that in our choice of therapy. Rifampin is a wonderful antistaphylococcal antibiotic. It gets into these areas quite readily and has a wonderful treatment. We never use rifampin alone because of resistance, but rifampin can be used with clindamycin. It can be used with ciprofloxacin. It can be used with cefalexin, doxycycline.

What is the ideal treatment for folliculitis decalvans? We don't know. Certainly, antibiotics are helpful. Doxycycline is helpful. Clindamycin-rifampin is helpful. But there's some debate in the literature in terms of what's the most helpful treatment. Is it antibiotics or is it isotretinoin? And so there's an abundant literature appearing over the last few years which has suggested that isotretinoin is also a very important agent to consider in managing folliculitis decalvans, and it may reduce the flares that patients have. And so I may consider antibiotics in patients if their treatment is very responsive to antibiotics and their disease stops and they don't need ongoing courses, then that's great. But in patients that are refractory to multiple antibiotic courses, I certainly consider isotretinoin. That's an important option.

If we grow Staphylococcus aureus in the nose, then we treat with a mupirocin protocol where we treat a week of the month, the first week of the month, for several months in a row, especially three months in a row. We may consider cleansers as well on the scalp. I'm certainly moving in favor with triclosan as the days go on, but there may be other antibacterial agents that we can use. And certainly, the days of using many of these antibacterial agents like Fucidin X R are falling out of favor, but there may be some antibacterial agents that we can continue to use which are deemed much safer. Triclosan, as you know, is becoming banned in some countries. We still do have it in Canada, and it still is an option for our patients. But antibiotics are very helpful.

This patient was started on six weeks of cefalexin. His folliculitis decalvans cleared. And in this particular patient, his folliculitis decalvans remained at a quiet state with the periodic use of a corticosteroid, corticosteroid injections, and periodic topical antibiotics.

So finally, we'll talk about this patient. A patient who presents with discharge of these areas of the scalp. It's purulent, serosanguinous discharge, where he pushes on one area of the scalp and pus comes out of another area of the scalp. There's an odor to these discharging areas. And so as soon as you walk in the room, it's clear what this patient may have. This is dissecting cellulitis.

A challenging condition. It's a condition that commonly presents in black men aged 20 to 40. The thing that's important to remember in this particular epidemiological statistic is these are young patients. These are patients at the start of their career. These are patients early on in their social lives. And these can be very debilitating conditions. They present with boggy sinus tracts where they interconnect under the skin. So you press on one area of the scalp and you have pus coming out of another area. It's not difficult to identify advanced dissecting cellulitis. Patients often come in knowing themselves that they have dissecting cellulitis. What's challenging is identifying the very earliest stages of dissecting cellulitis.

When you look up close to a more well-developed case of dissecting cellulitis, you can see these sinus tracts. You can see these openings in the scalp where pus drains from. They have these painful nodules. And some of these nodules need to be opened and drained to relieve pain. And by incising and draining these nodules and sometimes packing them, it can provide immediate relief to these patients.

The trichoscopy of early dissecting cellulitis is interesting because it sometimes mimics alopecia areata. You have these vellus hairs growing in the areas. You have these yellow dots. But more often than not, you see these sinus tracts present in the skin. But you often see these vellus hairs as well. It would almost make you think that these are miniaturizing hairs, but these are commonly present. When you look up close without trichoscopy, you see these scarred areas and you see these sinus tracts.

What causes dissecting cellulitis? Well, it's thought to be an abnormality of keratinization of the hair follicle wall. The same fundamental abnormality that's thought to be responsible for hidradenitis. Of course, there are differences, but it's thought that there's some abnormality to the hair follicle wall that causes it to collapse. And as a result of collapsing, you get the secondary infection. Many patients with dissecting cellulitis have the so-called follicular occlusion tetrad. And so many patients present with hidradenitis, acne conglobata, pilonidal cysts. And we need to ask. We need to ask our patients with dissecting cellulitis, "Do you have drainage under the armpit, in the groin? Do you have drainage in the buttocks area? Do you have pilonidal cysts?" A large proportion of patients will tell you yes. They may not realize they're connected. Then they may not tell you this spontaneously. So we need to ask.

Despite all of this pus and despite all this drainage, many of these patients, when you swab these areas, they come back sterile. They do not grow bacteria, which is often surprising. The drainage is often sterile. The infections, if there is a true infection, is a secondary infection because the primary abnormality is thought to be a problem with keratinization. The primary treatment are agents such as isotretinoin, which help improve keratinization of the hair follicle wall. And so low-dose isotretinoin is often a first-line agent. And we start low rather than high to prevent flares. It's important to culture any material. And if you do have bacteria come back, it's important to treat these secondary infections. And so some patients with folliculitis decalvans that are not responding to isotretinoin, one needs to think about secondary infection and consider treating either bacteria that are present or treating empirically with antibiotics. And cefalexin may be an option. Doxycycline may be an option. I remind you, of course, that we don't use doxycycline with isotretinoin.

Incision and drainage is helpful. As I mentioned, it's extremely helpful to these patients to open up these areas. Steroids can be used. It's sometimes difficult to inject steroids into these areas, but corticosteroids at high doses, 10, 15, 20 milligrams, can be helpful. And TNF inhibitors are increasingly helpful. A number of them have been studied, and certainly, we've used adalimumab many times in patients with dissecting cellulitis, providing relief to many patients. There are many off-label treatments that have been studied: zinc, dapsone, finasteride, all of the treatments for hidradenitis. Laser to remove the hair follicles have been studied. And even excising the scalp and grafting skin has also been reported in the medical literature as a rather drastic step, but still helpful for many patients. But the early diagnosis of folliculitis decalvans and the early treatment can lead to regrowth in some patients. And again, discoid lupus, dissecting cellulitis, may be FFA. These are the scarring alopecias that have the potential to regrow.

I won't talk much about the mixed scarring alopecias, but I do want you to remember erosive pustular dermatosis of the scalp. This is a mixed scarring alopecia that when you first look at it, it can look frightening. These patients have crust, they have drainage, they may be weeping in the drainage that they have. But they respond incredibly fast to topical cortisone, topical tacrolimus, and in fact, this is diagnostic of the condition. We don't know what causes erosive pustular dermatosis of the scalp, but it's thought that many of these patients have some sort of scalp trauma. Many of these patients have chronic actinic keratoses that are repeatedly treated with liquid nitrogen or 5-fluorouracil or other treatments, and they develop erosive pustular dermatosis. So there's clearly a role for scalp trauma in these patients. They tend to be a little bit older.

The other mixed scarring alopecia is acne keloidalis. This is a very frustrating condition where these patients initially present with these papules on the occipital region of the scalp. These can then expand and coalesce into these large plaques, which you saw in the previous slide. Acne keloidalis is neither acneiform nor showing keloids under histology, but we treat it very similarly to acne with topical acne treatments, retinoids, oral tetracycline, doxycycline, tetracycline family members. And it's clear that excision of these sometimes can be helpful as well, allowing them to heal with secondary intention. And so there's a number of medical and surgical options for managing acne keloidalis, and there's also some laser options as well. A number of lasers have been reported to be helpful, including more recently the 755-nanometer alexandrite.

And so finally, this comes to our conclusion about scarring alopecia. This is a very important subject. We won't go into details about camouflaging options, but I do want to remind you that patients find it helpful when you address these topics with them. They may be frightened to ask. They may be thinking that by asking and broaching these subjects with you, that it's admitting to some sort of defeat in some area that you may not want to treat their scarring alopecia as aggressively. But patients find it very helpful. There are a number of hair camouflaging fibers, keratin fibers, that can be extremely helpful for limited scarring alopecia to camouflage hair loss. This is more helpful in early lichen planopilaris, early discoid lupus, early lymphocytic scarring alopecias. Of course, those kind of camouflaging options are less helpful in frontal fibrosing alopecia.

But everyone here should be aware of the Cicatricial Alopecia Research Foundation, or CARF. Their website is here: carfintl.org. This is a nonprofit organization that funds research in scarring alopecia and has patient-doctor conferences every few years, which are really wonderful weekend conferences where patients and physicians get together to discuss scarring alopecia, to discuss research in scarring alopecia, and just to discuss how scarring alopecia affects patients. And so I would encourage you to connect your patients to CARF. It's a wonderful organization.

What are the take-home messages? Well, there's a number of them, but scarring alopecias are conditions which destroy hair follicle stem cells. And because these stem cells are destroyed, it impairs the ability to regenerate a hair follicle. Remember that the sebaceous gland is located right there, and so the reduction in sebaceous glands is a key feature in moderate to advanced scarring alopecias. The sebaceous glands may still be there in the early, earliest stages, but reduction in sebaceous glands is key. These diseases are poorly understood. But presently, we classify them according to the infiltrate on biopsy. If there's a lot of lymphocytes, we group it as a lymphocyte-associated scarring alopecia. If there's a lot of neutrophils, it's a neutrophil-associated scarring alopecia.

And remember, we follow disease based on the symptoms, the signs, the shedding, and the sites. Those four S's. A photograph is extremely valuable to follow scarring alopecia. And without a photograph, I would find it very difficult myself to follow many of the patients in my practice with scarring alopecia. Remember that you cannot determine if a scarring alopecia is quiet the first time you meet a patient. But if you meet that patient and take a picture and look at that picture six, nine, twelve months later, and it's the same, there's a good chance that scarring alopecia is quiet.

And remember the other pearls we talked about for CCCA: any black woman with central hair loss needs to be considered to have CCCA until proven otherwise. Remember the dyspigmentation in discoid lupus. Remember the loss of the frontal hairline and the early loss of the eyebrows in frontal fibrosing alopecia. And remember that many of your patients with lichen planopilaris will present with central hair loss mimicking genetic hair loss, but they'll have burning and pain and itching. Their scalps will be tender. It's a biopsy which may help you confirm they have scarring alopecia.

So with that, I'd like to conclude. I want to thank you very much again for this invitation to speak to you today, and I'm very happy to answer any questions, both now or at any time later during the course of today. Thank you very much.