Alopecia Areata Clinical Case Review

Maryanne Senna, MD, assistant professor of dermatology at Harvard Medical School, introduces the case:

"Hi everyone. Thanks for joining us today for this discussion of a patient case of alopecia areata. My name is Maryanne Makredes Senna. I'm a board-certified dermatologist and hair loss specialist, and I run the Hair Loss Center of Excellence at Lahey Hospital Medical Center in Burlington, Massachusetts.

So, alopecia areata, as many of you may know, is a relatively prevalent autoimmune hair loss condition that leads to nonscarring hair loss. It globally affects two out of every 100 people, affects both sexes, and the initial onset typically occurs before age 30. And this schematic here shows where the inflammation occurs in alopecia areata. So, if we look at that top horizontal line, that’s the skin. And what we see diagonally coming out of the skin is the hair follicle. And the red dots at the bottom near the bulb or lowermost portion of the hair follicle are immune cells, namely cytotoxic T cells, that invade the hair follicle bulb leading to hair loss.

Now most commonly, patients with alopecia areata will present with one or several or many patches of discreet, usually round areas of hair loss on the scalp or other areas of the body. However in some cases, patients will have more severe forms of alopecia areata, like we see here in the middle, where there’s this ear-to-ear band of hair loss referred to as the ophiasis pattern, which can be very stubborn and resistant to treatment. Or, about 10% to 15% of patients who develop alopecia areata will go on to develop very severe alopecia areata, leading to complete loss of all scalp hair or even complete loss of all scalp and body hair, and this can include facial hair like eyebrows and eyelashes. So again, for a simplified overview of alopecia areata — and this will be important for later in the talk when we’re discussing potential treatment — what is happening under the skin is that these immune cells, namely cytotoxic Th1 T cells, go into the growing or antigen hair bulb, follicle bulb, and start an autoimmune attack. And this is against a still unrecognized antigen; we don’t know why this all starts out to begin with despite many years of research on this subject. Other immune cells, namely T helper cells, hover around in a peribulbar position. And we think that there could be some genetic, perhaps some environmental factors involved. But again, the exact trigger for this is unclear. And we know that a pathway referred to as the JAK-STAT pathway — or Janus kinase STAT pathway — plays a role in alopecia areata because we know that the inflammatory cells, those T-cells that attack the bulb of the hair follicle, release chemical signals called cytokines. And these cytokines involved in alopecia areata are ones like interferon gamma, IL-15, and they are key to perpetuating the inflammation in alopecia areata. The more cytokines, the more immune cells, the more inflammation, and then the cycle continues, more production of cytokines. And this constant perpetuation of inflammation is what leads to the hair continuing to be lost on the body or areas of the scalp. The cytokines like interferon gamma, IL-15, drive this continuous inflammation by activating these things called Janus kinases or JAKs on the immune cell surface. So, if we take one of these immune cells and blow it up, we see that there’s a JAK on the surface there. And when the cytokine binds to it, it actually leads to a continuous cycle of inflammation.

Moving on to sort of how we sort of think about this clinically — and we'll come back to why the JAK-STAT pathway is important again later on in the talk — we need to think about what is severe for alopecia areata. So, I think anyone watching this talk would say for sure that the patient all the way to the left is severe alopecia areata, right? The patient has no scalp hair at all. But what about the patient in the middle? This patient has an extensive area of hair loss. It is not complete. But you can see this patient is undergoing monthly very painful injections. You can see the welts on the scalp from where hundreds of injections have occurred here on this patient’s scalp. And if this patient isn’t responding to this treatment or having to have painful injections once a month lifelong, is that considered severe? What about the case on the right here of this person who has extensive loss in a very visible area, is that considered severe? And so, in order to come up with a consensus of what exactly is severe to help clinicians determine severity, a group of hair loss experts in the United States as well as industry collaborators came up with the alopecia areata scale. And this is something that can be used quickly in clinic. Basically, what the alopecia areata scale says is first determine about how much hair is missing on the scalp. Mild would be 20% or less scalp hair loss; moderate, 21 to 49% scalp hair loss; and 50% or more scalp hair loss is automatically severe. But those of us who see a lot of these patients understand that much more plays into how a patient experiences and how severe a disease is for that patient besides how much scalp hair is missing. And the things that we see that impact the disease include a negative impact on psychosocial functioning resulting from [alopecia areata].

So, you can imagine the patients with those more extensive areas, but not complete hair loss, they might have a difficult time doing their job if they’re public-facing in their role or having relationships or living life like the rest of us do. And this can be associated with significant anxiety and other psychosocial morbidities. There can be noticeable involvement of eyebrows or eyelashes, and until you don't have eyelashes, I think it’s difficult to really appreciate the functional role of eyelashes in keeping debris and airborne particles out of the eyes. But in addition, this can also add to making it more difficult for the patient to be able to hide their disease from the public. And this also can lead to significant psychosocial morbidity for a patient. Additionally, if a patient is not responding to a treatment after at least 6 months, or if you know that a patient is just rapidly progressing in front of you — they might have 20% hair, but they’re shedding hair at such a rapid rate that you know that they’re not going to have hair on their scalp — any one of these characteristics would take someone who is mild and raise them to moderate, or someone who is moderate and raise them to severe. So, the point is you start with scalp hair loss as a starting point; however, you want to factor in these other clinical things in thinking about how severe a case of alopecia areata might be."